subject:(Tonic Inhibition)

University of Toronto

1. Zurek, Agnieszka A. Increased Activity of GABA(A) Receptors Contributes to Postanesthetic Memory Deficits.

Degree: PhD, 2015, University of Toronto

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General anesthetics are widely used to allow patients to tolerate surgery and to sedate patients in intensive care units. Anesthesia causes long-term memory deficits in… (more)

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General anesthetics are widely used to allow patients to tolerate surgery and to sedate patients in intensive care units. Anesthesia causes long-term memory deficits in laboratory animals, suggesting it could contribute to memory loss in patients. However, the mechanisms underlying postanesthetic memory deficits are unknown. Most anesthetics cause neurodepression by allosterically increasing the activity of gamma-aminobutyric acid type A (GABA-A) receptors. In particular, positive allosteric modulation of alpha5 subunit-containing GABA-A (alpha5GABA-A) receptors contributes to the acute, amnestic effects of the anesthetic etomidate. Once the anesthetic has been eliminated, allosteric modulation of GABA-A receptors is rapidly reversed and it is assumed that GABA-A receptors do not contribute to memory deficits that persist after anesthesia. However, previous work from our lab suggests that alpha5GABA-A receptors may play a role in postanesthetic memory loss, as treatment with a drug that inhibits these receptors before anesthesia prevents memory deficits. I hypothesized that exposure to anesthetics results in a sustained increase in alpha5GABA-A receptor activity, which causes memory deficits. First, my data showed that alpha5GABA-A receptors are required for postanesthetic memory deficits as wild-type, but not Gabra5 null-mutant mice (Gabra5-/-), exhibit impaired memory performance on the object recognition memory task. These deficits are evident for 24 hours after isoflurane anesthesia and persist for up to 1 week after exposure to the injectable anesthetic etomidate. The mechanism underlying these memory deficits is likely a sustained increase in the function of alpha5GABA-A receptors as a single, in vivo exposure to the anesthetic etomidate (8 mg/kg i.p.) or isoflurane (1.3%, 1 h) increases a tonic inhibitory current that is mediated by alpha5GABAA receptors and increases cell-surface expression of alpha5GABA-A receptors for least 1 week with full recovery by 2 weeks. Memory deficits in wild-type mice are reversed after anesthesia by inhibiting alpha5GABA-A receptor activity with the inverse agonist L-655,708. Collectively, these results refute the widely-held belief that the function of GABA-A receptors returns to baseline after the anesthetic agent has been eliminated. Furthermore, the data present a mechanism and a plausible treatment strategy for postanesthetic memory deficits.

2017-06-30 00:00:00

Advisors/Committee Members: Orser, Beverley A, Physiology.

Subjects/Keywords: Anesthesia; GABA; Memory; tonic inhibition; 0317

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

APA (6^th Edition):

Zurek, A. A. (2015). Increased Activity of GABA(A) Receptors Contributes to Postanesthetic Memory Deficits. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/77714

Chicago Manual of Style (16^th Edition):

Zurek, Agnieszka A. “Increased Activity of GABA(A) Receptors Contributes to Postanesthetic Memory Deficits.” 2015. Doctoral Dissertation, University of Toronto. Accessed March 03, 2021. http://hdl.handle.net/1807/77714.

MLA Handbook (7^th Edition):

Zurek, Agnieszka A. “Increased Activity of GABA(A) Receptors Contributes to Postanesthetic Memory Deficits.” 2015. Web. 03 Mar 2021.

Vancouver:

Zurek AA. Increased Activity of GABA(A) Receptors Contributes to Postanesthetic Memory Deficits. [Internet] [Doctoral dissertation]. University of Toronto; 2015. [cited 2021 Mar 03]. Available from: http://hdl.handle.net/1807/77714.

Council of Science Editors:

Zurek AA. Increased Activity of GABA(A) Receptors Contributes to Postanesthetic Memory Deficits. [Doctoral Dissertation]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/77714

UCLA

2. 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 (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 March 03, 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. 03 Mar 2021.

Vancouver:

Ferando I. Plasticity of GABAergic Inhibition. [Internet] [Thesis]. UCLA; 2014. [cited 2021 Mar 03]. 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

University of Toronto

3. Haffey, Sean Christopher. Probing the Role of Astrocytes in Postanesthetic Memory Deficits.

Degree: 2015, University of Toronto

URL: http://hdl.handle.net/1807/74727

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Many patients who undergo surgery and general anesthesia suffer from memory impairments for weeks to months afterwards. However, the mechanisms underlying this phenomenon remain poorly… (more)

Subjects/Keywords: Astrocytes; Electrophysiology; Etomidate; GABA; Hippocampus; Tonic Inhibition; 0719

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

APA (6^th Edition):

Haffey, S. C. (2015). Probing the Role of Astrocytes in Postanesthetic Memory Deficits. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/74727

Chicago Manual of Style (16^th Edition):

Haffey, Sean Christopher. “Probing the Role of Astrocytes in Postanesthetic Memory Deficits.” 2015. Masters Thesis, University of Toronto. Accessed March 03, 2021. http://hdl.handle.net/1807/74727.

MLA Handbook (7^th Edition):

Haffey, Sean Christopher. “Probing the Role of Astrocytes in Postanesthetic Memory Deficits.” 2015. Web. 03 Mar 2021.

Vancouver:

Haffey SC. Probing the Role of Astrocytes in Postanesthetic Memory Deficits. [Internet] [Masters thesis]. University of Toronto; 2015. [cited 2021 Mar 03]. Available from: http://hdl.handle.net/1807/74727.

Council of Science Editors:

Haffey SC. Probing the Role of Astrocytes in Postanesthetic Memory Deficits. [Masters Thesis]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/74727

Penn State University

4. Pitre, Anar. Modulation of epileptiform activity by activation of tonic inhibition .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8212

► The majority of the inhibition in the brain is mediated by GABA-A receptors. Synaptic GABA-A receptors enforce a strong, activity dependent inhibition, known as phasic… (more)

Subjects/Keywords: epilepsy; THIP; tonic inhibition; CTZ; GABA

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

APA (6^th Edition):

Pitre, A. (2008). Modulation of epileptiform activity by activation of tonic inhibition . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8212

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):

Pitre, Anar. “Modulation of epileptiform activity by activation of tonic inhibition .” 2008. Thesis, Penn State University. Accessed March 03, 2021. https://submit-etda.libraries.psu.edu/catalog/8212.

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

MLA Handbook (7^th Edition):

Pitre, Anar. “Modulation of epileptiform activity by activation of tonic inhibition .” 2008. Web. 03 Mar 2021.

Vancouver:

Pitre A. Modulation of epileptiform activity by activation of tonic inhibition . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 03]. Available from: https://submit-etda.libraries.psu.edu/catalog/8212.

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

Council of Science Editors:

Pitre A. Modulation of epileptiform activity by activation of tonic inhibition . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8212

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

Penn State University

5. 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 March 03, 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. 03 Mar 2021.

Vancouver:

Wu X. Targeting and function of extrasynaptic GABAA receptors. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Mar 03]. 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

Johannes Gutenberg Universität Mainz

6. Sattler, Christian. Assemblierung und Stöchiometrie von GABA-A-Rezeptoren : Bedeutung einzelner Untereinheiten in einem pentameren Komplex.

Degree: 2015, Johannes Gutenberg Universität Mainz

URL: http://ubm.opus.hbz-nrw.de/volltexte/2015/4172/

► Im Rahmen des Promotionsprojektes wurden a1,4,6-enthaltende GABAA-Rezeptoren in den Kombinationen ab3X (X= b3, g2, d) mit Hilfe der Patch-Clamp-Technik charakterisiert. Dazu wurde ein Set an… (more)

Subjects/Keywords: GABA; Patch-Clamp; Konkatamere; Subtypselektivität; tonische Inhibition; GABA; Patch-Clamp; Concatamers; Subtypselektivity; tonic Inhibition; Chemistry and allied sciences

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

APA (6^th Edition):

Sattler, C. (2015). Assemblierung und Stöchiometrie von GABA-A-Rezeptoren : Bedeutung einzelner Untereinheiten in einem pentameren Komplex. (Doctoral Dissertation). Johannes Gutenberg Universität Mainz. Retrieved from http://ubm.opus.hbz-nrw.de/volltexte/2015/4172/

Chicago Manual of Style (16^th Edition):

Sattler, Christian. “Assemblierung und Stöchiometrie von GABA-A-Rezeptoren : Bedeutung einzelner Untereinheiten in einem pentameren Komplex.” 2015. Doctoral Dissertation, Johannes Gutenberg Universität Mainz. Accessed March 03, 2021. http://ubm.opus.hbz-nrw.de/volltexte/2015/4172/.

MLA Handbook (7^th Edition):

Sattler, Christian. “Assemblierung und Stöchiometrie von GABA-A-Rezeptoren : Bedeutung einzelner Untereinheiten in einem pentameren Komplex.” 2015. Web. 03 Mar 2021.

Vancouver:

Sattler C. Assemblierung und Stöchiometrie von GABA-A-Rezeptoren : Bedeutung einzelner Untereinheiten in einem pentameren Komplex. [Internet] [Doctoral dissertation]. Johannes Gutenberg Universität Mainz; 2015. [cited 2021 Mar 03]. Available from: http://ubm.opus.hbz-nrw.de/volltexte/2015/4172/.

Council of Science Editors:

Sattler C. Assemblierung und Stöchiometrie von GABA-A-Rezeptoren : Bedeutung einzelner Untereinheiten in einem pentameren Komplex. [Doctoral Dissertation]. Johannes Gutenberg Universität Mainz; 2015. Available from: http://ubm.opus.hbz-nrw.de/volltexte/2015/4172/

7. Angelhuber, Martin. The neural circuitry of fear conditioning : a theoretical account : Le circuit neuronal du conditionnement à la peur : une perspective théorique.

Degree: Docteur es, Neurosciences, 2016, Strasbourg; Albert-Ludwigs-Universität (Fribourg-en-Brisgau, Allemagne); Universität Basel

URL: http://www.theses.fr/2016STRAJ082

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Conditionnement à la peur est un paradigme réussi pour comprendre les substrats neuronaux de l’apprentissage et de l’émotion. Dans cette thèse, je présente deux modèles… (more)

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Conditionnement à la peur est un paradigme réussi pour comprendre les substrats neuronaux de l’apprentissage et de l’émotion. Dans cette thèse, je présente deux modèles informatiques des structures du cerveau qui sous-tendent l'acquisition de la peur conditionnée. Le première modèle est utilisé pour enquêter sur l’effet des changements de l’inhibition tonique sur le traitement des informations reçues. On confirme que la diminution de l’inhibition tonique d’une population augmente la réactivité du réseau. Ensuite, le modèle est analysé d’une perspective fonctionnelle et des prédictions qui découlent de cette proposition sont discutées. En outre, je présenterai un modèle systématique, basé sur un type de modèle de conditionnement récemment introduit utilisant des variables latentes. Je propose que l’interaction entre les neurones dans l’amygdale basale code pour l’interface entre ces variables latentes. Le modèle couvre une large gamme d’effets et l’analyse produit un certain nombre de prédictions vérifiables.

Fear conditioning is a successful paradigm for studying neural substrates of emotional learning. In this thesis, two computational models of the underlying neural circuitry are presented. First, the effects of changes in neuronal membrane conductance on input processing are analyzed in a biologically realistic model. We show that changes in tonic inhibitory conductance increase the responsiveness of the network to inputs. Then, the model is analyzed from a functional perspective and predictions that follow from this proposition are discussed. Next, a systems level model is presented based on a recent high-level approach to conditioning. It is proposed that the interaction between fear and extinction neurons in the basal amygdala is a neural substrate of the switching between latent states, allowing the animal to infer causal structure. Important behavioral and physiological results are reproduced and predictions and questions that follow from the main hypothesis are considered.

Advisors/Committee Members: Veinante, Pierre (thesis director), Aertsen, Ad (thesis director), Lüthi, Andreas (thesis director).

Subjects/Keywords: Modèle informatique; Amygdale; Conditionnement à la peur; Inhibition tonique; Computational model; Amygdala; Fear conditioning; Tonic inhibition; 573.7; 616.8

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

APA (6^th Edition):

Angelhuber, M. (2016). The neural circuitry of fear conditioning : a theoretical account : Le circuit neuronal du conditionnement à la peur : une perspective théorique. (Doctoral Dissertation). Strasbourg; Albert-Ludwigs-Universität (Fribourg-en-Brisgau, Allemagne); Universität Basel. Retrieved from http://www.theses.fr/2016STRAJ082

Chicago Manual of Style (16^th Edition):

Angelhuber, Martin. “The neural circuitry of fear conditioning : a theoretical account : Le circuit neuronal du conditionnement à la peur : une perspective théorique.” 2016. Doctoral Dissertation, Strasbourg; Albert-Ludwigs-Universität (Fribourg-en-Brisgau, Allemagne); Universität Basel. Accessed March 03, 2021. http://www.theses.fr/2016STRAJ082.

MLA Handbook (7^th Edition):

Angelhuber, Martin. “The neural circuitry of fear conditioning : a theoretical account : Le circuit neuronal du conditionnement à la peur : une perspective théorique.” 2016. Web. 03 Mar 2021.

Vancouver:

Angelhuber M. The neural circuitry of fear conditioning : a theoretical account : Le circuit neuronal du conditionnement à la peur : une perspective théorique. [Internet] [Doctoral dissertation]. Strasbourg; Albert-Ludwigs-Universität (Fribourg-en-Brisgau, Allemagne); Universität Basel; 2016. [cited 2021 Mar 03]. Available from: http://www.theses.fr/2016STRAJ082.

Council of Science Editors:

Angelhuber M. The neural circuitry of fear conditioning : a theoretical account : Le circuit neuronal du conditionnement à la peur : une perspective théorique. [Doctoral Dissertation]. Strasbourg; Albert-Ludwigs-Universität (Fribourg-en-Brisgau, Allemagne); Universität Basel; 2016. Available from: http://www.theses.fr/2016STRAJ082

University of Illinois – Chicago

8. Widmer, Andrew Mark. Inhibitory Function in the Olfactory Cortex of a Mouse Model of Fragile X Syndrome.

Degree: 2019, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/23873

► Presented here are a series of four single-cell electrophysiology experiments detailing the function of inhibitory and excitatory processes in the anterior piriform cortex. The normal… (more)

▼ Presented here are a series of four single-cell electrophysiology experiments detailing the function of inhibitory and excitatory processes in the anterior piriform cortex. The normal function and neurophysiology of this area is contrasted with that of a mouse model of the genetic disorder Fragile X Syndrome, a pleiotropic disorder that is hypothesized to be characterized by improper excitatory/inhibitory balance in a number of brain regions. Analysis of quantal inhibitory neurotransmission provided the most comprehensive report of synaptic inhibition in the piriform cortex to date. This study revealed no deficit in the synaptic properties of Fragile X Syndrome mice. Event amplitude, shape statistics, and interevent timing parameters were all in close agreement between the two groups. Tonic inhibitory conductance was found to be comparable between genotypes as well, in contrast to several published reports of compromised tonic inhibition in this disease model. A measure of the cellular response to evoked stimulation was performed, testing the function of a known fast inhibitory microcircuit. This experiment showed that both Fragile X Syndrome and control animals exhibit tight inhibitory control of evoked excitation at moderate and high stimulation levels. Additionally, a paired pulse test demonstrated that, while excitatory currents increase in response to quickly arriving stimuli, feedforward inhibition scales as well, maintaining the inhibitory/excitatory balance. The cellular response to bursting stimulation was assessed for each genotype at a holding potential of -70mV and at the native resting membrane potential for each cell, both in the absence and presence of pharmacological blockade of NMDA-type glutamatergic receptors. A significant deficit in NMDA receptor-mediated current was observed in the burst response of Fragile X Syndrome cells but not in controls. It was also shown in control animals that NMDA receptors participate in the excitatory response to a single burst of stimuli, an unexpected finding that suggests unique integrative processes in the anterior piriform cortex with respect to homologous brain structures. Advisors/Committee Members: Larson, John R (advisor), Loeb, Jeffrey (committee member), Leonard, John (committee member), Berry-Kravis, Elizabeth (committee member), Brodie, Mark (chair).

Subjects/Keywords: FXS; Fragile X Syndrome; plasticity; potentiation; LTP; LTD; inhibition; tonic inhibition; GABA; GABAa; GABAR; NMDA; NMDAR; inhibition/excitation; piriform; olfactory; piriform cortex; olfactory cortex; intellectual disability; mouse model; seizure; epilepsy

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APA (6^th Edition):

Widmer, A. M. (2019). Inhibitory Function in the Olfactory Cortex of a Mouse Model of Fragile X Syndrome. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/23873

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):

Widmer, Andrew Mark. “Inhibitory Function in the Olfactory Cortex of a Mouse Model of Fragile X Syndrome.” 2019. Thesis, University of Illinois – Chicago. Accessed March 03, 2021. http://hdl.handle.net/10027/23873.

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

MLA Handbook (7^th Edition):

Widmer, Andrew Mark. “Inhibitory Function in the Olfactory Cortex of a Mouse Model of Fragile X Syndrome.” 2019. Web. 03 Mar 2021.

Vancouver:

Widmer AM. Inhibitory Function in the Olfactory Cortex of a Mouse Model of Fragile X Syndrome. [Internet] [Thesis]. University of Illinois – Chicago; 2019. [cited 2021 Mar 03]. Available from: http://hdl.handle.net/10027/23873.

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

Council of Science Editors:

Widmer AM. Inhibitory Function in the Olfactory Cortex of a Mouse Model of Fragile X Syndrome. [Thesis]. University of Illinois – Chicago; 2019. Available from: http://hdl.handle.net/10027/23873

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

9. Chazalon, Marine. Caractérisation de la transmission GABAergique dans le globus pallidus externe chez des modèles rongeurs des maladies de Parkinson et de Huntington : Investigation of GABAergic neurotransmission in the external globus pallidus in rodent models of Parkinson and huntington’s diseases.

Degree: Docteur es, Neurosciences, 2015, Bordeaux

URL: http://www.theses.fr/2015BORD0310

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Les ganglions de la base (GB) sont un ensemble de noyaux sous-corticaux impliqués dans les fonctions motrices, mnésiques et cognitives. Le globus pallidus externe (GPe)… (more)

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Les ganglions de la base (GB) sont un ensemble de noyaux sous-corticaux impliqués dans les fonctions motrices, mnésiques et cognitives. Le globus pallidus externe (GPe) est un noyau GABAergique, qui tient la place de structure relais entre le striatum et le noyau sous-thalamique au sein du réseau des GB. Les changements de mode et de fréquence de décharge des neurones du GPe sont connus pour être les signatures électro-physiologiques des maladies de Parkinson (MP) et de Huntington (MH). Dans la MP, où les concentrations de GABA extracellulaires sont anormalement élevées dans le GPe, il est admis que la voie striato-pallidale (STR-GPe) est hyperactive, ce qui contribue à l’hypoactivité des neurones pallidaux. A l’inverse dans la MH, il est admis que l’hyperactivité des neurones du GPe est due à la dégénérescence de la voie STR-GPe levant la principale influence inhibitrice du GPe. Cependant, les mécanismes moléculaires impliqués dans ces changements d’activité pallidale sont encore peu connus. Nous avons donc entrepris des expériences de biologie moléculaire, d’immunohistochimie et d’électrophysiologie sur tranches, afin de mieux caractériser l’origine des modifications de transmission GABAergique conduisant aux changements d’activité électro-physiologique des neurones du GPe dans ces deux pathologies à l’aide de modèles animaux. Mes principaux résultats montrent l’apparition d’une inhibition tonique dans les neurones du GPe due à un déficit de recapture du GABA dans la MP et une réduction précoce de la transmission synaptique GABAergique dans la MH. Ces résultats suggèrent que les altérations de la transmission GABAergique contribuent à la physiopathologie de la MP et la MH.

The basal ganglia (BG) are a group of sub-cortical nuclei involved in motor, memory and cognitive functions. In the BG, the GABAergic external globus pallidus (GPe) holds a position of relay nucleus between the striatum (STR) and the sub thalamic nucleus within the indirect pathway of the BG. Modifications of rate and pattern of activity of this nucleus are known to be the electrophysiological signatures of Parkinson’s (PD) and Huntington’s diseases (HD). In PD, hyperactivity of the striato-pallidal (STR-GPe) pathway is thought to be responsible for the increase of the extracellular GABAergic concentrations in the GPe and participate to the hypoactivity of pallidal neurons observed in experimental Parkinsonism. In contrast, during HD, it is recognized that the hyperactivity of GPe neurons is due to the degeneration of striato-pallidal neurons and thus to the reduction of the main source of pallidal GABAergic inhibition. However, the molecular mechanisms involved in these modifications of pallidal activity are not well characterized. Therefore, using PD and HD animal models, the 6-OHDA rodents and the R6-1 transgenic mice respectively, we have performed molecular biology, immunohistochemistry and electrophysiological in vitro experiments in order to better understand the origin of GABAergic transmission alterations leading to changes in…

Advisors/Committee Members: Baufreton, Jérôme (thesis director).

Subjects/Keywords: Globus pallidus externe; Patch-clamp; Transmission synaptique; Inhibition tonique; Récepteurs GABAA extrasynaptiques; Transporteurs du GABA; Maladie de Parkinson; Maladie de Huntington; External globus pallidus; Patch-clamp; Synaptic transmission; Tonic inhibition; Extrasynaptic GABAA receptors; GABA transporters; Parkinson’s disease; Huntington’s disease

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

APA (6^th Edition):

Chazalon, M. (2015). Caractérisation de la transmission GABAergique dans le globus pallidus externe chez des modèles rongeurs des maladies de Parkinson et de Huntington : Investigation of GABAergic neurotransmission in the external globus pallidus in rodent models of Parkinson and huntington’s diseases. (Doctoral Dissertation). Bordeaux. Retrieved from http://www.theses.fr/2015BORD0310

Chicago Manual of Style (16^th Edition):

Chazalon, Marine. “Caractérisation de la transmission GABAergique dans le globus pallidus externe chez des modèles rongeurs des maladies de Parkinson et de Huntington : Investigation of GABAergic neurotransmission in the external globus pallidus in rodent models of Parkinson and huntington’s diseases.” 2015. Doctoral Dissertation, Bordeaux. Accessed March 03, 2021. http://www.theses.fr/2015BORD0310.

MLA Handbook (7^th Edition):

Chazalon, Marine. “Caractérisation de la transmission GABAergique dans le globus pallidus externe chez des modèles rongeurs des maladies de Parkinson et de Huntington : Investigation of GABAergic neurotransmission in the external globus pallidus in rodent models of Parkinson and huntington’s diseases.” 2015. Web. 03 Mar 2021.

Vancouver:

Chazalon M. Caractérisation de la transmission GABAergique dans le globus pallidus externe chez des modèles rongeurs des maladies de Parkinson et de Huntington : Investigation of GABAergic neurotransmission in the external globus pallidus in rodent models of Parkinson and huntington’s diseases. [Internet] [Doctoral dissertation]. Bordeaux; 2015. [cited 2021 Mar 03]. Available from: http://www.theses.fr/2015BORD0310.

Council of Science Editors:

Chazalon M. Caractérisation de la transmission GABAergique dans le globus pallidus externe chez des modèles rongeurs des maladies de Parkinson et de Huntington : Investigation of GABAergic neurotransmission in the external globus pallidus in rodent models of Parkinson and huntington’s diseases. [Doctoral Dissertation]. Bordeaux; 2015. Available from: http://www.theses.fr/2015BORD0310

10. Bonin, Robert. The Regulation of Neuronal Excitability and Nociception by Tonic GABAergic Inhibition.

Degree: 2012, University of Toronto

URL: http://hdl.handle.net/1807/35720

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The mammalian central nervous system maintains a delicate balance between neuronal excitation and inhibition. Conventional synaptic inhibition is mediated through the transient activity of postsynaptic… (more)

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The mammalian central nervous system maintains a delicate balance between neuronal excitation and inhibition. Conventional synaptic inhibition is mediated through the transient activity of postsynaptic γ-aminobutyric acid (GABA) at type A GABA (GABAA) receptors. A subset of GABAA receptors is also located outside of inhibitory synapses. These extrasynaptic receptors generate a tonic inhibitory conductance in response to low concentrations of extracellular GABA. Tonic inhibition broadly suppresses neuronal activity and regulates many vital processes such as sleep, consciousness and memory formation. This thesis examines the physiological effects of tonic inhibition at the cellular level and in the behaving animal. This thesis also explores whether gabapentin, a commonly used sedative, anxiolytic, and analgesic drug, enhances tonic GABAergic inhibition. I hypothesize that: (1) tonic GABAA receptor activity reduces the intrinsic excitability of neurons; (2) the activity of tonically active GABAA receptors in spinal pain pathways attenuates nociception; and (3) tonic inhibition can be upregulated by gabapentin. The results show that a tonic inhibitory current generated by α5 subunit-containing GABAA (α5GABAA) receptors reduces the excitability of hippocampal pyramidal neurons excitability by increasing the rheobase, but does not change the gain of action potential firing. A similar shunting inhibition is present in spinal cord lamina II neurons that is generated by δ subunit-containing GABAA receptors. The activity of these receptors in spinal nociceptive pathways reduces acute thermal nociception and may constrain central sensitization in a behavioural model of persistent pain. Finally, gabapentin increases a tonic inhibitory current in cultured hippocampal neurons independent from changes in the expression of α5GABAA receptors or in the concentration of GABAA receptor ligands. The results of this thesis demonstrate that tonically active GABAA receptors play an important role in the regulation of neuronal activity and nociception, and that tonic inhibition represents a novel target of therapeutic drugs.

PhD

Advisors/Committee Members: Orser, Beverley, Physiology.

Subjects/Keywords: GABA; neuronal excitability; dorsal horn; tonic inhibition; nociception; gabapentin; 0317; 0719

…89 5.3.2 Tonic inhibition regulates neuronal excitability… …157 8.1 Tonic inhibition of neuronal excitability… …157 8.1.1 Computational effects of tonic inhibition on hippocampal function… …8.2 The role of tonic inhibition in nociception… …164 8.2.2 Tonic inhibition of dorsal horn neurons by α5GABAA receptors…

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

APA (6^th Edition):

Bonin, R. (2012). The Regulation of Neuronal Excitability and Nociception by Tonic GABAergic Inhibition. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/35720

Chicago Manual of Style (16^th Edition):

Bonin, Robert. “The Regulation of Neuronal Excitability and Nociception by Tonic GABAergic Inhibition.” 2012. Doctoral Dissertation, University of Toronto. Accessed March 03, 2021. http://hdl.handle.net/1807/35720.

MLA Handbook (7^th Edition):

Bonin, Robert. “The Regulation of Neuronal Excitability and Nociception by Tonic GABAergic Inhibition.” 2012. Web. 03 Mar 2021.

Vancouver:

Bonin R. The Regulation of Neuronal Excitability and Nociception by Tonic GABAergic Inhibition. [Internet] [Doctoral dissertation]. University of Toronto; 2012. [cited 2021 Mar 03]. Available from: http://hdl.handle.net/1807/35720.

Council of Science Editors:

Bonin R. The Regulation of Neuronal Excitability and Nociception by Tonic GABAergic Inhibition. [Doctoral Dissertation]. University of Toronto; 2012. Available from: http://hdl.handle.net/1807/35720

Université de Montréal

11. Atallah, Elias. Transmission des voies olfactives aux cellules réticulospinales de la lamproie.

Degree: 2012, Université de Montréal

URL: http://hdl.handle.net/1866/7056

Subjects/Keywords: Transformation olfacto-locomotrice; nerf olfactif; bulbe olfactif; tubercule postérieur; région locomotrice mésencéphalique; neurones réticulospinaux; tonus inhibiteur; lamproie; électrophysiologie; imagerie calcique; Olfactory-locomotor transformation; olfactory nerve; olfactory bulb; posterior tuberculum; mesencephalic locomotor region; reticulospinal neurons; tonic inhibition; lamprey; electrophysiology; calcium imaging; Biology - Physiology / Biologie - Physiologie (UMI : 0719)

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):

Atallah, E. (2012). Transmission des voies olfactives aux cellules réticulospinales de la lamproie. (Thesis). Université de Montréal. Retrieved from http://hdl.handle.net/1866/7056

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):

Atallah, Elias. “Transmission des voies olfactives aux cellules réticulospinales de la lamproie.” 2012. Thesis, Université de Montréal. Accessed March 03, 2021. http://hdl.handle.net/1866/7056.

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

MLA Handbook (7^th Edition):

Atallah, Elias. “Transmission des voies olfactives aux cellules réticulospinales de la lamproie.” 2012. Web. 03 Mar 2021.

Vancouver:

Atallah E. Transmission des voies olfactives aux cellules réticulospinales de la lamproie. [Internet] [Thesis]. Université de Montréal; 2012. [cited 2021 Mar 03]. Available from: http://hdl.handle.net/1866/7056.

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

Council of Science Editors:

Atallah E. Transmission des voies olfactives aux cellules réticulospinales de la lamproie. [Thesis]. Université de Montréal; 2012. Available from: http://hdl.handle.net/1866/7056

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

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Open Access Theses and Dissertations