subject:(GABAA receptor)

Vanderbilt University

1. Tian, Mengnan. Functional characterization of epilepsy associated GABRG2 mutations.

Degree: PhD, Pharmacology, 2012, Vanderbilt University

► Mutations in inhibitory GABAA receptor γ2 subunit gene, GABRG2, have been associated with genetic epilepsy syndromes including childhood absence epilepsy (CAE), pure febrile seizures (FS),… (more)

Subjects/Keywords: trafficking; GABAA receptor; GABRG2; epilepsy

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APA (6^th Edition):

Tian, M. (2012). Functional characterization of epilepsy associated GABRG2 mutations. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12274

Chicago Manual of Style (16^th Edition):

Tian, Mengnan. “Functional characterization of epilepsy associated GABRG2 mutations.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021. http://hdl.handle.net/1803/12274.

MLA Handbook (7^th Edition):

Tian, Mengnan. “Functional characterization of epilepsy associated GABRG2 mutations.” 2012. Web. 20 Jan 2021.

Vancouver:

Tian M. Functional characterization of epilepsy associated GABRG2 mutations. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1803/12274.

Council of Science Editors:

Tian M. Functional characterization of epilepsy associated GABRG2 mutations. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/12274

Vanderbilt University

2. Shen, Dingding. Characterization of GABAA receptor subunit mutations associated with epileptic encephalopathies.

Degree: PhD, Neuroscience, 2017, Vanderbilt University

URL: http://hdl.handle.net/1803/14271

► Epileptic encephalopathies (EEs) are a devastating group of severe childhood onset epilepsies with medication resistant seizures and poor developmental outcomes. Many EEs have a genetic… (more)

Subjects/Keywords: Epileptic encephalopathies; GABAA receptor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shen, D. (2017). Characterization of GABAA receptor subunit mutations associated with epileptic encephalopathies. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14271

Chicago Manual of Style (16^th Edition):

Shen, Dingding. “Characterization of GABAA receptor subunit mutations associated with epileptic encephalopathies.” 2017. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021. http://hdl.handle.net/1803/14271.

MLA Handbook (7^th Edition):

Shen, Dingding. “Characterization of GABAA receptor subunit mutations associated with epileptic encephalopathies.” 2017. Web. 20 Jan 2021.

Vancouver:

Shen D. Characterization of GABAA receptor subunit mutations associated with epileptic encephalopathies. [Internet] [Doctoral dissertation]. Vanderbilt University; 2017. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1803/14271.

Council of Science Editors:

Shen D. Characterization of GABAA receptor subunit mutations associated with epileptic encephalopathies. [Doctoral Dissertation]. Vanderbilt University; 2017. Available from: http://hdl.handle.net/1803/14271

Texas A&M University

3. Carver, Chase M. Role of Delta Subunit-Containing GABAA Receptors in Hippocampus Tonic Inhibition and Epileptogenesis within Transgenic Mouse Models.

Degree: PhD, Medical Sciences, 2015, Texas A&M University

URL: http://hdl.handle.net/1969.1/155155

► Epilepsy is associated with marked alterations in the structure and function of GABAA receptors in the hippocampus, a key structure for the genesis of epilepsy.… (more)

▼ Epilepsy is associated with marked alterations in the structure and function of GABAA receptors in the hippocampus, a key structure for the genesis of epilepsy. Two types of inhibition are mediated via distinct GABAA receptors. Phasic inhibition results from the synaptic γ2-containing receptors, whereas tonic inhibition is primarily mediated by the continuous activation of δ-containing, extrasynaptic receptors by ambient GABA present in the extracellular fluid. The δ-subunit receptors exhibit greater sensitivity to neurosteroid potentiation through positive allosteric modulation. The abundance of δ-subunit and the extent of tonic inhibition are altered by physiological and pathological neuroendocrine conditions. However, the precise functional impact of δ-subunit on inhibition in the hippocampus and epileptogenesis remain poorly understood. The main objective of this dissertation research was to understand the role of δ-subunit-containing GABAA receptors in the hippocampus dentate gyrus in mediation of tonic inhibition and epileptogenesis using a combination of electrophysiological, behavioral, and pharamcological techniques. We sought to understand the contribution of δ subunit to GABAergic inhibition and network excitability. We incorporated a perimenstrual model of catamenial epilepsy in which female mice experience acute neurosteroid withdrawal. The correlates of receptor plasticity and function were then examined. Furthermore, the structure-activity relationship of neurosteroids at extrasynaptic GABAA receptors was investigated in conducting the tonic inhibition. Alterations to hippocampus epileptogenesis of the δ-subunit knockout mouse as a model for hyperexcitability and susceptibility to seizures was also explored. Overall, these studies reveal a unique and novel role for δ-subunit-containing GABAA receptors as key modulators of tonic inhibition and excitability in the brain. These extrasynaptic receptors may represent new therapeutic targets for the control of epileptic conditions. Advisors/Committee Members: Reddy, Doodipala S (advisor), Rimer, Mendell (committee member), Griffith, William H (committee member), Zimmer, Warren (committee member).

Subjects/Keywords: GABAA receptor; neurosteroid; epilepsy; inhibition; electrophysiology

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APA (6^th Edition):

Carver, C. M. (2015). Role of Delta Subunit-Containing GABAA Receptors in Hippocampus Tonic Inhibition and Epileptogenesis within Transgenic Mouse Models. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/155155

Chicago Manual of Style (16^th Edition):

Carver, Chase M. “Role of Delta Subunit-Containing GABAA Receptors in Hippocampus Tonic Inhibition and Epileptogenesis within Transgenic Mouse Models.” 2015. Doctoral Dissertation, Texas A&M University. Accessed January 20, 2021. http://hdl.handle.net/1969.1/155155.

MLA Handbook (7^th Edition):

Carver, Chase M. “Role of Delta Subunit-Containing GABAA Receptors in Hippocampus Tonic Inhibition and Epileptogenesis within Transgenic Mouse Models.” 2015. Web. 20 Jan 2021.

Vancouver:

Carver CM. Role of Delta Subunit-Containing GABAA Receptors in Hippocampus Tonic Inhibition and Epileptogenesis within Transgenic Mouse Models. [Internet] [Doctoral dissertation]. Texas A&M University; 2015. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1969.1/155155.

Council of Science Editors:

Carver CM. Role of Delta Subunit-Containing GABAA Receptors in Hippocampus Tonic Inhibition and Epileptogenesis within Transgenic Mouse Models. [Doctoral Dissertation]. Texas A&M University; 2015. Available from: http://hdl.handle.net/1969.1/155155

University of Toronto

4. To, William T.H. Systemic Inflammation Increases the Efficacy of Anesthetics that Target GABAA Receptors.

Degree: 2013, University of Toronto

URL: http://hdl.handle.net/1807/69763

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Systemic inflammation markedly increases the neurodepressive properties of general anesthetics, for reasons that have remained poorly understood. The pro-inflammatory cytokine interleukin-1 beta (IL-1β) increases the… (more)

Subjects/Keywords: anesthesia; neuroscience; GABAA receptor; inflammation; 0317

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

To, W. T. H. (2013). Systemic Inflammation Increases the Efficacy of Anesthetics that Target GABAA Receptors. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/69763

Chicago Manual of Style (16^th Edition):

To, William T H. “Systemic Inflammation Increases the Efficacy of Anesthetics that Target GABAA Receptors.” 2013. Masters Thesis, University of Toronto. Accessed January 20, 2021. http://hdl.handle.net/1807/69763.

MLA Handbook (7^th Edition):

To, William T H. “Systemic Inflammation Increases the Efficacy of Anesthetics that Target GABAA Receptors.” 2013. Web. 20 Jan 2021.

Vancouver:

To WTH. Systemic Inflammation Increases the Efficacy of Anesthetics that Target GABAA Receptors. [Internet] [Masters thesis]. University of Toronto; 2013. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1807/69763.

Council of Science Editors:

To WTH. Systemic Inflammation Increases the Efficacy of Anesthetics that Target GABAA Receptors. [Masters Thesis]. University of Toronto; 2013. Available from: http://hdl.handle.net/1807/69763

5. Garcia, Tayllon dos Anjos. Envolvimento de vias mediadas por endocanabinoides na modulação do comportamento de defesa induzido pelo bloqueio de receptores GABAA na divisão dorso-medial do hipotálamo ventro-medial: papel do receptor CB1.

Degree: Mestrado, Farmacologia, 2014, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/17/17133/tde-21032014-173659/ ;

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Os efeitos dos canabinoides em algumas áreas encefálicas que expressam receptores endocanabinoides, como é o caso dos núcleos hipotalâmicos, não são ainda muito bem definidos.… (more)

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Os efeitos dos canabinoides em algumas áreas encefálicas que expressam receptores endocanabinoides, como é o caso dos núcleos hipotalâmicos, não são ainda muito bem definidos. Vários estudos têm demonstrado o papel de alguns núcleos hipotalâmicos na organização das reações induzidas pelo medo inato e pelo pânico. As respostas de defesa induzidas pelo medo instintivo caracterizam-se por serem mais elaboradas e dirigidas para algum abrigo ou rota de fuga. O estado de pânico pode ser provocado experimentalmente em animais de laboratório através da diminuição da atividade do sistema GABAérgico. O objetivo deste trabalho foi estudar os padrões comportamentais de fuga elaborada induzidos pelo bloqueio de receptores GABAérgicos do tipo A, com microinjeções intra-hipotalâmicas de bicuculina (BIC), especificamente na divisão dorso-medial do hipotálamo ventro-medial (VMHDM), assim como estabelecer o envolvimento endocanabinoides e o papel do receptor canabinoide do tipo 1 (CB1) na modulação das respostas defensivas organizadas pelo hipotálamo medial. Os resultados mostraram que a administração prévia de doses intermediárias (5pmol) de anandamida (AEA) atenuaram as respostas defensivas induzidas pela microinjeção intra-VMHDM de bicuculina (40ng), efeito este prevenido pelo pré-tratamento intra-hipotalâmica com antagonista de receptores CB1. Os resultados indicam que a AEA pode modular os efeitos pró-aversivos da bicuculina no VMHDM por meio do recrutamento de receptores CB1.

The effects of cannabinoids in some brain areas that express endocannabinoid receptors, such as some hypothalamic nuclei, are not yet well known. Several studies have demonstrated a role of hypothalamic nuclei in the organisation of behavioural responses induced by innate fear and panic attacks. The defensive responses induced by instinctive fear are more elaborated and oriented toward a burrow or alternative route of escape. Panic-prone states are able to be experimentally induced in laboratory animals decreasing the GABAergic system activity. The aim of this work was to study panic-like elaborated defensive behaviour evoked by GABAA receptor blockade with bicuculline (BIC) in the dorsomedial division of the ventromedial hypothalamus (VMHDM), we also aimed to establish the involvement of endocannabinoids and the role of CB1 cannabinoid receptor in the modulation of elaborated defense behavioural responses organised by medial hypothalamus. The results showed that intra-hypothalamic administration of anandamide (AEA) at the intermediate dose (5pmol) attenuated defensive responses induced by intra-VMHDM microinjection of bicuculline (40ng). This effect, however, was prevented by the pre-treatment of VMHDM with the CB1 receptor antagonist AM251. These results indicate that AEA can modulate the pro-aversive effects of bicuculline into the VMHDM, recruiting CB1 receptors.

Advisors/Committee Members: Coimbra, Norberto Cysne.

Subjects/Keywords: Comportamento de defesa; Defensive behaviour; Endocanabinoides; Endocannabinoid; GABAA receptor; Hipotálamo ventro-medial; Receptor GABAA; Ventromedial hypothalamus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Garcia, T. d. A. (2014). Envolvimento de vias mediadas por endocanabinoides na modulação do comportamento de defesa induzido pelo bloqueio de receptores GABAA na divisão dorso-medial do hipotálamo ventro-medial: papel do receptor CB1. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/17/17133/tde-21032014-173659/ ;

Chicago Manual of Style (16^th Edition):

Garcia, Tayllon dos Anjos. “Envolvimento de vias mediadas por endocanabinoides na modulação do comportamento de defesa induzido pelo bloqueio de receptores GABAA na divisão dorso-medial do hipotálamo ventro-medial: papel do receptor CB1.” 2014. Masters Thesis, University of São Paulo. Accessed January 20, 2021. http://www.teses.usp.br/teses/disponiveis/17/17133/tde-21032014-173659/ ;.

MLA Handbook (7^th Edition):

Garcia, Tayllon dos Anjos. “Envolvimento de vias mediadas por endocanabinoides na modulação do comportamento de defesa induzido pelo bloqueio de receptores GABAA na divisão dorso-medial do hipotálamo ventro-medial: papel do receptor CB1.” 2014. Web. 20 Jan 2021.

Vancouver:

Garcia TdA. Envolvimento de vias mediadas por endocanabinoides na modulação do comportamento de defesa induzido pelo bloqueio de receptores GABAA na divisão dorso-medial do hipotálamo ventro-medial: papel do receptor CB1. [Internet] [Masters thesis]. University of São Paulo; 2014. [cited 2021 Jan 20]. Available from: http://www.teses.usp.br/teses/disponiveis/17/17133/tde-21032014-173659/ ;.

Council of Science Editors:

Garcia TdA. Envolvimento de vias mediadas por endocanabinoides na modulação do comportamento de defesa induzido pelo bloqueio de receptores GABAA na divisão dorso-medial do hipotálamo ventro-medial: papel do receptor CB1. [Masters Thesis]. University of São Paulo; 2014. Available from: http://www.teses.usp.br/teses/disponiveis/17/17133/tde-21032014-173659/ ;

6. Pham, Thu Ha. Mécanisme d'action antidépresseur rapide de la kétamine et de son principal métabolite (2R,6R)-hydroxynorkétamine : rôle de la balance excitation-inhibition chez la souris : Mechanism of the antidepressant-like effects of ketamine and its main metabolite (2R,6R)-hydroxynorketamine : role of the excitatory and inhibitory balance in mice.

Degree: Docteur es, Toxicologie, 2018, Université Paris-Saclay (ComUE)

URL: http://www.theses.fr/2018SACLS086

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Selon l'OMS, les troubles dépressifs majeurs (TDM) seront la 2ème cause d'incapacité dans le monde en 2020 et deviendront la 1ère en 2030. Les antidépresseurs… (more)

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Selon l'OMS, les troubles dépressifs majeurs (TDM) seront la 2ème cause d'incapacité dans le monde en 2020 et deviendront la 1ère en 2030. Les antidépresseurs classiques ont des effets thérapeutiques retardés et de nombreux patients sont résistants. La kétamine, antagoniste du récepteur N-methyl-D-aspartate (R-NMDA) du L-glutamate, possède un effet antidépresseur rapide chez les patients résistants à un traitement classique. Le mécanisme de cette activité étonnante n'est pas bien compris. En couplant la microdialyse intracérébrale à un test comportemental prédictif d'une activité antidépressive dans un modèle de souris BALB/cJ de phénotype anxieux, nous montrons que cette activité de la kétamine dépend de la balance excitation-inhibition entre les systèmes glutamate/R-NMDA et R-AMPA, GABA/R-GABAA, sérotonine du circuit cortex préfrontal/noyau du raphé. Nos résultats suggèrent également que ce serait la combinaison [kétamine-(2R,6R)-hydroxynorkétamine, son principal métabolite cérébral] qui porterait l'effet antidépresseur. Mes travaux de thèse contribuent à une meilleure compréhension de l'effet rapide antidépresseur de la kétamine.

According to the WHO, major depressive disorder (MDD) will be the second leading cause of disability in the world in 2020 and will become the first in 2030. Conventional antidepressant drugs have delayed therapeutic effects and many patients are resistant. Ketamine, an N-methyl-D-aspartate (NMDA-R) receptor antagonist of L-glutamate, exerts a rapid antidepressant effect in patients who are resistant to standard therapy. The mechanism of this amazing activity is not well understood. By coupling intracerebral microdialysis to a predictive behavioral test of antidepressant activity in a BALB/cJ mouse model with an anxious phenotype, we show that this ketamine activity is dependent on the excitation-inhibition balance between glutamate/NMDA-R and AMPA-R, GABA/GABAA-R, serotonin systems in the prefrontal cortex/raphe nucleus circuit. Our results also suggest that it would be the combination [ketamine-(2R,6R)-hydroxynorketamine, its main brain metabolite] that would carry the antidepressant effect. My thesis work pave the way for the development of new fast-acting antidepressant drugs.

Advisors/Committee Members: Gardier, Alain (thesis director).

Subjects/Keywords: Glutamate; Récepteur NMDA; Ketamine; Antidépresseur; (2R; 6R)-Hydroxynorkétamine; Récepteur GABAA; Glutamate; NMDA receptor; Ketamine; Antidepressant; (2R; 6R)-Hydroxynorketamine; GABAA receptor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pham, T. H. (2018). Mécanisme d'action antidépresseur rapide de la kétamine et de son principal métabolite (2R,6R)-hydroxynorkétamine : rôle de la balance excitation-inhibition chez la souris : Mechanism of the antidepressant-like effects of ketamine and its main metabolite (2R,6R)-hydroxynorketamine : role of the excitatory and inhibitory balance in mice. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2018SACLS086

Chicago Manual of Style (16^th Edition):

Pham, Thu Ha. “Mécanisme d'action antidépresseur rapide de la kétamine et de son principal métabolite (2R,6R)-hydroxynorkétamine : rôle de la balance excitation-inhibition chez la souris : Mechanism of the antidepressant-like effects of ketamine and its main metabolite (2R,6R)-hydroxynorketamine : role of the excitatory and inhibitory balance in mice.” 2018. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed January 20, 2021. http://www.theses.fr/2018SACLS086.

MLA Handbook (7^th Edition):

Pham, Thu Ha. “Mécanisme d'action antidépresseur rapide de la kétamine et de son principal métabolite (2R,6R)-hydroxynorkétamine : rôle de la balance excitation-inhibition chez la souris : Mechanism of the antidepressant-like effects of ketamine and its main metabolite (2R,6R)-hydroxynorketamine : role of the excitatory and inhibitory balance in mice.” 2018. Web. 20 Jan 2021.

Vancouver:

Pham TH. Mécanisme d'action antidépresseur rapide de la kétamine et de son principal métabolite (2R,6R)-hydroxynorkétamine : rôle de la balance excitation-inhibition chez la souris : Mechanism of the antidepressant-like effects of ketamine and its main metabolite (2R,6R)-hydroxynorketamine : role of the excitatory and inhibitory balance in mice. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2018. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2018SACLS086.

Council of Science Editors:

Pham TH. Mécanisme d'action antidépresseur rapide de la kétamine et de son principal métabolite (2R,6R)-hydroxynorkétamine : rôle de la balance excitation-inhibition chez la souris : Mechanism of the antidepressant-like effects of ketamine and its main metabolite (2R,6R)-hydroxynorketamine : role of the excitatory and inhibitory balance in mice. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2018. Available from: http://www.theses.fr/2018SACLS086

UCLA

7. Ferando, Isabella. Plasticity of GABAergic Inhibition.

Degree: Molec, Cell, & Integ Physiology, 2014, UCLA

URL: http://www.escholarship.org/uc/item/32b9h7ck

► &gamma-aminobtutyric acid (GABA) is a transmitter molecule found in several organs and virtually all organisms. In the vertebrate central nervous system it is the major… (more)

▼ &gamma-aminobtutyric acid (GABA) is a transmitter molecule found in several organs and virtually all organisms. In the vertebrate central nervous system it is the major inhibitory neurotransmitter. Here GABA released by GABAergic neurons binds to GABA receptors and regulates neuronal excitability, network synchrony and neuronal development. GABA_A receptors (GABA_ARs) are highly conserved ligand-gated ion channels permeable to Cl^- and HCO₃^-, and upon binding GABA they generate currents that can be functionally distinguished in phasic or tonic. Physiology of tonic GABAergic conductances is of particular interest as these exercise powerful constrain on neuronal excitability and gain. Tonic inhibition is mediated by GABA_ARs containing &delta or &alpha5 subunits localized outside of the synaptic cleft and activated by ambient GABA. Object of this dissertation is plasticity of &delta- GABA_ARs, as their function and distinct pharmacology makes them relevant to many human diseases. &delta-GABA_ARs are naturally insensitive to benzodiazepines while uniquely sensitive to low concentrations of neurosteroids, which act on them as positive allosteric modulators. These endogenous steroids are the neuroactive form of progesterone, cortisol and testosterone. They are locally synthetized in both neurons and glia and their brain concentration varies in parallel with oscillations in plasma precursors. The present work shows how during times of altered neurosteroid production &delta-GABA_ARs expression homeostatically changes with functional consequences on neuronal network functioning. In particular, plasticity of &delta-GABA_ARs during pregnancy and the postpartum affects hippocampal excitability and &gamma oscillations frequency in vitro. Moreover, over the ovarian cycle, plasticity of &delta-GABA_ARs on interneurons is necessary for fluctuations in &gamma oscillations amplitude in vivo. More and more evidence suggests an involvement of &delta-GABA_ARs in different kinds of neurological and psychiatric disorders, such as epilepsies, postpartum depression, pre-menstrual dysphoric disorder, and schizophrenia. Interestingly a convenient therapeutic strategy may be available, given the anatomical distribution of these receptors. In fact, &delta-GABA_ARs expressed on excitatory neurons of the cortex contain &alpha4 subunits, whereas on interneurons they contain &alpha1 subunits. This allows to pharmacologically differentiate &delta-GABA_ARs on specific neuron. Development of drugs optimized to selectively modify &delta-GABA_A-mediated tonic inhibition of excitatory or inhibitory neurons may lead to critical clinical applications.

Subjects/Keywords: Neurosciences; GABA; GABAA receptor; gamma oscillations; neurosteroids; pregnancy; tonic inhibition

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ferando, I. (2014). Plasticity of GABAergic Inhibition. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/32b9h7ck

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ferando, Isabella. “Plasticity of GABAergic Inhibition.” 2014. Thesis, UCLA. Accessed January 20, 2021. http://www.escholarship.org/uc/item/32b9h7ck.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ferando, Isabella. “Plasticity of GABAergic Inhibition.” 2014. Web. 20 Jan 2021.

Vancouver:

Ferando I. Plasticity of GABAergic Inhibition. [Internet] [Thesis]. UCLA; 2014. [cited 2021 Jan 20]. Available from: http://www.escholarship.org/uc/item/32b9h7ck.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ferando I. Plasticity of GABAergic Inhibition. [Thesis]. UCLA; 2014. Available from: http://www.escholarship.org/uc/item/32b9h7ck

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University

8. Satpute Janve, Vaishali. Epileptic encephalopathy associated human GABRB mutations disrupt GABAA receptor function and results in Lennox-Gastaut syndrome in Gabrb3+/D120N knock-in mice.

Degree: PhD, Neuroscience, 2019, Vanderbilt University

URL: http://hdl.handle.net/1803/11950

► Epileptic encephalopathies (EEs) are catastrophic childhood epilepsies with intractable seizures, developmental delays, and cognitive impairment. I determined the functional impact of five de novo GABAA… (more)

▼ Epileptic encephalopathies (EEs) are catastrophic childhood epilepsies with intractable seizures, developmental delays, and cognitive impairment. I determined the functional impact of five de novo GABAA receptor β subunit gene (GABRB) mutations identified in triads with a proband with one of two EEs⎯Infantile spasms (IS) and Lennox-Gastaut syndrome (LGS). In HEK293T cells, the major effects of the LGS-associated GABRB3(D120N, E180G, Y302C) mutations were reduced GABA-evoked currents due to reduced channel open probability and burst duration. While IS-associated GABRB3(N110D) and GABRB1(F246S) mutations altered current rise time and deactivation due to reduced channel open probability and burst duration for the GABRB3(N110D) mutation, and reduced channel conductance and opening frequency for the GABRB1(F246S) mutation. These alterations in GABAA receptor channel function should reduce neuronal inhibition, leading to seizures. Thus, these data provide strong evidence for a contribution of GABRB mutations to LGS and IS pathology. To understand the role of these mutations in vivo, we generated a knock-in mouse with the Gabrb3(D120N) mutation (Gabrb3+/D120N). I found that Gabrb3+/D120N mice had early onset epileptic spasms from P14-P17 and multiple types of seizures in adulthood including typical and atypical absence, myoclonic, tonic, and generalized tonic-clonic seizures. The predominant seizure type in adult Gabrb3+/D120N mice were absence seizures (~400/day), which are the characteristic seizures of LGS. The gabrb3+/D120N mouse is the first mouse model of LGS and the first mouse model with spontaneous atypical absence seizures and LGS behavioral comorbidities. Gabrb3+/D120N mice will aid in understanding the pathophysiology and treatment of LGS. Advisors/Committee Members: Dr. Robert L. Macdonald (committee member), Dr. Andre H. Lagrange (committee member), Dr. Jennifer A. Kearney (committee member), Dr. Jerod S. Denton (committee member), Dr. Bruce D. Carter (Committee Chair).

Subjects/Keywords: mouse model; pediatric; Epilepsy; GABAA receptor mutations; Lennox-Gastaut syndrome

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Satpute Janve, V. (2019). Epileptic encephalopathy associated human GABRB mutations disrupt GABAA receptor function and results in Lennox-Gastaut syndrome in Gabrb3+/D120N knock-in mice. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11950

Chicago Manual of Style (16^th Edition):

Satpute Janve, Vaishali. “Epileptic encephalopathy associated human GABRB mutations disrupt GABAA receptor function and results in Lennox-Gastaut syndrome in Gabrb3+/D120N knock-in mice.” 2019. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021. http://hdl.handle.net/1803/11950.

MLA Handbook (7^th Edition):

Satpute Janve, Vaishali. “Epileptic encephalopathy associated human GABRB mutations disrupt GABAA receptor function and results in Lennox-Gastaut syndrome in Gabrb3+/D120N knock-in mice.” 2019. Web. 20 Jan 2021.

Vancouver:

Satpute Janve V. Epileptic encephalopathy associated human GABRB mutations disrupt GABAA receptor function and results in Lennox-Gastaut syndrome in Gabrb3+/D120N knock-in mice. [Internet] [Doctoral dissertation]. Vanderbilt University; 2019. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1803/11950.

Council of Science Editors:

Satpute Janve V. Epileptic encephalopathy associated human GABRB mutations disrupt GABAA receptor function and results in Lennox-Gastaut syndrome in Gabrb3+/D120N knock-in mice. [Doctoral Dissertation]. Vanderbilt University; 2019. Available from: http://hdl.handle.net/1803/11950

Vanderbilt University

9. Tang, Xin. Modulation of GABAA receptor function by PKA and PKC protein phosphorylation.

Degree: PhD, Neuroscience, 2010, Vanderbilt University

URL: http://hdl.handle.net/1803/11843

► We studied the modulation of ¦Á4¦Â3¦Ã2L and ¦Á4¦Â3¦Ä GABAA receptor currents by two protein kinases, PKA and PKC. Although modulation of synaptic ¦Á1¦Â¦Ã2 GABAA receptor… (more)

Subjects/Keywords: PKC; GABAA receptor; phosphorylation; PKA

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tang, X. (2010). Modulation of GABAA receptor function by PKA and PKC protein phosphorylation. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11843

Chicago Manual of Style (16^th Edition):

Tang, Xin. “Modulation of GABAA receptor function by PKA and PKC protein phosphorylation.” 2010. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021. http://hdl.handle.net/1803/11843.

MLA Handbook (7^th Edition):

Tang, Xin. “Modulation of GABAA receptor function by PKA and PKC protein phosphorylation.” 2010. Web. 20 Jan 2021.

Vancouver:

Tang X. Modulation of GABAA receptor function by PKA and PKC protein phosphorylation. [Internet] [Doctoral dissertation]. Vanderbilt University; 2010. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1803/11843.

Council of Science Editors:

Tang X. Modulation of GABAA receptor function by PKA and PKC protein phosphorylation. [Doctoral Dissertation]. Vanderbilt University; 2010. Available from: http://hdl.handle.net/1803/11843

Univerzitet u Beogradu

10. Joksimović, Srđan M., 1981-. Značaj modulacije pojedinih podtipova benzodiazepinskog mesta vezivanja GABAA receptora za ispoljavanje bihejvioralnih efekata benzodiazepina.

Degree: Farmaceutski fakultet, 2015, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:7659/bdef:Content/get

►

Farmacija - Farmakologija / Pharmacy - Pharmacology

Ubrzo nakon otkrića supstanci benzodiazepinske strukture 60–tih godina prošlog veka, diazepam je postao jedan od najpropisivanijih lekova (Valium®).… (more)

▼

Farmacija - Farmakologija / Pharmacy - Pharmacology

Ubrzo nakon otkrića supstanci benzodiazepinske strukture 60–tih godina prošlog veka, diazepam je postao jedan od najpropisivanijih lekova (Valium®). Međutim, iako i dalje vrlo popularni lekovi, benzodiazepini se u modernoj kliničkoj praksi propisuju sa mnogo više predostrožnosti, što se može povezati sa pojavom novijih terapijskih alternativa, ali i ne tako povoljnog bezbednosnog profila. Svi benzodiazepini koji se nalaze u kliničkoj upotrebi su neselektivni pozitivni alosterni modulatori benzodiazepinskog mesta vezivanja GABAA receptora. Ovo vezno mesto se nalazi na međupovršini između α i γ2 podjedinice GABAA receptora, koji se najčešće sastoji od 1 γ, 2 β i 2 α (α1, α2, α3 ili α5) podjedinice. Benzodiazepini, primenjeni akutno, ispoljavaju sedativni, hipnotički, anksiolitički, antikonvulzivni, miorelaksantni i amnezijski efekat u eksperimentalnih životinja i ljudi. Višekratna primena benzodiazepina može dovesti do fizičke zavisnosti tako da se po prekidu terapije mogu pojaviti znaci sindroma obustave, a poznato je i da ovi lekovi mogu biti lekovi zloupotrebe. Komparabilan afinitet i značajna potencijacija sva četiri podtipa GABAA receptora zaslužni su za ovako širok spektar delovanja benzodiazepina. Svi ovi nedostaci uticali su na smanjenje kliničke upotrebe benzodiazepina, ali su istovremeno inspirisali razvoj supstanci selektivnih za pojedine podtipove GABAA receptora – od kojih potencijalno najveći terapijski značaj imaju anksioselektivni anksiolitici – čime bi se postiglo razdvajanje željenih od neželjenih efekata. Razvoj selektivnih liganada se u velikoj meri oslanjao na rezultate studija na genetski modifikovanim miševima, koji su jasno ukazali na vezu između pojedinih podtipova GABAA receptora i različitih efekata benzodiazepina. Tako su sedativni, amnezijski, ataksični i delom antikonvulzivni efekat diazepama pripisani populaciji α1 GABAA receptora, anksiolitički α2–, a u određenim okolnostima i α3 GABAA receptorima, u posredovanju miorelaksantnog efekta učestvuju α2/α3/α5 GABAA receptori, dok su za uticaj na određene memorijske procese odgovorni GABAA receptori koji sadrže α5 podjedinicu..

Advisors/Committee Members: Savić, Miroslav, 1973-.

Subjects/Keywords: benzodiazepines; subtype–selective ligands; GABAA receptor; behavior; Wistar rat

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Joksimović, Srđan M., 1. (2015). Značaj modulacije pojedinih podtipova benzodiazepinskog mesta vezivanja GABAA receptora za ispoljavanje bihejvioralnih efekata benzodiazepina. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:7659/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Joksimović, Srđan M., 1981-. “Značaj modulacije pojedinih podtipova benzodiazepinskog mesta vezivanja GABAA receptora za ispoljavanje bihejvioralnih efekata benzodiazepina.” 2015. Thesis, Univerzitet u Beogradu. Accessed January 20, 2021. https://fedorabg.bg.ac.rs/fedora/get/o:7659/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Joksimović, Srđan M., 1981-. “Značaj modulacije pojedinih podtipova benzodiazepinskog mesta vezivanja GABAA receptora za ispoljavanje bihejvioralnih efekata benzodiazepina.” 2015. Web. 20 Jan 2021.

Vancouver:

Joksimović, Srđan M. 1. Značaj modulacije pojedinih podtipova benzodiazepinskog mesta vezivanja GABAA receptora za ispoljavanje bihejvioralnih efekata benzodiazepina. [Internet] [Thesis]. Univerzitet u Beogradu; 2015. [cited 2021 Jan 20]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:7659/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Joksimović, Srđan M. 1. Značaj modulacije pojedinih podtipova benzodiazepinskog mesta vezivanja GABAA receptora za ispoljavanje bihejvioralnih efekata benzodiazepina. [Thesis]. Univerzitet u Beogradu; 2015. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:7659/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Dundee

11. Humble, Stephen R. Neurosteroids : endogenous analgesics?.

Degree: Thesis (D.Sc.), 2013, University of Dundee

URL: https://discovery.dundee.ac.uk/en/studentTheses/c4659466-cd41-494d-aec6-edcf50e5274b ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.578936

► Peripheral sensitisation and central sensitisation are implicated in the development of neuropathic pain with neuroplasticity occurring at multiple levels of the pain pathway. Hypersensitivity of… (more)

▼ Peripheral sensitisation and central sensitisation are implicated in the development of neuropathic pain with neuroplasticity occurring at multiple levels of the pain pathway. Hypersensitivity of the spinothalamic tract has been described in neuropathic animal models of diabetes. Spinal dorsal horn neurones of diabetic rats exhibit abnormally high spontaneous firing, suggesting an imbalance between excitatory and inhibitory signals converging within this structure. GABAergic neurones within the spinal cord and thalamus are crucial for the transmission of painful stimuli to higher centres of the brain that are involved in pain perception. GABAA receptors (GABAARs) are an important target for many clinical drugs, and certain endogenous neurosteroids act as potent allosteric modulators of these receptors. A developmental change in the rate of exponential decay of GABAergic synaptic events has been observed in other types of neurones and this may be related in part to fluctuations in endogenous neurosteroid tone. The objective of this study was to investigate changes to inhibitory neurotransmission with development in three levels of the pain pathway and to explore potential mechanisms underlying diabetic neuropathy. The whole-cell patch-clamp technique was used on slices of neural tissue. Electrophysiological recordings were obtained from wild type mice between the ages of 6 and 80 days in lamina II of the spinal cord, the nucleus reticularis (nRT) of the thalamus and the cerebral cortex. Recordings were also obtained from mice with diabetic neuropathy (ob/ob and db/db) between the ages of 60 and 80 days. Neurosteroids and their precursors were employed along with compounds that prevented their activity at the GABAAR such as ?-cyclodextrin, which is a barrel-shaped cyclic oligosaccharide with a lipophilic interior that sequesters neurosteroids. Behavioural experiments were also performed using von Frey filaments and the tail flick test to examine mechanical and thermal nociception. Recordings from the spinal cord, the thalamus and the cerebral cortex revealed that the decay time of miniature inhibitory postsynaptic currents are significantly reduced with development. The neurosteroids allopregnanolone and ganaxolone were significantly more effective in neurones from the older mice. In contrast, ?-cyclodextrin had significantly less effect in neurones from the older mice. In mature diabetic mice (ob/ob mice), the endogenous neurosteroid tone is reduced compared to control mice, but certain neurosteroid compounds have a greater effect on the GABAARs of these diabetic mice. In addition, the diabetic mice exhibit mechanical allodynia and hyperalgesia, which is responsive to exogenously applied neurosteroids. These results are consistent with the hypothesis that a dramatic reduction in endogenous neurosteroid tone occurs as development progresses and that this impacts on the exponential decay time of GABAergic mIPSCs within neurones of the pain pathway. The higher neurosteroid tone in the youngest mice may confer a degree of…

Subjects/Keywords: 612.8; Neurosteroids; Neuropathic pain; Diabetic neuropathy; GABAA receptor; GABAAR

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Humble, S. R. (2013). Neurosteroids : endogenous analgesics?. (Doctoral Dissertation). University of Dundee. Retrieved from https://discovery.dundee.ac.uk/en/studentTheses/c4659466-cd41-494d-aec6-edcf50e5274b ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.578936

Chicago Manual of Style (16^th Edition):

Humble, Stephen R. “Neurosteroids : endogenous analgesics?.” 2013. Doctoral Dissertation, University of Dundee. Accessed January 20, 2021. https://discovery.dundee.ac.uk/en/studentTheses/c4659466-cd41-494d-aec6-edcf50e5274b ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.578936.

MLA Handbook (7^th Edition):

Humble, Stephen R. “Neurosteroids : endogenous analgesics?.” 2013. Web. 20 Jan 2021.

Vancouver:

Humble SR. Neurosteroids : endogenous analgesics?. [Internet] [Doctoral dissertation]. University of Dundee; 2013. [cited 2021 Jan 20]. Available from: https://discovery.dundee.ac.uk/en/studentTheses/c4659466-cd41-494d-aec6-edcf50e5274b ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.578936.

Council of Science Editors:

Humble SR. Neurosteroids : endogenous analgesics?. [Doctoral Dissertation]. University of Dundee; 2013. Available from: https://discovery.dundee.ac.uk/en/studentTheses/c4659466-cd41-494d-aec6-edcf50e5274b ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.578936

University of Toronto

12. Hogg, David William. GABA Receptor and KCa Channel-mediated Electrical Suppression in Anoxic Cortical Pyramidal Neurons of the Painted Turtle (Chrysemys picta bellii).

Degree: PhD, 2015, University of Toronto

URL: http://hdl.handle.net/1807/69268

► The high energetic cost of neuronal communication requires large amounts of ATP to maintain function. In mammals, oxidative phosphorylation is required to meet these energy… (more)

▼ The high energetic cost of neuronal communication requires large amounts of ATP to maintain function. In mammals, oxidative phosphorylation is required to meet these energy demands and without sufficient oxygen supply neuronal hyperexcitability and excitotoxic cell death occurs. This catastrophic cascade of events does not happen in the freshwater painted turtle Chrysemys picta bellii, instead there is a coordinated downregulation of cellular ATP consuming processes to match the lower anaerobic ATP supply. To reduce the energetic burden during anoxia turtles have evolved a sophisticated network of neuroprotective mechanisms including channel arrest and spike arrest which combine to prevent membrane depolarization and activation of excessive electrical activity. The aim of my research was to identify and elucidate cellular mechanisms responsible for suppression of electrical activity in anoxic turtle dorsal cortical brain pyramidal neurons. Using electrophysiological and fluorescent imaging techniques I demonstrate for the first time that: 1) in turtle dorsal cortex gamma-aminobutyric acid (GABA) release increases during anoxia and enhances a unique GABAA receptor-mediated giant postsynaptic current, and shifts membrane potential to the GABA reversal potential (EGABA), reducing electrical excitability; 2) endogenous GABAergic mechanisms responsible for anoxia-tolerance also protect against a debilitating ischemic solution that mimics the cerebral fluid in the penumbral area that surrounds the infarct core; 3) in pyramidal neurons the open probability of Ca2+-activated K+ channels decreases during anoxia and this is prevented by inhibition of protein kinase C; and 4) anoxia-mediated decreases in mitochondrial reactive oxygen species (ROS) production are sufficient to initiate a redox-sensitive inhibitory GABA signaling cascade that suppresses electrical activity. Together this research significantly contributes to our understanding of the turtle's natural anoxia-tolerant strategy in brain and highlights the integral role of channel arrest and GABAergic spike arrest in prevention of anoxic or ischemic cell damage Advisors/Committee Members: Buck, Leslie T, Cell and Systems Biology.

Subjects/Keywords: Anoxia; Channel arrest; GABAA receptor; Pyramidal neuron; Spike arrest; Turtle; 0317

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hogg, D. W. (2015). GABA Receptor and KCa Channel-mediated Electrical Suppression in Anoxic Cortical Pyramidal Neurons of the Painted Turtle (Chrysemys picta bellii). (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/69268

Chicago Manual of Style (16^th Edition):

Hogg, David William. “GABA Receptor and KCa Channel-mediated Electrical Suppression in Anoxic Cortical Pyramidal Neurons of the Painted Turtle (Chrysemys picta bellii).” 2015. Doctoral Dissertation, University of Toronto. Accessed January 20, 2021. http://hdl.handle.net/1807/69268.

MLA Handbook (7^th Edition):

Hogg, David William. “GABA Receptor and KCa Channel-mediated Electrical Suppression in Anoxic Cortical Pyramidal Neurons of the Painted Turtle (Chrysemys picta bellii).” 2015. Web. 20 Jan 2021.

Vancouver:

Hogg DW. GABA Receptor and KCa Channel-mediated Electrical Suppression in Anoxic Cortical Pyramidal Neurons of the Painted Turtle (Chrysemys picta bellii). [Internet] [Doctoral dissertation]. University of Toronto; 2015. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1807/69268.

Council of Science Editors:

Hogg DW. GABA Receptor and KCa Channel-mediated Electrical Suppression in Anoxic Cortical Pyramidal Neurons of the Painted Turtle (Chrysemys picta bellii). [Doctoral Dissertation]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/69268

Penn State University

13. Wu, Xia. Targeting and function of extrasynaptic GABAA receptors.

Degree: 2012, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/16080

► γ-aminobutyric acid type-A receptors (GABAARs) are localized at both synaptic and extrasynaptic sites, mediating phasic and tonic inhibition, respectively. Although the targeting mechanism of synaptic… (more)

▼ γ-aminobutyric acid type-A receptors (GABAARs) are localized at both synaptic and extrasynaptic sites, mediating phasic and tonic inhibition, respectively. Although the targeting mechanism of synaptic GABAA receptors has been extensively studied, the exact mechanism underlying extrasynaptic GABAA-receptor targeting was not known. The primary objective of this thesis was to elucidate the targeting mechanisms for distinct GABAA receptors, with special focus on the extrasynaptic GABAA receptors. Previous studies suggest an important role of γ2 and δ subunits in synaptic versus extrasynaptic targeting of GABAARs. Here, we demonstrate differential function of α2 and α6 subunits in guiding the localization of GABAARs. To study the targeting of specific subtypes of GABAARs, we used a molecularly engineered GABAergic synapse model to precisely control the GABAA-R subunit composition. We found that in neuron-HEK cell heterosynapses, GABAergic events mediated by α2β3γ2 receptors were very fast (rise time ~2 ms), whereas events mediated by α6β3δ receptors were very slow (rise time ~20 ms). Such an order of magnitude difference in rise time could not be attributed to the minute differences in receptor kinetics. Interestingly, synaptic events mediated by α6β3 or α6β3γ2 receptors were significantly slower than those mediated by α2β3 or α2β3γ2 receptors, suggesting a differential role of α subunit in receptor targeting. This was confirmed by differential targeting of the same δ-γ2 chimeric subunits to synaptic or extrasynaptic sites, depending on whether it was co-assembled with the α2 or α6 subunit. In addition, insertion of a gephyrin-binding site into the intracellular domain of α6 and δ subunits brought α6β3δ receptors closer to synaptic sites. Therefore, the α subunits, together with the γ2 and δ subunits, play a critical role in governing synaptic versus extrasynaptic targeting of GABAARs, possibly through differential interactions with gephyrin. For the second part of this thesis, I investigated the functional interaction between synaptic and extrasynaptic GABAA receptors. Our data showed that ectopically expressing extrasynaptic α6β3δ-receptors in mouse pyramidal neurons significantly increased tonic currents, as expected. Surprisingly, the increase of tonic inhibition was accompanied with a substantial reduction of the fast synaptic GABAergic transmission, suggesting a possible homeostatic regulation of the total inhibition. Overexpressing the α6 subunit alone induced an upregulation of the δ subunit expression level, and suppressed phasic inhibition similar to that with α6β3δ subunits. Blocking all GABAA receptors after overexpressing α6β3δ subunits did not restore the level of synaptic GABAergic transmission, suggesting that receptor activation is not required for the interplay between synaptic and extrasynaptic GABAA receptors. Furthermore, insertion of a gephyrin-binding-site (GBS) into the intracellular loop of α6 and δ subunits recruited α6GBSβ3δGBS-receptors to postsynaptic sites, but failed to rescue synaptic… Advisors/Committee Members: Gong Chen, Dissertation Advisor/Co-Advisor, Bernhard Luscher, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Timothy J Jegla, Committee Member, Bruce Gluckman, Special Member.

Subjects/Keywords: extrasynaptic GABAA receptor; targeting; tonic inhibition; gephyrin; alpha subunit; delta subunit; homeostatic regulation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wu, X. (2012). Targeting and function of extrasynaptic GABAA receptors. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/16080

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wu, Xia. “Targeting and function of extrasynaptic GABAA receptors.” 2012. Thesis, Penn State University. Accessed January 20, 2021. https://submit-etda.libraries.psu.edu/catalog/16080.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wu, Xia. “Targeting and function of extrasynaptic GABAA receptors.” 2012. Web. 20 Jan 2021.

Vancouver:

Wu X. Targeting and function of extrasynaptic GABAA receptors. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Jan 20]. Available from: https://submit-etda.libraries.psu.edu/catalog/16080.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wu X. Targeting and function of extrasynaptic GABAA receptors. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/16080

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Ottawa

14. Mullally, Martha. Anxiety-Reducing Tropical Plants: Phytochemical and Pharmacological Characterization of Souroubea sympetala and Piper amalago .

Degree: 2011, University of Ottawa

URL: http://hdl.handle.net/10393/20379

► This thesis investigates the phytochemistry and pharmacology of two neotropical plants used traditionally to treat anxiety and stress, Souroubea sympetala (Marcgraviaceae) and Piper amalago (Piperaceae).… (more)

▼ This thesis investigates the phytochemistry and pharmacology of two neotropical plants used traditionally to treat anxiety and stress, Souroubea sympetala (Marcgraviaceae) and Piper amalago (Piperaceae). A method of phytochemical analysis was developed to characterize S. sympetala extracts, identifying and quantifying four triterpenes, which were present in higher amounts in bark as compared to leaf. Subsequently, a standardized supercritical CO2 extraction procedure for S. sympetala was developed and compared favourably with conventional extraction methods in terms of its anxiety-reducing effects in a behavioural assay of anxiety and content of the active principle, betulinic acid (BA). All of these materials demonstrated anxiolytic properties. The pharmacological mode of action of S. sympetala raw plant, extracts and isolated active principle were examined in rodent behavioural models of anxiety. The extracts were shown to have affinity for the γ-amino butyric acid (GABA)a benzodiazepine (GABAa- BZD) receptor of the central nervous system in vitro, in a competitive binding assay. Pre-treatment of animals with the GABAa-BZD antagonist flumazenil, followed by plant extract and pure compound extinguished the anxiety-reducing effect, demonstrating that S. sympetala and BA act at the GABAa- BZD receptor in vivo. The effect of S. sympetala in stressed animals, specifically its cortisol-lowering ability was investigated in vitro and in vivo in rainbow trout. Both leaf extract and BA significantly lowered cortisol in response to an adrenocorticotropic hormone (ACTH) challenge in vitro and a standardized net restraint assay in vivo. The anxiety-reducing effect of P. amalago was examined and the bioactive principle identified by bioassay-guided fractionation. P. amalago extract significantly reduced anxiety-like behaviour in rats and demonstrated affinity for the GABAa-BZD receptor in vitro. The bioactive molecule was determined to be a furofuran lignan. Together these results provide a pharmacological basis for the traditional use of S. sympetala and P. amalago to treat anxiety and elucidate their mode of action and active principles. S. sympetala is now thoroughly characterized and represents an excellent candidate plant for development as a natural health product.

Subjects/Keywords: Piper amalago; Souroubea sympetala; GABAa-BZD receptor; ethnopharmacology; ethnobotany; anxiolysis; anxiety; GABA

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mullally, M. (2011). Anxiety-Reducing Tropical Plants: Phytochemical and Pharmacological Characterization of Souroubea sympetala and Piper amalago . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/20379

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mullally, Martha. “Anxiety-Reducing Tropical Plants: Phytochemical and Pharmacological Characterization of Souroubea sympetala and Piper amalago .” 2011. Thesis, University of Ottawa. Accessed January 20, 2021. http://hdl.handle.net/10393/20379.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mullally, Martha. “Anxiety-Reducing Tropical Plants: Phytochemical and Pharmacological Characterization of Souroubea sympetala and Piper amalago .” 2011. Web. 20 Jan 2021.

Vancouver:

Mullally M. Anxiety-Reducing Tropical Plants: Phytochemical and Pharmacological Characterization of Souroubea sympetala and Piper amalago . [Internet] [Thesis]. University of Ottawa; 2011. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10393/20379.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mullally M. Anxiety-Reducing Tropical Plants: Phytochemical and Pharmacological Characterization of Souroubea sympetala and Piper amalago . [Thesis]. University of Ottawa; 2011. Available from: http://hdl.handle.net/10393/20379

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Duke University

15. Tseng, Wei Chou. A Novel Function of Giant Ankyrin-G in Promoting the Formation of Somatodendritic GABAA Receptor Synaptogenesis .

Degree: 2014, Duke University

URL: http://hdl.handle.net/10161/9407

► The formation and retention of distinct membrane domains in the fluidic membrane bilayer is the key process in establishing spatial organization for mediating physiological… (more)

▼ The formation and retention of distinct membrane domains in the fluidic membrane bilayer is the key process in establishing spatial organization for mediating physiological functions in metazoans. The spectrin-ankyrin network organizes diverse membrane domains including T-tubule and intercalated disc of cardiomyocytes, basolateral membrane of epithelial cells, costameres of striatal muscle, and axon initial segments and nodes of Ranvier in nervous system. This thesis identifies a novel function of 480 kDa ankyrin-G, an alternatively spliced isoform of the ankyrin family, in promoting somatodendritic GABAA receptor synaptogenesis both in vitro and in vivo. In the nervous system, an insertion of a neuronal specific exon (exon 37) occurs in ankyrin-G polypeptide which results in a 480 kDa isoform. 480 kDa ankyrin-G (giant ankyrin-G) has been shown to coordinate formation and maintenance of the axon initial segment (AIS) and nodes of Ranvier. This thesis research began with the discovery that giant ankyrin-G, previously thought to be confined to the axon initial segment, forms developmentally-regulated and cell-type specific somatodendritic "outposts" on the plasma membrane of pyramidal neurons. This somatodendritic 480 kDa ankyrin-G outpost forms micron-scale membrane domains where it associates with canonical AIS binding partners including voltage-gated sodium channel and neurofascin. This thesis further discovered that the giant insert of 480 kDa ankyrin-G interacts with GABARAP, a GABAA receptor-associated protein. Both the interaction with GABARAP and the membrane association through palmitoylation of giant ankyrin-G are required for the formation of somatodendritic GABAergic synapses. This work further found that ankyrin-G associates with extrasynaptic GABAA receptors and stabilizes receptors on the extrasynaptic membrane through opposing endocytosis. This story demonstrates for the first time the existence of giant ankyrin-G somatodendritic outpost as well as its function in directing the formation of GABAergic synapses that provides a rationale for studies linking ankyrin-G genetic variation with psychiatric disease and neurodevelopmental disorders. Additional work presented in the Appendix characterized novel ankyrin-G full length transcripts in the heart and kidney with unique domain compositions though alternative splicing. The preliminary work further identified biochemical properties and potential role of an insert C in the C-terminus of ankyrin-G in mediating cytokinesis and cellular migration in mouse fibroblasts. Together, this thesis work expands the knowledge of giant ankyrin-G functions in the nervous system and offers insights into the diversified roles of distinct ankyrin-G peptides acquired from alternative splicing in organizing specific membrane domains and interacting with defined intracellular pathways in different tissues. Advisors/Committee Members: Bennett, Vann (advisor).

Subjects/Keywords: Biology; Neurosciences; extrasynaptic membrane; GABAA receptor endocytosis; GABAergic synapses; GABARAP; giant ankyrin-G

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APA (6^th Edition):

Tseng, W. C. (2014). A Novel Function of Giant Ankyrin-G in Promoting the Formation of Somatodendritic GABAA Receptor Synaptogenesis . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/9407

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tseng, Wei Chou. “A Novel Function of Giant Ankyrin-G in Promoting the Formation of Somatodendritic GABAA Receptor Synaptogenesis .” 2014. Thesis, Duke University. Accessed January 20, 2021. http://hdl.handle.net/10161/9407.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tseng, Wei Chou. “A Novel Function of Giant Ankyrin-G in Promoting the Formation of Somatodendritic GABAA Receptor Synaptogenesis .” 2014. Web. 20 Jan 2021.

Vancouver:

Tseng WC. A Novel Function of Giant Ankyrin-G in Promoting the Formation of Somatodendritic GABAA Receptor Synaptogenesis . [Internet] [Thesis]. Duke University; 2014. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10161/9407.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tseng WC. A Novel Function of Giant Ankyrin-G in Promoting the Formation of Somatodendritic GABAA Receptor Synaptogenesis . [Thesis]. Duke University; 2014. Available from: http://hdl.handle.net/10161/9407

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

16. Tran, Phu. Mutational-kinetic Analysis Reveals the Roles of Arginines and Aromatics in the Core of the GABAA Receptor Ligand-binding Pocket.

Degree: 2011, Marquette University

URL: https://epublications.marquette.edu/dissertations_mu/112

► The γ-aminobutyric acid type A (GABA) receptor is a member of the cys-loop family of ligand-gated ion channels that plays a crucial role in normal… (more)

▼ The γ-aminobutyric acid type A (GABA) receptor is a member of the cys-loop family of ligand-gated ion channels that plays a crucial role in normal brain function by transducing the majority of inhibitory neurotransmission in the central nervous system. The studies documented in this dissertation were aimed at validating and refining the current best model for the interaction of GABA with the GABAA receptor via structure-function perturbation analysis. Mutational-kinetic data was used in conjunction with homology modeling knowledge to draw up architectural and functional roles of the arginines and aromatics in GABA-binding pocket. The results provide interesting new insights. Two positively charged arginine residues, which have been implicated in ligand binding, were profiled through serial mutagenesis, to get at the specific side chain properties required for the roles they serve. The structural and functional contribution of four aromatic residues were examined through measuring the influence of their side chain on GABA binding rate with respect to changes caused by point mutations. An interaction between two aromatic residues critical for proper ligand binding was discovered through a screen for functional coupling between them and four neighboring arginines. These results were subsequently employed in an attempt to refine the current ligand-receptor interaction model, proposing specific roles for the amino acid residues studied. In the current best model of the GABAA receptor's ligand-binding pocket, the amino moiety of GABA is coordinated by a cation-π interaction with β2Y97 and the carboxyl moiety coordinated by an interaction with either β2R207 or α1R67 (or possibly both). Here, we incorporate the results of this dissertation to modify and add significant detail to this model. The model proposed here includes the following features: a hydrophobic interaction between β2Y97 and β2F200, an inter-subunit cation-π interaction between β2Y97 and α1R132, a cation-π interaction between the amino group of GABA and β2F200, hydrogen bond(s) between the carboxyl end of GABA and the guanidinium group of α1R67, and an interaction between the side chain of β2R207 and the backbone carbonyl of β2Y97. Advisors/Committee Members: Wagner, David A., Buchanan, James, Fitts, Robert H..

Subjects/Keywords: GABA; Amino acid neurotransmitters – Receptors; Ligands; Biology – Dissertations binding; GABA; GABAA; modulation; pocket; receptor; Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tran, P. (2011). Mutational-kinetic Analysis Reveals the Roles of Arginines and Aromatics in the Core of the GABAA Receptor Ligand-binding Pocket. (Thesis). Marquette University. Retrieved from https://epublications.marquette.edu/dissertations_mu/112

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tran, Phu. “Mutational-kinetic Analysis Reveals the Roles of Arginines and Aromatics in the Core of the GABAA Receptor Ligand-binding Pocket.” 2011. Thesis, Marquette University. Accessed January 20, 2021. https://epublications.marquette.edu/dissertations_mu/112.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tran, Phu. “Mutational-kinetic Analysis Reveals the Roles of Arginines and Aromatics in the Core of the GABAA Receptor Ligand-binding Pocket.” 2011. Web. 20 Jan 2021.

Vancouver:

Tran P. Mutational-kinetic Analysis Reveals the Roles of Arginines and Aromatics in the Core of the GABAA Receptor Ligand-binding Pocket. [Internet] [Thesis]. Marquette University; 2011. [cited 2021 Jan 20]. Available from: https://epublications.marquette.edu/dissertations_mu/112.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tran P. Mutational-kinetic Analysis Reveals the Roles of Arginines and Aromatics in the Core of the GABAA Receptor Ligand-binding Pocket. [Thesis]. Marquette University; 2011. Available from: https://epublications.marquette.edu/dissertations_mu/112

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

17. Πετρίδης, Θεόδωρος. In vivo και in vitro μελέτες της φυσιολογίας και της φαρμακολογίας της GABA-εργικής συναπτικής αναστολής στον εγκέφαλο μυών και επίμυων.

Degree: 2008, University of Patras

URL: http://nemertes.lis.upatras.gr/jspui/handle/10889/778

►

Κύριος στόχος της εργασίας ήταν η συγκριτική μελέτη της παλίνδρομης αναστολής μεταξύ του ραχιαίου και του κοιλιακού πόλου του ιππόκαμπου αρουραίου. Χρησιμοποιήθηκε η μεθοδολογία της… (more)

▼

Κύριος στόχος της εργασίας ήταν η συγκριτική μελέτη της παλίνδρομης αναστολής μεταξύ του ραχιαίου και του κοιλιακού πόλου του ιππόκαμπου αρουραίου. Χρησιμοποιήθηκε η μεθοδολογία της in vitro διατήρησης τομών ιππόκαμπου και εξωκυττάριων καταγραφών προκλητών δυναμικών πεδίου. Τα αποτελέσματά μας έδειξαν ότι η GABAA εξαρτώμενη παλίνδρομη αναστολή είναι ασθενέστερη, έχει μικρότερη διάρκεια και φθίνει πιο γρήγορα στον κοιλιακό σε σχέση με το ραχιαίο ιππόκαμπο. Χρησιμοποιώντας διάφορα φάρμακα που δρουν ενισχυτικά στον GABAA υποδοχέα δείξαμε ότι υπάρχει λειτουργική διαφοροποίηση του GABAA εξαρτώμενου ανασταλτικού μηχανισμού μεταξύ των δύο πόλων του ιππόκαμπου, ενισχύοντας την υπόθεση της λειτουργικής διαφοροποίησης στο επίπεδο του υποδοχέα μεταξύ των δύο πόλων. Στην in vivo μελέτη, χρησιμοποιώντας το μοντέλο επαγωγής επιληπτικών κρίσεων με χορήγηση πεντυλενοτετραζόλης, δείξαμε ότι η ενίσχυση της GABAA εξαρτώμενης αναστολής απο τα κατασταλτικά φάρμακα συσχετίζεται με το μέγεθος της αντιεπιληπτικής τους δράσης. Επιπλέον, η βιταμίνη D δεν παρουσίασε αντιεπιληπτική δράση στους C57BL/6J μύες, ούτε ενίσχυσε την αναστολή, κάτι που δείχνει ότι δεν έχει επίδραση στον GABAA υποδοχέα ή, τουλάχιστον, στους υπότυπούς του στον ιππόκαμπο.

The major aim of this work was the comparative study of recurrent inhibition between the dorsal and ventral pole of the rat hippocampus. We used the methodology of in vitro maintenance of hippocampal slices and recording of evoked field potentials. We showed that the GABAA mediated recurrent inhibition is weaker, lasts less and decays faster in ventral than in dorsal hippocampus. Using various drugs that act as positive allosteric modulators of the GABAA receptor, we showed that there is a functional differentiation of the GABAA inhibitory mechanism between the two hippocampal poles, strengthening the hypothesis of the functional differentiation at the level of the receptor between the two poles. In the in vivo study, using the pentylenetetrazole model for inducing epileptic seizures, we showed that the enhancement of the GABAA mediated recurrent inhibition correlates with the strength of antiepileptic action of the sedative drugs used. In addition vitamin D did not show antiepileptic action in C57BL/6J mice. Moreover it didn’t enhance recurrent inhibition, showing that it doesn’t have any action on the GABAA receptor or, at least, on its subtypes in hippocampus.

Advisors/Committee Members: Γιομπρές, Παναγιώτης, Petrides, Theodoros, Γιομπρές, Παναγιώτης, Κωστόπουλος, Γεώργιος, Παπαθεοδωρόπουλος, Κωνσταντίνος, Μητσάκου, Αδαμαντία, Ματσώκης, Νικόλαος, Βαράκης, Ιωάννης, Φλωρδέλλης, Χριστόδουλος.

Subjects/Keywords: Ιππόκαμπος; Παλίνδρομη αναστολή; Τομή ιππόκαμπου; GABAA υποδοχέας; Κατασταλτικά φάρμακα; Πεντυλενοτετραζόλη; Επιληψία; Βιταμίνη D; 615.78; Hippocampus; Recurrent inhibition; Hippocampal slice; GABAA receptor; Sedative drugs; Pentylenetetrazole; Epilepsy; Vitamin D

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Πετρίδης, �. (2008). In vivo και in vitro μελέτες της φυσιολογίας και της φαρμακολογίας της GABA-εργικής συναπτικής αναστολής στον εγκέφαλο μυών και επίμυων. (Doctoral Dissertation). University of Patras. Retrieved from http://nemertes.lis.upatras.gr/jspui/handle/10889/778

Chicago Manual of Style (16^th Edition):

Πετρίδης, Θεόδωρος. “In vivo και in vitro μελέτες της φυσιολογίας και της φαρμακολογίας της GABA-εργικής συναπτικής αναστολής στον εγκέφαλο μυών και επίμυων.” 2008. Doctoral Dissertation, University of Patras. Accessed January 20, 2021. http://nemertes.lis.upatras.gr/jspui/handle/10889/778.

MLA Handbook (7^th Edition):

Πετρίδης, Θεόδωρος. “In vivo και in vitro μελέτες της φυσιολογίας και της φαρμακολογίας της GABA-εργικής συναπτικής αναστολής στον εγκέφαλο μυών και επίμυων.” 2008. Web. 20 Jan 2021.

Vancouver:

Πετρίδης �. In vivo και in vitro μελέτες της φυσιολογίας και της φαρμακολογίας της GABA-εργικής συναπτικής αναστολής στον εγκέφαλο μυών και επίμυων. [Internet] [Doctoral dissertation]. University of Patras; 2008. [cited 2021 Jan 20]. Available from: http://nemertes.lis.upatras.gr/jspui/handle/10889/778.

Council of Science Editors:

Πετρίδης �. In vivo και in vitro μελέτες της φυσιολογίας και της φαρμακολογίας της GABA-εργικής συναπτικής αναστολής στον εγκέφαλο μυών και επίμυων. [Doctoral Dissertation]. University of Patras; 2008. Available from: http://nemertes.lis.upatras.gr/jspui/handle/10889/778

18. Hsieh, Yee-Hsee. BRAINSTEM GABAA RECEPTOR SHAPE THE RESPONSE AND ADAPTATION TO HYPOXIA.

Degree: PhD, Pharmacology, 2007, Case Western Reserve University School of Graduate Studies

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1184267396

► Exposure to hypoxia, a decrease in oxygen levels, evokes a compensatory response. Acute hypoxia triggers a distinct pattern of respiratory and sympathetic motor activity during… (more)

▼ Exposure to hypoxia, a decrease in oxygen levels, evokes a compensatory response. Acute hypoxia triggers a distinct pattern of respiratory and sympathetic motor activity during and after hypoxia. The evoked motor response results from integration of peripheral and central chemo-sensitive afferent inputs by the sympatho-respiratory neural network in the brainstem. Although several neurotransmitter systems and neuronal populations are involved in mediating the hypoxic response, the circuitry is unclear. Previous studies demonstrated that release of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, depresses respiratory activity during hypoxia. In addition, neuronal populations in the pons, a portion of the brainstem, mediate a decrease in respiratory frequency during and after hypoxia. Thus, we hypothesized that GABA _Areceptors in the pons participate in the hypoxic response. To explore the role of the GABA _Areceptor in the acute hypoxic response, the receptor antagonist bicuculline was microinjected into regions involved in sympatho-respiratory neural control in the ventrolateral (vl) pons. This intervention altered only one component of the hypoxic response, the hypoxic ventilatory decline (HVD). Additional studies demonstrated that the acute hypoxic response was blunted by conditioning rats for 14 d to chronic hypobaric hypoxia (CHH), a model of living at high altitude. In addition, long-term facilitation (LTF), a persistent increase in the sympatho-respiratory activity after repeated hypoxic challenges, was attenuated. The expression of LTF is mediated in part by neuronal populations in the pons. Our results revealed that GABA _Areceptor subunit expression in the pons changes along with the CHH-induced physiologic changes. Upregulation of the GABA _Areceptor alpha 4 subunit mRNA expression occurred after 7 d CHH. Furthermore, de novo expression of delta and alpha 6, normally found exclusively in the cerebellum, was observed after 14 d. Binding assays confirmed the increase in receptors and immunohistochemistry verified that CHH-induced GABA _Areceptor subunit expression was localized in sympatho-respiratory areas within the pons. Together, our findings suggest that GABA _Areceptor expression in the pons participates in the physiologic response and adaptation of the sympatho-respiratory system to hypoxia. Advisors/Committee Members: Siegel, Ruth (Advisor).

Subjects/Keywords: Biology, Neuroscience; HYPOXIA; Hypoxic; sSNA; CHH; GABAA; GABAA RECEPTOR; Pons

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hsieh, Y. (2007). BRAINSTEM GABAA RECEPTOR SHAPE THE RESPONSE AND ADAPTATION TO HYPOXIA. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1184267396

Chicago Manual of Style (16^th Edition):

Hsieh, Yee-Hsee. “BRAINSTEM GABAA RECEPTOR SHAPE THE RESPONSE AND ADAPTATION TO HYPOXIA.” 2007. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed January 20, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1184267396.

MLA Handbook (7^th Edition):

Hsieh, Yee-Hsee. “BRAINSTEM GABAA RECEPTOR SHAPE THE RESPONSE AND ADAPTATION TO HYPOXIA.” 2007. Web. 20 Jan 2021.

Vancouver:

Hsieh Y. BRAINSTEM GABAA RECEPTOR SHAPE THE RESPONSE AND ADAPTATION TO HYPOXIA. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 2007. [cited 2021 Jan 20]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1184267396.

Council of Science Editors:

Hsieh Y. BRAINSTEM GABAA RECEPTOR SHAPE THE RESPONSE AND ADAPTATION TO HYPOXIA. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 2007. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1184267396

19. Furukawa, Tomonori. Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex : 胎生期マウス大脳皮質神経細胞の放射状移動におけるタウリン誘発性持続的GABAA受容体活性化の役割.

Degree: 博士（医学）, 2014, Hamamatsu University School of Medicine / 浜松医科大学

URL: http://hdl.handle.net/10271/2795

►

γ-Aminobutyricacid(GABA) depolarizes embryonic cerebrocortical neurons and continuous activation of the GABAA receptor (GABAAR) contributes to their tonic depolarization. Although multiple reports have demonstrated a role… (more)

▼

γ-Aminobutyricacid(GABA) depolarizes embryonic cerebrocortical neurons and continuous activation of the GABAA receptor (GABAAR) contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABAAR activation in neocortical development, including in migration, most of these studies have used pharmacological blockers. Herein, we performed in utero electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice (GAD67GFP/GFP) to label neurons born in the ventricular zone. Three days after electroporation, there were no differences in the distribution of labeled cells between the genotypes. The dose–response properties of labeled cells to GABA were equivalent among genotypes. However, continuous blockade of GABAAR with the GABAAR antagonist SR95531 accelerated radial migration. This effect of GABAR blockade in GAD67GFP/GFPA mice suggested a role for alternative endogenous GABAAR agonists. Thus, we tested the role of taurine, which is derived from maternal blood but is abundant in the fetal brain. The taurine-evoked currents in labeled cells were mediated by GABAAR. Taurine uptake was blocked by a taurine transporter inhibitor, 2-(guanidino)ethanesulfonic acid (GES), and taurine release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7-dichlor-2-cyclopentylindan-1-on-5-yl) oxobutyric acid, as examined through high-performance liquid chromatography. GES increased the extracellular taurine concentration and induced an inward shift of the holding current, which was reversed by SR95531. In a taurine-deficient mouse model, the GABAAR-mediated tonic currents were greatly reduced, and radial migration was accelerated. As the tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice, taurine, rather than GABA, might play a major role as an endogenous agonist of embryonic tonic GABAAR conductance, regulating the radial migration of neurons in the developing neocortex.

浜松医科大学学位論文　医博論第513号（平成26年6月20日）

Subjects/Keywords: taurine; GABAA receptor; tonic current; radial migration; non-vesicular release; volume-sensitive anion channel; GAD67; taurine transporter

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Furukawa, T. (2014). Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex : 胎生期マウス大脳皮質神経細胞の放射状移動におけるタウリン誘発性持続的GABAA受容体活性化の役割. (Thesis). Hamamatsu University School of Medicine / 浜松医科大学. Retrieved from http://hdl.handle.net/10271/2795

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Furukawa, Tomonori. “Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex : 胎生期マウス大脳皮質神経細胞の放射状移動におけるタウリン誘発性持続的GABAA受容体活性化の役割.” 2014. Thesis, Hamamatsu University School of Medicine / 浜松医科大学. Accessed January 20, 2021. http://hdl.handle.net/10271/2795.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Furukawa, Tomonori. “Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex : 胎生期マウス大脳皮質神経細胞の放射状移動におけるタウリン誘発性持続的GABAA受容体活性化の役割.” 2014. Web. 20 Jan 2021.

Vancouver:

Furukawa T. Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex : 胎生期マウス大脳皮質神経細胞の放射状移動におけるタウリン誘発性持続的GABAA受容体活性化の役割. [Internet] [Thesis]. Hamamatsu University School of Medicine / 浜松医科大学; 2014. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10271/2795.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Furukawa T. Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex : 胎生期マウス大脳皮質神経細胞の放射状移動におけるタウリン誘発性持続的GABAA受容体活性化の役割. [Thesis]. Hamamatsu University School of Medicine / 浜松医科大学; 2014. Available from: http://hdl.handle.net/10271/2795

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Michigan

20. Bianchi, Matt T. GABA(A) receptor properties that shape neuronal inhibition.

Degree: PhD, Neurosciences, 2004, University of Michigan

URL: http://hdl.handle.net/2027.42/124020

► GABA_A receptors are chloride selective ligand-gated ion channels that mediate inhibitory neuronal signaling in the adult central nervous system. Native receptors are pentameric combinations of… (more)

▼ GABA_A receptors are chloride selective ligand-gated ion channels that mediate inhibitory neuronal signaling in the adult central nervous system. Native receptors are pentameric combinations of various subunits with expression patterns that are highly regulated with respect to anatomical location as well as developmental period. Although the physiological significance of such molecular diversity remains poorly understood, the striking subunit-dependence of kinetic properties and pharmacological modulation may provide a broad range of inhibition 'strategies' to the brain. The primary aim of this thesis was to determine the relevance of various GABA_A receptor properties for synaptic (non-equilibrium) and extra-synaptic (steady-state) forms of neuronal inhibition. A fibroblast expression system allowed molecular manipulations (mutations, chimeras) of receptor subunits, as well as precise kinetic measurements (concentration jump technique) of GABA_A receptor function to be achieved. This combined approach revealed several important receptor properties that may regulate the time course, efficacy, and pharmacological modulation of GABA_A receptor-mediated inhibition. Specifically, we developed a novel functional assay to demonstrate a fundamental constraint on the relationship between GABA binding and channel gating: all kinetic states from which channel opening occurs are agonist-bound; GABA unbinding is unlikely or not possible from open and desensitized states. This finding provided a conceptual framework for subsequent hypothesis testing of the specific impact of gating efficacy, desensitization and microscopic affinity on GABA_A deactivation, the major determinant of inhibitory post-synaptic current (IPSC) duration. Experimental data, supported by computer simulation results, indicated independent contributions of these three receptor properties to GABA_A receptor deactivation. These insights laid the foundation for functional evaluation of the first GABA_A receptor mutations linked to human epilepsy and sleep syndromes. Additional work on the properties and regulation of putative extra-synaptic GABA_A receptor isoforms, that are thought to mediate tonic inhibition, revealed clear subunit-dependent biophysical and pharmacological properties. Analysis of modulation by an endogenous neurosteroid indicated that these isoforms are subject to a surprisingly dynamic range of regulation. Moreover, detailed functional analysis led us to propose a novel mechanism for isoform-specific allosteric modulation that distinguishes GABA_A receptors based on differences in gating efficacy rather than primary protein structure. Advisors/Committee Members: Macdonald, Robert L. (advisor), Hume, Richard (advisor).

Subjects/Keywords: Desensitization; Gaba; Gabaa Receptor; Neuronal Inhibition; Neurosteroid; Properties; Shape

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bianchi, M. T. (2004). GABA(A) receptor properties that shape neuronal inhibition. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/124020

Chicago Manual of Style (16^th Edition):

Bianchi, Matt T. “GABA(A) receptor properties that shape neuronal inhibition.” 2004. Doctoral Dissertation, University of Michigan. Accessed January 20, 2021. http://hdl.handle.net/2027.42/124020.

MLA Handbook (7^th Edition):

Bianchi, Matt T. “GABA(A) receptor properties that shape neuronal inhibition.” 2004. Web. 20 Jan 2021.

Vancouver:

Bianchi MT. GABA(A) receptor properties that shape neuronal inhibition. [Internet] [Doctoral dissertation]. University of Michigan; 2004. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/2027.42/124020.

Council of Science Editors:

Bianchi MT. GABA(A) receptor properties that shape neuronal inhibition. [Doctoral Dissertation]. University of Michigan; 2004. Available from: http://hdl.handle.net/2027.42/124020

Penn State University

21. Murakami, Shoko. ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8917

► Type A GABA receptors (GABAARs) are the major sites of fast synaptic inhibition in the central nervous system (CNS) and mediate the therapeutic effects of… (more)

▼ Type A GABA receptors (GABAARs) are the major sites of fast synaptic inhibition in the central nervous system (CNS) and mediate the therapeutic effects of many clinically important drugs. The efficacy of synaptic inhibition is critically dependent on the postsynaptic accumulation of GABAARs. Golgi-specific DHHC zinc finger protein (GODZ; aka, DHHC3) and SERZ-beta (aka, DHHC7) have been identified as palmitoyl acyl-transferases (PATs) of the gamma2 subunit of GABAARs. In addition, the cell adhesion molecule neuroligin 2 (NL2) is localized at GABAergic synapses and implicated in GABAergic synapse formation. Previous analyses of GODZ by RNAi in cultured neurons had suggested that they are important for postsynaptic accumulation of GABAARs at inhibitory synapses. In addition these studies pointed to a novel possible role of GABAARs in the assembly of GABAergic inhibitory synapses. A first objective of this doctoral thesis was to elucidate the function of GODZ and SERZ-beta in vivo. In order to achieve this purpose, global and conditional knock-out (KO) mice were generated for both GODZ and SERZ-beta. Genetic deletion of GODZ and SERZ-beta was confirmed by genomic Southern blotting, RT-PCR and immunofluorescence analyses. Global GODZ and SERZ-beta KO mice were found to be viable, whereas GODZ and SERZ-beta double knock-out (DKO) mice showed a partially penetrant perinatally lethal phenotype. Male, but not female, GODZ KO mice exhibited a small but significant reduction in body weight compared to wild type (WT) littermate controls. A more dramatic reduction in body weight was evident in DKO mice, as quantified in females but also overtly evident in males. Compared to WT littermate controls, GODZ KO mice showed complex behavioral alterations characterized by excessive jumping in response to handling, hindleg clenching upon suspension by their tail, hyperlocomotion in an Open Field test, as well as enhanced Prepulse Inhibition of acoustic startle responses. However, GODZ KOs showed normal anxiety related behavior in Free Choice and Elevated Plus Maze tests. Immunofluorescence analyses of cortical neuron cultures prepared from GODZ KO or GODZ/SERZ-beta DKO mice revealed unaltered numbers of postsynaptic clusters of gamma2 subunit containing GABAARs and the inhibitory postsynaptic scaffold protein gephyrin. Similarly, the number of clusters of the corresponding presynaptic marker glutamate decarboxylase (GAD) and vesicular inhibitory amino acid transporter (VIATT) were also unchanged. Consistent with unaltered clustering in pure DKO cultures, the surface expression levels of the gamma2 subunit and NL2 assessed by biotinylation was unaltered in DKO compared to WT cultures. However, when mutant neurons were co-cultured with an excess of WT neurons, punctate staining for postsynaptic GABAAR clusters and presynaptic inhibitory synaptic markers of GODZ KO and DKO neurons was dramatically reduced compared to neurons of pure WT cultures. Similarly, gamma2 subunit heterozygous neurons co-cultured with an excess of WT neurons showed a… Advisors/Committee Members: Bernhard Luscher, Dissertation Advisor/Co-Advisor, Bernhard Luscher, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Robert Paulson, Committee Member, Gong Chen, Committee Member, Erin Elizabeth Sheets, Committee Member.

Subjects/Keywords: knock out; trafficking; Neuroligin 2; GABAA receptor; palmitoylation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Murakami, S. (2008). ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8917

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Murakami, Shoko. “ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE .” 2008. Thesis, Penn State University. Accessed January 20, 2021. https://submit-etda.libraries.psu.edu/catalog/8917.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Murakami, Shoko. “ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE .” 2008. Web. 20 Jan 2021.

Vancouver:

Murakami S. ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Jan 20]. Available from: https://submit-etda.libraries.psu.edu/catalog/8917.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Murakami S. ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8917

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Edinburgh

22. O'Neill, Nathanael. Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells.

Degree: PhD, 2020, University of Edinburgh

URL: http://hdl.handle.net/1842/37176

► GABAA receptors (GABAARs) are the principal inhibitory neurotransmitter receptors in the adult mammalian central nervous system. GABAARs mediate two forms of inhibition: fast, phasic conductance;… (more)

▼ GABAA receptors (GABAARs) are the principal inhibitory neurotransmitter receptors in the adult mammalian central nervous system. GABAARs mediate two forms of inhibition: fast, phasic conductance; and slow, tonic conductance. Tonic conductance arises due to the persistent activation of GABAARs. This persistent activation can occur by GABA-dependent or GABAindependent mechanisms. Low concentrations of ambient GABA activate high affinity GABAARs located outside the synapse – at peri-/extra-synaptic sites – to generate GABA-dependent tonic conductance. In contrast, GABA-independent tonic conductance is generated by GABAARs that activate spontaneously, in the absence of GABA, due to constitutive receptor gating. Because spontaneously active GABAARs (s-GABAARs) do not require GABA to activate, they are resistant competitive antagonists, e.g. SR-95531, but can be inhibited by the channel-blockers, e.g. picrotoxin. s-GABAARs have been shown to produce GABA-independent tonic conductances in the hippocampus and the amygdala. However, despite the good evidence for the presence of sGABAARs, their function and pharmacology remain largely unknown. Here we show, for the first time, using both current- and voltage-clamp recording techniques, that the s-GABAAR-mediated tonic conductance exerts a powerful inhibitory effect in rat dentate gyrus granule cells. We find that at resting membrane potential, s-GABAARs generate a shunting conductance that decreases both the membrane resistance and the membrane time constant of the neuron. When the membrane potential is depolarised, s-GABAARs conduct hyperpolarising currents that exhibit outward-rectification; this means that their net inhibitory effect is greater when the neuron is close to firing threshold than when it is at rest. Consistent with this, we find that block of s-GABAARs shifts the neuron into a more excitable state, as evidenced by the increase in the gain of the input-output relationship and the decrease in the rheobase current and the hyperpolarisation of the action potential threshold. At the network level, s-GABAARs regulate the precision of signal transmission in the dentate gyrus: blocking sGABAARs widens the temporal window over which multiple excitatory inputs can be successfully summated to generate an action potential. Finally, we report that s-GABAAR tonic currents are resistant to pharmacological compounds that target extrasynaptic GABAARs (L-655,708 and DS2), but are augmented by the clinically used benzodiazepine site modulators, zolpidem and midazolam, and partially inhibited by the inverse agonist, DMCM. The sensitivity of s-GABAARs to these compounds suggests the involvement of the γ2-subunit.

Subjects/Keywords: GABAergic; GABAA Receptor; GABA; Interneuron; hippocampus; electrophysiology; patch-clamp; LTP; benzodiazepine; spontaneous activity; constitutive activity; epilepsy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

O'Neill, N. (2020). Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/37176

Chicago Manual of Style (16^th Edition):

O'Neill, Nathanael. “Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells.” 2020. Doctoral Dissertation, University of Edinburgh. Accessed January 20, 2021. http://hdl.handle.net/1842/37176.

MLA Handbook (7^th Edition):

O'Neill, Nathanael. “Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells.” 2020. Web. 20 Jan 2021.

Vancouver:

O'Neill N. Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells. [Internet] [Doctoral dissertation]. University of Edinburgh; 2020. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1842/37176.

Council of Science Editors:

O'Neill N. Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells. [Doctoral Dissertation]. University of Edinburgh; 2020. Available from: http://hdl.handle.net/1842/37176

University of Edinburgh

23. O'Neill, Nathanael. Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells.

Degree: PhD, 2020, University of Edinburgh

URL: https://doi.org/10.7488/era/477 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.810231

► GABAA receptors (GABAARs) are the principal inhibitory neurotransmitter receptors in the adult mammalian central nervous system. GABAARs mediate two forms of inhibition: fast, phasic conductance;… (more)

▼ GABAA receptors (GABAARs) are the principal inhibitory neurotransmitter receptors in the adult mammalian central nervous system. GABAARs mediate two forms of inhibition: fast, phasic conductance; and slow, tonic conductance. Tonic conductance arises due to the persistent activation of GABAARs. This persistent activation can occur by GABA-dependent or GABAindependent mechanisms. Low concentrations of ambient GABA activate high affinity GABAARs located outside the synapse – at peri-/extra-synaptic sites – to generate GABA-dependent tonic conductance. In contrast, GABA-independent tonic conductance is generated by GABAARs that activate spontaneously, in the absence of GABA, due to constitutive receptor gating. Because spontaneously active GABAARs (s-GABAARs) do not require GABA to activate, they are resistant competitive antagonists, e.g. SR-95531, but can be inhibited by the channel-blockers, e.g. picrotoxin. s-GABAARs have been shown to produce GABA-independent tonic conductances in the hippocampus and the amygdala. However, despite the good evidence for the presence of sGABAARs, their function and pharmacology remain largely unknown. Here we show, for the first time, using both current- and voltage-clamp recording techniques, that the s-GABAAR-mediated tonic conductance exerts a powerful inhibitory effect in rat dentate gyrus granule cells. We find that at resting membrane potential, s-GABAARs generate a shunting conductance that decreases both the membrane resistance and the membrane time constant of the neuron. When the membrane potential is depolarised, s-GABAARs conduct hyperpolarising currents that exhibit outward-rectification; this means that their net inhibitory effect is greater when the neuron is close to firing threshold than when it is at rest. Consistent with this, we find that block of s-GABAARs shifts the neuron into a more excitable state, as evidenced by the increase in the gain of the input-output relationship and the decrease in the rheobase current and the hyperpolarisation of the action potential threshold. At the network level, s-GABAARs regulate the precision of signal transmission in the dentate gyrus: blocking sGABAARs widens the temporal window over which multiple excitatory inputs can be successfully summated to generate an action potential. Finally, we report that s-GABAAR tonic currents are resistant to pharmacological compounds that target extrasynaptic GABAARs (L-655,708 and DS2), but are augmented by the clinically used benzodiazepine site modulators, zolpidem and midazolam, and partially inhibited by the inverse agonist, DMCM. The sensitivity of s-GABAARs to these compounds suggests the involvement of the γ2-subunit.

Subjects/Keywords: GABAergic; GABAA Receptor; GABA; Interneuron; hippocampus; electrophysiology; patch-clamp; LTP; benzodiazepine; spontaneous activity; constitutive activity; epilepsy

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

O'Neill, N. (2020). Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells. (Doctoral Dissertation). University of Edinburgh. Retrieved from https://doi.org/10.7488/era/477 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.810231

Chicago Manual of Style (16^th Edition):

O'Neill, Nathanael. “Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells.” 2020. Doctoral Dissertation, University of Edinburgh. Accessed January 20, 2021. https://doi.org/10.7488/era/477 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.810231.

MLA Handbook (7^th Edition):

O'Neill, Nathanael. “Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells.” 2020. Web. 20 Jan 2021.

Vancouver:

O'Neill N. Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells. [Internet] [Doctoral dissertation]. University of Edinburgh; 2020. [cited 2021 Jan 20]. Available from: https://doi.org/10.7488/era/477 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.810231.

Council of Science Editors:

O'Neill N. Functional characterisation of spontaneously active GABAA receptors in rat dentate gyrus granule cells. [Doctoral Dissertation]. University of Edinburgh; 2020. Available from: https://doi.org/10.7488/era/477 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.810231

University of Sydney

24. Skilbeck, Kelly Johanne. Stress and GABAA receptor regulation .

Degree: 2008, University of Sydney

URL: http://hdl.handle.net/2123/4997

► GABAA receptors are implicated in the pathology of psychiatric disorders such as schizophrenia and depression. They are rapidly affected by stress in a sex-dependent fashion,… (more)

▼ GABAA receptors are implicated in the pathology of psychiatric disorders such as schizophrenia and depression. They are rapidly affected by stress in a sex-dependent fashion, suggesting that GABAA receptors may be relevant to understanding the association between stress and psychiatric disorders. Thus, this thesis examined how GABAA receptors are affected in both male and female mice exposed to stress in adulthood (Chapter 2), early-life (Chapter 3-5) and a combination of both early-life and adulthood stress (Chapter 6). 2. The effects of acute adulthood stress (3 minute warm swim stress) on GABAA receptor binding in the brains of male and female mice were examined using quantitative receptor autoradiography. The total number of GABAA receptor [3H]GABA binding sites was increased following swim stress in specific forebrain cortical regions of female mice swum individually or in a group, but decreased in male mice when swum in a group only. These findings confirm and extend previous studies, identifying the cortical regions involved in rapid stress-induced changes in GABAA receptors. 3. Post-natal handling models in rodents comparing control (brief handling sessions; EH) with no intervention stress conditions (NH), indicate that the NH condition results in an anxious adulthood phenotype and this was confirmed in the present thesis using the elevated plus-maze behavioural test. Using this model the effects of early-life stress on adulthood GABAA receptors were then examined. 4. Regional densities of GABAA receptor α1 and α2 subunit proteins were observed in the adult brain of male and female mice using immunoperoxidase histochemistry. NH males showed a loss of the α2 subunit from the thalamus and the lower layers (IV-VI) of the primary somatosensory cortex, whilst NH females showed a reduction of α2 but an increase in α1 protein in the lower layers of the primary somatosensory cortex only. These regionally specific alterations in the α1:α2 subunit ratio suggest that early-life stress disrupts the developmental α subunit switch, which occurs in a regionally-dependent fashion over the first two weeks of rodent life. 5. Double-labelling immunofluorescence and confocal microscopy were used to examine the effects of sex and early-life stress on GABAA receptor synaptic clustering. Regardless of sex, mice exposed to early-life stress (NH) showed reduced colocalisation of the GABAA receptor α2 subunit with the synaptic marker protein gephyrin relative to the control condition (EH). This suggests that early-life stress impairs adulthood inhibitory synaptic strength and is consistent with the increased anxiety of the stressed relative to control mice. 6. Finally, the effects of early-life stress on adulthood swim stress-induced changes in GABAA receptor binding were examined using quantitative receptor autoradiography in forebrain cortical regions. Findings showed that the effect of adulthood stress on the total number of GABAA receptor binding sites for [3H]GABA in forebrain cortical regions was altered by…

Subjects/Keywords: GABAA receptor; Stress; sex differences; immunohistochemistry, immunofluorescence; quantitative receptor autoradiography

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Skilbeck, K. J. (2008). Stress and GABAA receptor regulation . (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/4997

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Skilbeck, Kelly Johanne. “Stress and GABAA receptor regulation .” 2008. Thesis, University of Sydney. Accessed January 20, 2021. http://hdl.handle.net/2123/4997.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Skilbeck, Kelly Johanne. “Stress and GABAA receptor regulation .” 2008. Web. 20 Jan 2021.

Vancouver:

Skilbeck KJ. Stress and GABAA receptor regulation . [Internet] [Thesis]. University of Sydney; 2008. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/2123/4997.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Skilbeck KJ. Stress and GABAA receptor regulation . [Thesis]. University of Sydney; 2008. Available from: http://hdl.handle.net/2123/4997

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Université de Montréal

25. Lachance-Touchette, Pamela. Criblage génétique et caractérisation fonctionnelle des mutations dans les différentes sous-unités du récepteur GABAA associées à l'épilepsie génétique généralisée.

Degree: 2015, Université de Montréal

URL: http://hdl.handle.net/1866/11834

Subjects/Keywords: Épilepsie génétique généralisée; Récepteur GABAA; Génétique; Genetic generalized epilepsy; GABAA receptor; Genetics; Biology - Genetics / Biologie - Génétique (UMI : 0369)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lachance-Touchette, P. (2015). Criblage génétique et caractérisation fonctionnelle des mutations dans les différentes sous-unités du récepteur GABAA associées à l'épilepsie génétique généralisée. (Thesis). Université de Montréal. Retrieved from http://hdl.handle.net/1866/11834

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lachance-Touchette, Pamela. “Criblage génétique et caractérisation fonctionnelle des mutations dans les différentes sous-unités du récepteur GABAA associées à l'épilepsie génétique généralisée.” 2015. Thesis, Université de Montréal. Accessed January 20, 2021. http://hdl.handle.net/1866/11834.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lachance-Touchette, Pamela. “Criblage génétique et caractérisation fonctionnelle des mutations dans les différentes sous-unités du récepteur GABAA associées à l'épilepsie génétique généralisée.” 2015. Web. 20 Jan 2021.

Vancouver:

Lachance-Touchette P. Criblage génétique et caractérisation fonctionnelle des mutations dans les différentes sous-unités du récepteur GABAA associées à l'épilepsie génétique généralisée. [Internet] [Thesis]. Université de Montréal; 2015. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1866/11834.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lachance-Touchette P. Criblage génétique et caractérisation fonctionnelle des mutations dans les différentes sous-unités du récepteur GABAA associées à l'épilepsie génétique généralisée. [Thesis]. Université de Montréal; 2015. Available from: http://hdl.handle.net/1866/11834

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Vienna

26. Hufnagel, Martina. Einfluss des β-Subtyps auf die Modulation von GABAA-Rezeptoren durch ausgewählte Liganden.

Degree: 2017, University of Vienna

URL: http://othes.univie.ac.at/48963/

►

Hintergrund: GABAA-Rezeptoren zählen zu den wichtigsten neuroinhibitorischen Rezeptoren im Gehirn. GABAA-Rezeptor-Modulatoren werden aufgrund ihrer anxiolytischen, sedierenden, antikonvulsiven und muskelrelaxierenden Wirkungen zur Therapie zahlreicher Erkrankungen eingesetzt.… (more)

▼

Hintergrund: GABAA-Rezeptoren zählen zu den wichtigsten neuroinhibitorischen Rezeptoren im Gehirn. GABAA-Rezeptor-Modulatoren werden aufgrund ihrer anxiolytischen, sedierenden, antikonvulsiven und muskelrelaxierenden Wirkungen zur Therapie zahlreicher Erkrankungen eingesetzt. Diese Substanzen sind wirksame Therapeutika, aber aufgrund ihrer meist unselektiven Interaktion mit zahlreichen GABAA-Rezeptor-Subtypen oft mit einer Reihe von Nebenwirkungen verbunden. Die Identifikation subtyp-selektiver Liganden steht daher im Vordergrund, um Substanzen mit spezifischerem Wirkprofil und einer reduzierten Anzahl unerwünschter Begleitwirkungen zu entwickeln. Zielsetzung: Im Rahmen dieser Diplomarbeit wurde die β-subtypspezifische Modulation von GABA-induzierten Chlorid-Strömen (IGABA) durch fünf Derivate (MH340, MH346, MH350, MH409, MH 661) des Naturstoffes Valerensäure (VA) an α1β1γ2S, α1β2γ2S und α1β3γ2S GABAA-Rezeptoren untersucht. Methode: Expression von α1β1γ2S, α1β2γ2S und α1β3γ2S GABAA-Rezeptoren in Xenopus laevis Oozyten und Messung der konzentrationsabhängigen Modulation von IGABA durch die Derivate mittels der 2-Mikroelektroden-Spannungsklemmtechnik. Ergebnisse und Diskussion: Die höchste Potenzierung von IGABA erreichte Derivat MH409 an α1β1γ2S Rezeptoren (Emax= 2206,7 ± 217,0%, n=5). Auch an β2/3-haltigen Rezeptoren wurde die GABAEC5-7 durch MH409 signifikant stärker potenziert als durch VA (Emax an β2: 1439,9 ± 101,0%, n=4; β3: 1118,3 ± 44,4%, n=3). MH409 ist damit das erste Valerensäure-Derivat, das eine wirksame und potente Modulation von β1-Rezeptoren aufweist. Derivat MH661 potenzierte IGABA ebenso an allen Rezeptorsubtypen signifikant stärker als VA (Emax an β1:417,5 ± 36,4%, n=3; β2: 1227,8 ± 140,4%, n=7; β3: 1260,6 ± 165,6%, n=6), die β2/3-Selektivität des Ausgangsstoffes blieb jedoch erhalten. Derivat MH340 potenzierte IGABA, verglichen mit VA, ähnlich stark (Emax an β1: 141,6 ± 52,2%, n=8; β2: 629,6 ± 124,0%, n=6; β3: 503,2 ± 68,0%, n=7), wies allerdings eine geringere Potenz auf. Die Derivate MH346 und MH350 modulierten α1β2/3γ2S Rezeptoren nur marginal und α1β1γ2S nicht signifikant. Diese Arbeit zeigt, dass Modifikation am Molekül der Valerensäure die Wirksamkeit, Potenz und die β-Subtyp-Selektivität drastisch beeinflussen. Ob und wie sich diese Modifikationen auf die Interaktion dieser Liganden mit deren Bindungsstellen am GABAA-Rezeptor sowie deren Wirkungen in vivo auswirken, sollte Fokus weiterer Untersuchungen sein.

Background: GABAA receptors represent the most important inhibitory neurotransmitter receptors in the brain. GABAA receptor modulators display anxiolytic, sedative, anticonvulsive and muscle relaxant effects and are therefore used to treat several disease states. These compounds are effective therapeutics, but are associated with several side effects due to their unselective modulation of several GABAA receptor subtypes. Therefore, the identification of subtype-selective ligands is crucial to develop compounds offering a more specific pharmacological profile and less side…

Subjects/Keywords: 30.30 Naturwissenschaften in Beziehung zu anderen Fachgebieten; 30.99 Naturwissenschaften allgemein: Sonstiges; 30.03 Methoden und Techniken in den Naturwissenschaften; GABA / GABAA-Rezeptor / Valerensäure / beta-Untereinheit / Xenopus laevis; GABA / GABAA-receptor / valerenic acid / beta-subunit / Xenopus laevis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hufnagel, M. (2017). Einfluss des β-Subtyps auf die Modulation von GABAA-Rezeptoren durch ausgewählte Liganden. (Thesis). University of Vienna. Retrieved from http://othes.univie.ac.at/48963/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hufnagel, Martina. “Einfluss des β-Subtyps auf die Modulation von GABAA-Rezeptoren durch ausgewählte Liganden.” 2017. Thesis, University of Vienna. Accessed January 20, 2021. http://othes.univie.ac.at/48963/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hufnagel, Martina. “Einfluss des β-Subtyps auf die Modulation von GABAA-Rezeptoren durch ausgewählte Liganden.” 2017. Web. 20 Jan 2021.

Vancouver:

Hufnagel M. Einfluss des β-Subtyps auf die Modulation von GABAA-Rezeptoren durch ausgewählte Liganden. [Internet] [Thesis]. University of Vienna; 2017. [cited 2021 Jan 20]. Available from: http://othes.univie.ac.at/48963/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hufnagel M. Einfluss des β-Subtyps auf die Modulation von GABAA-Rezeptoren durch ausgewählte Liganden. [Thesis]. University of Vienna; 2017. Available from: http://othes.univie.ac.at/48963/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

The Ohio State University

27. Chen, Zhixiong. Brainstem Mechanisms Underlying Ingestion and Rejection.

Degree: PhD, Dentistry, 2003, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1041523002

► Feeding behavior is controlled by brain structures distributed in the cerebral cortex, limbic system and brainstem. In the brainstem, a central pattern generator (CPG) for… (more)

▼ Feeding behavior is controlled by brain structures distributed in the cerebral cortex, limbic system and brainstem. In the brainstem, a central pattern generator (CPG) for mastication has been localized to the midline medullary reticular formation based on cortically induced rhythmic jaw movements (fictive mastication), or to the reticular formation (RF) between the trigeminal and facial motor nuclei based on chemically elicited rhythmic trigeminal discharge in a tissue slice preparation. Other studies, however, suggest a role for the lateral medullary RF in orchestrating ingestive oromotor activity. Direct behavioral evidence supporting the location of these CPGs, however, is lacking. Thus, the first study tested the hypothesis that the lateral medullary RF is essential for organizing oromotor patterns of ingestion and rejection. In the behaving rat, licking was induced by either intra-oral (IO) infusions of sucrose or saline, or sucrose presented in a bottle. Gaping (rejection) responses were elicited by IO delivery of quinine hydrochloride. All responses were measured electromyographically from the anterior digastric (jaw-opener) and geniohyoid (tongue-protruder) muscles. Inactivation of the lateral medullary RF with the GABAA agonist muscimol suppressed both licking and gaping. Infusions into other RF regions were ineffective, indicating an essential role for the lateral medullary RF. Because both excitatory and inhibitory amino acids (EAA, IAA) are involved in fictive mastication, we further examined whether they are also important for ingestive responses elicited by natural stimuli. In a second series of experiments, EAA and IAA antagonists were infused into the lateral medullary RF. It was found that (1) the lateral medullary RF is driven by glutamatergic inputs, mediated by both non-NMDA and NMDA receptors, (2) it is under tonic inhibition from GABAergic and glycinergic inputs, (3) this substrate is also involved in the suppression of eupnea that is mediated by non-NMDA receptors. These findings provide behavioral evidence to support the hypothesis that the lateral medullary RF is a multifunctional substrate that controls the oromotor nuclei to generate licking and gaping, and the oromotor components of gasping. Advisors/Committee Members: Travers, Joseph (Advisor).

Subjects/Keywords: Central pattern generator; NMDA receptor; Non-NMDA receptor; GABAA receptor; Glycine receptor; Taste oromotor processing

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chen, Z. (2003). Brainstem Mechanisms Underlying Ingestion and Rejection. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1041523002

Chicago Manual of Style (16^th Edition):

Chen, Zhixiong. “Brainstem Mechanisms Underlying Ingestion and Rejection.” 2003. Doctoral Dissertation, The Ohio State University. Accessed January 20, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1041523002.

MLA Handbook (7^th Edition):

Chen, Zhixiong. “Brainstem Mechanisms Underlying Ingestion and Rejection.” 2003. Web. 20 Jan 2021.

Vancouver:

Chen Z. Brainstem Mechanisms Underlying Ingestion and Rejection. [Internet] [Doctoral dissertation]. The Ohio State University; 2003. [cited 2021 Jan 20]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1041523002.

Council of Science Editors:

Chen Z. Brainstem Mechanisms Underlying Ingestion and Rejection. [Doctoral Dissertation]. The Ohio State University; 2003. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1041523002

28. Marcos Brandao Contó. Pharmacologycal and auto-radiographical study of GABAA/benzodiazepine site, and biochemical assays of the Na+/K+-ATPase and of the glutamatergic receptors in rats susceptible and non-susceptible to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist.

Degree: 2008, Universidade Federal de São Paulo

URL: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2609 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2610

►

Objective: The aim of this work was to verify if rats susceptible and non-susceptible to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist, differ:… (more)

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Objective: The aim of this work was to verify if rats susceptible and non-susceptible to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist, differ: 1) in the sensitivity to the hypnotic effect induced by diazepam and by others positive allosteric modulators of GABAA receptors; 2) in auto-radiographical analysis of [3H]-flunitrazepam binding along the brain; 3) in the binding of [3H]-L-glutamate and of [3H]-MK 801 in membranes from discrete brain regions; and 4) in the Na+/K+-ATPase activity, as well as in the binding of [3H]-ouabain to Na+/K+-ATPase isoenzimes with high and low affinity to the radioligand in membranes from discrete brain regions. Methods: Adult, male, Wistar rats were administered with two intraperitoneal injections of a convulsant dose 50% (CD50) of DMCM (one-week interval between them), resulting in two distinct groups: the group susceptible to clonic convulsions (SC), which presented clonic convulsions in both the expositions to the drug, and the group nonsusceptible to clonic convulsions (NSC), which did not present any motor disturbance in both the expositions. After 25 days from the second exposition to DMCM, the selected groups were submitted to the experiments with the hypnotics diazepam, pentobarbital and ethanol, in which were registered the latency and the time of sleep or they were sacrified and their brains were removed to carry out the following assays: 1) autoradiography with [3H]-flunitrazepam; 2) binding with the [3H]-L-glutamate and with the [3H]-MK 801 in neuronal membranes; 3) enzymatic activity of Na+/K+-ATPase and binding of [3H]-ouabain to the isoenzimes with high and low affinity in neuronal membranes. Results: The SC group presented a lower sleeping time induced by diazepam compared to the NSC group, and did not differ in the sleeping time induced by pentobarbital and ethanol. Concearning the biochemical experiments, it was observed a lower binding of [3H]-flunitrazepam in the CA2 subregion of ventral hippocampus in the SC group. A lower binding of [3H]-L-glutamate was also observed in the SC group in the frontal cortex, amygdala plus limbic cortex and hippocampus, whereas the binding of [3H]-MK 801 was lower in the frontal cortex, hippocampus and striatum compared to the NSC group. Althougt the groups did not differ in the enzymatic activity of Na+/K+- ATPase, the SC group presented a lower binding of [3H]-ouabain to the high-affinity isoenzimes in the brainstem, frontal cortex and hippocampus, as well as a lower binding of [3H]-ouabain to the low-affinity isoenzimes in the brainstem and in the frontal cortex compared to the NSC group. Conclusion: The differences between the groups concerning the sensitivity to the convulsant effect of DMCM, the level of anxiety previously observed, as well as the sensitivity to the hypnotic effect of diazepam may be associated with the GABAA/benzodiazepine site in CA2 subregion of ventral hippocampus, with glutamatergic activity and with specific isoforms of Na+/K+-ATPase in rat brain regions.

Objetivo: Verificar se…

Advisors/Committee Members: Jose Roberto Leite, Débora Cristina Hipólide, Helena Maria Tannhauser Barros, Reinaldo Naoto Takahashi, Marco Antonio Campana Benedito.

Subjects/Keywords: Convulsão clônica; Moduladores alostéricos do receptor GABAA; Auto-radiografia [3H]-Flunitrazepam; Na+/K+-ATPase; DMCM; Receptores glutamatérgicos; PEDIATRIA; Na+/K+-ATPase; DMCM; glutamatergic receptors; clonic convulsions

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Contó, M. B. (2008). Pharmacologycal and auto-radiographical study of GABAA/benzodiazepine site, and biochemical assays of the Na+/K+-ATPase and of the glutamatergic receptors in rats susceptible and non-susceptible to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist. (Thesis). Universidade Federal de São Paulo. Retrieved from http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2609 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2610

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Contó, Marcos Brandao. “Pharmacologycal and auto-radiographical study of GABAA/benzodiazepine site, and biochemical assays of the Na+/K+-ATPase and of the glutamatergic receptors in rats susceptible and non-susceptible to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist.” 2008. Thesis, Universidade Federal de São Paulo. Accessed January 20, 2021. http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2609 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2610.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Contó, Marcos Brandao. “Pharmacologycal and auto-radiographical study of GABAA/benzodiazepine site, and biochemical assays of the Na+/K+-ATPase and of the glutamatergic receptors in rats susceptible and non-susceptible to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist.” 2008. Web. 20 Jan 2021.

Vancouver:

Contó MB. Pharmacologycal and auto-radiographical study of GABAA/benzodiazepine site, and biochemical assays of the Na+/K+-ATPase and of the glutamatergic receptors in rats susceptible and non-susceptible to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist. [Internet] [Thesis]. Universidade Federal de São Paulo; 2008. [cited 2021 Jan 20]. Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2609 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2610.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Contó MB. Pharmacologycal and auto-radiographical study of GABAA/benzodiazepine site, and biochemical assays of the Na+/K+-ATPase and of the glutamatergic receptors in rats susceptible and non-susceptible to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist. [Thesis]. Universidade Federal de São Paulo; 2008. Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2609 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2610

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Gothenburg / Göteborgs Universitet

29. Svensson, Anders I. 1969-. Disinhibitory and aggressive behavior in the rat. Neurohumoral mechanisms.

Degree: 2000, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/14452

► Effective pharmacological treatment for impulsive aggression and dysfunctional impulsive behavior is needed. These behavioral disturbences in man and impulsive-like and aggressive behavior in animals may… (more)

▼ Effective pharmacological treatment for impulsive aggression and dysfunctional impulsive behavior is needed. These behavioral disturbences in man and impulsive-like and aggressive behavior in animals may involve serotonin (5-HT), noradrenaline (NA), GABAA receptors and steroid hormones, e.g. testosterone. Depletion of 5-HT consistently produces impulsive-like behavior and, in most investigations, aggressive behavior in animals. Positive and negative GABAA receptor modulators produce impulsive-like behavior and inhibited behavior, respectively. Animals depleted of brain 5-HT are more sensitive to both these behavioral effects. Moreover, several lines of behavioral and neurochemical evidence indicate GABAA receptor antagonistic properties of naloxone.In the present study a punished conflict model was used to study impulsive-like behavior in adult male rats. Impulsive-like behavior in brain 5-HT depleted isolated rats, by means of intracerebroventricular treatment with 5,7-dihydroxytryptamine (5,7-DHT), was reduced by naloxone at doses that did not significantly affect the behavior in sham-lesioned controls. Amobarbital (a positive GABAA receptor modulator) reversed the behavioral effect of naloxone at a dose without effects per se. Moreover, naloxone and Ro 15-4513 (partial inverse benzodiazepine;BDZ agonist) reduced aggression in 5,7-DHT treated residents in a resident intruder test. Sham-depleted animals did not display aggressive behavior. Naloxone reduced GABA-induced 36Cl- uptake in corticohippocampal synaptoneurosomes and shifted the concentration-response curve for GABA-induced 36Cl- uptake to the right. Amobarbital and GABA, but not morphine or flumazenil (BDZ antagonist), reversed the antagonistic effect of naloxone on GABAA receptor function. Furthermore, gonadectomy in connection with the 5,7-DHT treatment reduced both impulsive-like behavior and GABA-induced 36Cl- uptake in synaptoneuro-somes in isolated rats. Testosterone substitution prevented both these effects. Gonadectomy did not affect the behavior in non-lesioned isolated animals. However, in group-housed rats, gonadectomy enhanced inhibited behavior. Testosterone treatment to intact group-housed rats during six, but not 14 days, produced impulsive-like behavior. Testosterone treated rats (14 days) displayed increased sensitivity for flunitrazepam (BDZ)-induced sedation and increased GABA-induced 36Cl- uptake in synaptoneuro-somes. On the other hand, gonadectomized rats were less sensitivity for diazepam (BDZ)-produced sedation and muscle relaxation/ataxia. Thus, naloxone or other weak negative GABAA receptor modulators may represent a new pharmacological principle for the treatment of dysfunctional impulsive behavior. The present data support the hypothesis that both endogenous and exogenous testosterone promote impulsive-like behavior and this effect of testosterone may involve increased activity at GABAA receptors. Clinical studies are warranted to investigate whether testosterone antagonists and/or 5-a-reductase inhibitors are beneficial in the…

Subjects/Keywords: Serotonin; GABAA receptor; testosterone; gonadectomy; impulsive behavior; aggression; conflict model; flunitrazepam; diazepam

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Svensson, A. I. 1. (2000). Disinhibitory and aggressive behavior in the rat. Neurohumoral mechanisms. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/14452

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Svensson, Anders I 1969-. “Disinhibitory and aggressive behavior in the rat. Neurohumoral mechanisms.” 2000. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed January 20, 2021. http://hdl.handle.net/2077/14452.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Svensson, Anders I 1969-. “Disinhibitory and aggressive behavior in the rat. Neurohumoral mechanisms.” 2000. Web. 20 Jan 2021.

Vancouver:

Svensson AI1. Disinhibitory and aggressive behavior in the rat. Neurohumoral mechanisms. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2000. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/2077/14452.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Svensson AI1. Disinhibitory and aggressive behavior in the rat. Neurohumoral mechanisms. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2000. Available from: http://hdl.handle.net/2077/14452

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Texas

30. Gargan, Lynn. Age-Dependent Effects Of Chronic GABAA Receptor Blockade In Barrel Cortex.

Degree: 2001, University of North Texas

URL: https://digital.library.unt.edu/ark:/67531/metadc2760/

► GABAA receptor binding is transiently increased in rat whisker barrels during the second postnatal week, at a time when neurons in the developing rat cortex… (more)

Subjects/Keywords: GABA – Receptors.; Rats – Nervous system.; GABAA receptor binding; Excitotoxic effects; Postnatal development

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gargan, L. (2001). Age-Dependent Effects Of Chronic GABAA Receptor Blockade In Barrel Cortex. (Thesis). University of North Texas. Retrieved from https://digital.library.unt.edu/ark:/67531/metadc2760/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gargan, Lynn. “Age-Dependent Effects Of Chronic GABAA Receptor Blockade In Barrel Cortex.” 2001. Thesis, University of North Texas. Accessed January 20, 2021. https://digital.library.unt.edu/ark:/67531/metadc2760/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gargan, Lynn. “Age-Dependent Effects Of Chronic GABAA Receptor Blockade In Barrel Cortex.” 2001. Web. 20 Jan 2021.

Vancouver:

Gargan L. Age-Dependent Effects Of Chronic GABAA Receptor Blockade In Barrel Cortex. [Internet] [Thesis]. University of North Texas; 2001. [cited 2021 Jan 20]. Available from: https://digital.library.unt.edu/ark:/67531/metadc2760/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gargan L. Age-Dependent Effects Of Chronic GABAA Receptor Blockade In Barrel Cortex. [Thesis]. University of North Texas; 2001. Available from: https://digital.library.unt.edu/ark:/67531/metadc2760/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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