+publisher:"Princeton University" +contributor:("Gould, Elizabeth")

Princeton University

1. Briones, Brandy Angeline. INVESTIGATING STRUCTURAL PLASTICITY AND PERINEURONAL NETS IN THE HIPPOCAMPUS AND DORSAL STRIATUM .

Degree: PhD, 2020, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp01xw42nb95b

► My dissertation work investigates dentate gyrus and dorsal striatum-dependent plasticity, specifically to better understand inhibitory neurons and perineuronal nets (PNNs), specialized extracellular matrix structures. These… (more)

▼ My dissertation work investigates dentate gyrus and dorsal striatum-dependent plasticity, specifically to better understand inhibitory neurons and perineuronal nets (PNNs), specialized extracellular matrix structures. These structures have been studied extensively within the developing visual cortex and are typically thought of as molecular restraints on structural and synaptic plasticity, but it is unknown what role, if any, PNNs play in regions exhibiting high degrees of experience-dependent plasticity throughout adulthood. In the dentate gyrus, we investigated adult-born granule cell (abGC) projections onto GABAergic inhibitory parvalbumin (PV+) interneurons, many of which are enwrapped in PNNs, and discovered that abGC mossy fibers and boutons are more often associated with PV+PNN+ interneurons. These results, while unexpected, suggest a more complex region-specific role for PNNs in the adult mammalian brain. To further investigate this possibility, we turned to the dorsal striatum, a region we have demonstrated exhibits experience-dependent structural plasticity in medium spiny neurons (MSNs). To understand how PNNs influence inhibitory signaling and linked behaviors, we examined PNN-expression in the dorsomedial striatum (DMS) of four mouse strains known to lack behavioral flexibility and exhibit robust phenotypes for excessive repetitive behavior. Across all strains, we observed consistent over-expression of PNNs surrounding PV+ interneurons, further implicating PNNs involvement in mechanisms of inhibitory plasticity. Furthermore, we found that reducing PNN-expression subsequently reduces excessive repetitive behaviors. To characterize the effects of increased PNNs on inhibitory signaling, we investigated various electrophysiological and structural properties of DMS MSNs. Mice with increased PNNs showed decreased MSN dendritic spines and altered inhibitory signaling compared to healthy controls, and while reduction of DMS PNNs altered inhibitory signaling, it did not “normalize” it. These findings additionally suggest that an overabundance of PNNs in the DMS prevent adaptive disengagement from repetitive behaviors, potentially through abnormal inhibitory signaling, but further studies are required to identify the mechanisms in which PNNs might gate this behavior. These studies taken together demonstrate that PNNs play complex roles that differ depending on brain region; hippocampal PNNs participate in structural plasticity via connectivity from abGCs, and conversely, DMS PNNs are related to mechanisms of behavioral rigidity in mouse models of excessive repetitive behaviors. Advisors/Committee Members: Gould, Elizabeth (advisor).

Subjects/Keywords: adult neurogenesis; hippocampus; inhibitory neurons; perineuronal nets; plasticity; striatum

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Briones, B. A. (2020). INVESTIGATING STRUCTURAL PLASTICITY AND PERINEURONAL NETS IN THE HIPPOCAMPUS AND DORSAL STRIATUM . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp01xw42nb95b

Chicago Manual of Style (16^th Edition):

Briones, Brandy Angeline. “INVESTIGATING STRUCTURAL PLASTICITY AND PERINEURONAL NETS IN THE HIPPOCAMPUS AND DORSAL STRIATUM .” 2020. Doctoral Dissertation, Princeton University. Accessed January 16, 2021. http://arks.princeton.edu/ark:/88435/dsp01xw42nb95b.

MLA Handbook (7^th Edition):

Briones, Brandy Angeline. “INVESTIGATING STRUCTURAL PLASTICITY AND PERINEURONAL NETS IN THE HIPPOCAMPUS AND DORSAL STRIATUM .” 2020. Web. 16 Jan 2021.

Vancouver:

Briones BA. INVESTIGATING STRUCTURAL PLASTICITY AND PERINEURONAL NETS IN THE HIPPOCAMPUS AND DORSAL STRIATUM . [Internet] [Doctoral dissertation]. Princeton University; 2020. [cited 2021 Jan 16]. Available from: http://arks.princeton.edu/ark:/88435/dsp01xw42nb95b.

Council of Science Editors:

Briones BA. INVESTIGATING STRUCTURAL PLASTICITY AND PERINEURONAL NETS IN THE HIPPOCAMPUS AND DORSAL STRIATUM . [Doctoral Dissertation]. Princeton University; 2020. Available from: http://arks.princeton.edu/ark:/88435/dsp01xw42nb95b

2. Borjon, Jeremy Isaac. AUTONOMIC NERVOUS SYSTEM DYNAMICS AND PRIMATE VOCAL PRODUCTION .

Degree: PhD, 2017, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp01b5644v14s

► In humans, vocal production is typically cast as a cognitively intensive process, requiring a big brain and complex cognitive mechanisms. Recent studies have demonstrated that… (more)

▼ In humans, vocal production is typically cast as a cognitively intensive process, requiring a big brain and complex cognitive mechanisms. Recent studies have demonstrated that the vocal behavior of marmoset monkeys, a diminutive New World primate, is strikingly human-like in its dynamics and development. Considering the evolutionary gap between species, any shared neural mechanisms should be quite old. We propose that the convergent evolution of vocal behavior between marmosets and humans is partly due to neural mechanisms scaffolding upon a pre-existing arousal-regulation mechanism. We directly tested our hypothesis by recording natural changes in the adult marmoset’s arousal state as it spontaneously vocalized. We demonstrate predictable changes in the animal’s arousal state across multiple indices: heart rate, respiration rate, and motor activity. Moreover, the timing of vocal production in adult marmosets is coupled with the phase of a 0.1 Hz autonomic nervous system rhythm, the Mayer wave. The results of this study suggest that arousal dynamics are critical in assembling the timing and prediction of spontaneous primate vocalizations. We next sought to determine whether the dynamics of the autonomic nervous system can act as a scaffold for the development of behavior. We densely sampled indices of arousal, motor activity, and vocal behavior from seven infant marmosets from birth until two months of age. Consistent with the human literature, changes in motor activity are predictive of vocal development in marmoset monkeys. Further, the developmental trajectory of the autonomic nervous system is itself oscillatory and correlates to changes in both the infant’s vocal development and its motor development. We used statistical methods to extract causality between these processes. Changes in the development of the autonomic nervous system drives both the development of mature motor behavior and mature vocal production. Taken together, this dissertation argues that the autonomic nervous system is critical for the development and expression of spontaneous behavior in primates. Advisors/Committee Members: Ghazanfar, Asif A (advisor), Gould, Elizabeth (advisor).

Subjects/Keywords: Autonomic Nervous System; Development; Marmoset; Mayer wave; Primate; Vocal Production

10 more images…

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Borjon, J. I. (2017). AUTONOMIC NERVOUS SYSTEM DYNAMICS AND PRIMATE VOCAL PRODUCTION . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp01b5644v14s

Chicago Manual of Style (16^th Edition):

Borjon, Jeremy Isaac. “AUTONOMIC NERVOUS SYSTEM DYNAMICS AND PRIMATE VOCAL PRODUCTION .” 2017. Doctoral Dissertation, Princeton University. Accessed January 16, 2021. http://arks.princeton.edu/ark:/88435/dsp01b5644v14s.

MLA Handbook (7^th Edition):

Borjon, Jeremy Isaac. “AUTONOMIC NERVOUS SYSTEM DYNAMICS AND PRIMATE VOCAL PRODUCTION .” 2017. Web. 16 Jan 2021.

Vancouver:

Borjon JI. AUTONOMIC NERVOUS SYSTEM DYNAMICS AND PRIMATE VOCAL PRODUCTION . [Internet] [Doctoral dissertation]. Princeton University; 2017. [cited 2021 Jan 16]. Available from: http://arks.princeton.edu/ark:/88435/dsp01b5644v14s.

Council of Science Editors:

Borjon JI. AUTONOMIC NERVOUS SYSTEM DYNAMICS AND PRIMATE VOCAL PRODUCTION . [Doctoral Dissertation]. Princeton University; 2017. Available from: http://arks.princeton.edu/ark:/88435/dsp01b5644v14s

Princeton University

3. Choi, Jung Yoon. The Role of Acetylcholine and Dopamine in Working Memory .

Degree: PhD, 2019, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp01d791sk04k

► Working memory, the ability to remember a stimulus for a brief period of time and to use that memory flexibly to guide ongoing behavior, is… (more)

▼ Working memory, the ability to remember a stimulus for a brief period of time and to use that memory flexibly to guide ongoing behavior, is a ubiquitous function essential to our cognition. In this thesis, I investigate the temporally-precise role of two major neuromodulatory systems - midbrain dopaminergic (DA) system and basal forebrain cholinergic (ChAT) system- in spatial working memory. In the first study, the role of ChAT system in working memory is examined. Using delayed non-match to position task (DNMTP) as a behavioral assay to probe rodent spatial working memory, I first quantitatively demonstrate that animals’ locomotion explains more variance in medial septum (MS) ChAT neurons than task events while task events explains more variance in nucleus basalis (NB) ChAT neurons than locomotion, establishing two distinct roles of these ChAT brain regions in subserving DNMTP task. Furthermore, I show that NB ChAT neurons respond to lever press action and reward, and this task event encoding is spatially organized along the medio- lateral axis of the NB. Lastly, I report that these ChAT neurons in the NB are surprisingly integrated within the basal ganglia in a topographical fashion, providing an anatomical substrate to the functional heterogeneity in the NB ChAT neurons. In the second study, the role of DA system in working memory is investigated using the same working memory task. I first quantitatively show that task events such as lever presentation cue and reward, are encoded with phasic elevated activity, similarly between DA neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). In contrast, SNc and VTA DA neurons are relatively depressed during the delay period. Next, I present a series of causal, optogenetic experiments to test a set of predictions outlined by the “gating” theory and “inverted- U-shape” hypothesis of DA in working memory. We demonstrate that bi-directional manipulation of VTA DA neurons during the sample and delay period impairs the cognitive component of the task supporting the “inverted-U-shape” hypothesis, while SNc DA neurons may be more involved in the motor execution of the task. This is the first evidence providing dissociable causal roles of VTA and SNc DA neurons in working memory. Advisors/Committee Members: Witten, Ilana B (advisor), Gould, Elizabeth (advisor).

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Choi, J. Y. (2019). The Role of Acetylcholine and Dopamine in Working Memory . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp01d791sk04k

Chicago Manual of Style (16^th Edition):

Choi, Jung Yoon. “The Role of Acetylcholine and Dopamine in Working Memory .” 2019. Doctoral Dissertation, Princeton University. Accessed January 16, 2021. http://arks.princeton.edu/ark:/88435/dsp01d791sk04k.

MLA Handbook (7^th Edition):

Choi, Jung Yoon. “The Role of Acetylcholine and Dopamine in Working Memory .” 2019. Web. 16 Jan 2021.

Vancouver:

Choi JY. The Role of Acetylcholine and Dopamine in Working Memory . [Internet] [Doctoral dissertation]. Princeton University; 2019. [cited 2021 Jan 16]. Available from: http://arks.princeton.edu/ark:/88435/dsp01d791sk04k.

Council of Science Editors:

Choi JY. The Role of Acetylcholine and Dopamine in Working Memory . [Doctoral Dissertation]. Princeton University; 2019. Available from: http://arks.princeton.edu/ark:/88435/dsp01d791sk04k

Princeton University

4. Choi, Jung Yoon. The Role of Acetylcholine and Dopamine in Working Memory .

Degree: PhD, 2019, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp01zk51vk657

► Working memory, the ability to remember a stimulus for a brief period of time and to use that memory flexibly to guide ongoing behavior, is… (more)

▼ Working memory, the ability to remember a stimulus for a brief period of time and to use that memory flexibly to guide ongoing behavior, is a ubiquitous function essential to our cognition. In this thesis, I investigate the temporally-precise role of two major neuromodulatory systems - midbrain dopaminergic (DA) system and basal forebrain cholinergic (ChAT) system- in spatial working memory. In the first study, the role of ChAT system in working memory is examined. Using delayed non-match to position task (DNMTP) as a behavioral assay to probe rodent spatial working memory, I first quantitatively demonstrate that animals’ locomotion explains more variance in medial septum (MS) ChAT neurons than task events while task events explains more variance in nucleus basalis (NB) ChAT neurons than locomotion, establishing two distinct roles of these ChAT brain regions in subserving DNMTP task. Furthermore, I show that NB ChAT neurons respond to lever press action and reward, and this task event encoding is spatially organized along the medio- lateral axis of the NB. Lastly, I report that these ChAT neurons in the NB are surprisingly integrated within the basal ganglia in a topographical fashion, providing an anatomical substrate to the functional heterogeneity in the NB ChAT neurons. In the second study, the role of DA system in working memory is investigated using the same working memory task. I first quantitatively show that task events such as lever presentation cue and reward, are encoded with phasic elevated activity, similarly between DA neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). In contrast, SNc and VTA DA neurons are relatively depressed during the delay period. Next, I present a series of causal, optogenetic experiments to test a set of predictions outlined by the “gating” theory and “inverted- U-shape” hypothesis of DA in working memory. We demonstrate that bi-directional manipulation of VTA DA neurons during the sample and delay period impairs the cognitive component of the task supporting the “inverted-U-shape” hypothesis, while SNc DA neurons may be more involved in the motor execution of the task. This is the first evidence providing dissociable causal roles of VTA and SNc DA neurons in working memory. Advisors/Committee Members: Witten, Ilana B (advisor), Gould, Elizabeth (advisor).

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Choi, J. Y. (2019). The Role of Acetylcholine and Dopamine in Working Memory . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp01zk51vk657

Chicago Manual of Style (16^th Edition):

Choi, Jung Yoon. “The Role of Acetylcholine and Dopamine in Working Memory .” 2019. Doctoral Dissertation, Princeton University. Accessed January 16, 2021. http://arks.princeton.edu/ark:/88435/dsp01zk51vk657.

MLA Handbook (7^th Edition):

Choi, Jung Yoon. “The Role of Acetylcholine and Dopamine in Working Memory .” 2019. Web. 16 Jan 2021.

Vancouver:

Choi JY. The Role of Acetylcholine and Dopamine in Working Memory . [Internet] [Doctoral dissertation]. Princeton University; 2019. [cited 2021 Jan 16]. Available from: http://arks.princeton.edu/ark:/88435/dsp01zk51vk657.

Council of Science Editors:

Choi JY. The Role of Acetylcholine and Dopamine in Working Memory . [Doctoral Dissertation]. Princeton University; 2019. Available from: http://arks.princeton.edu/ark:/88435/dsp01zk51vk657

5. Schoenfeld, Timothy James. Mechanisms Underlying the Anxiolytic Actions of Physical Exercise .

Degree: PhD, 2012, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp010r967376j

► Exercise reduces anxiety in both humans and rodents. Understanding the mechanisms underlying the anxiolytic actions of exercise may provide clues to novel treatments for individuals… (more)

▼ Exercise reduces anxiety in both humans and rodents. Understanding the mechanisms underlying the anxiolytic actions of exercise may provide clues to novel treatments for individuals with anxiety disorders. To investigate potential mechanisms underlying anxiety, my dissertation focused on the ventral hippocampus, an anxiogenic region that is highly susceptible to neuronal changes due to long-term running. My first series of experiments showed that in sedentary mice, stress activated new and preexisting granule neurons in the ventral hippocampus. Long-term running, which dramatically increases the production of granule neurons in the dentate gyrus of the hippocampus, prevented the stress-induced activation of new and preexisting granule neurons in the ventral hippocampus. Next, I investigated whether stress alters GABAergic mechanisms differentially in the hippocampus of runner and sedentary mice. I observed that runners have greater stress-induced activation of GABAergic inhibitory interneurons in the ventral hippocampus. I found that runners had greater levels of the presynaptic vesicular GABA transporter and increased GABA release in the hippocampus during stress. These findings suggest that despite having increased numbers of new excitatory neurons in the hippocampus, runners show reduced activation of these cells, most likely because of enhanced activity in local GABAergic interneurons. In addition, direct infusion of the GABA-A receptor antagonist bicuculline into the ventral hippocampus reversed the anxiolytic effect of running in mice, suggesting that GABA signaling mediates the anxiolytic actions of exercise. Finally, I examined whether gap junctions among GABAergic interneurons in the ventral hippocampus are important for anxiety regulation. I found that gap junction inhibitors injected peripherally and infused directly into the ventral hippocampus reduced anxiety-like behavior. Blocking gap junctions in the ventral hippocampus unilaterally and in the medial prefrontal cortex on the other hemisphere also reduced anxiety-like behavior, suggesting that gap junction-mediated signaling in the ventral hippocampus and medial prefrontal cortex may drive anxiety-like behavior in mice. Running decreased the expression of connexin-36, a critical component of neuronal gap junctions, in hippocampal interneurons, suggesting that reduced anxiety-like behavior in runners may occur through decreased gap junction signaling. Overall, my results suggest that although running stimulates the proliferation of new neurons in the ventral hippocampus, heightened GABAergic function in runners prevents the activation of these new neurons in response to stress. Increased GABAergic signaling and decreases gap junction-mediated signaling within the ventral hippocampus of runners may mediate running-induced decreases in anxiety-like behavior in mice. Advisors/Committee Members: Gould, Elizabeth (advisor).

Subjects/Keywords: Anxiety; GABA; Gap Junctions; Hippocampus; Neurogenesis; Running

…Methods. Animal treatments All experiments were carried out in compliance with the Princeton… …University Institutional Animal Care and Use Committee and the US National Institutes of Health…

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Schoenfeld, T. J. (2012). Mechanisms Underlying the Anxiolytic Actions of Physical Exercise . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp010r967376j

Chicago Manual of Style (16^th Edition):

Schoenfeld, Timothy James. “Mechanisms Underlying the Anxiolytic Actions of Physical Exercise .” 2012. Doctoral Dissertation, Princeton University. Accessed January 16, 2021. http://arks.princeton.edu/ark:/88435/dsp010r967376j.

MLA Handbook (7^th Edition):

Schoenfeld, Timothy James. “Mechanisms Underlying the Anxiolytic Actions of Physical Exercise .” 2012. Web. 16 Jan 2021.

Vancouver:

Schoenfeld TJ. Mechanisms Underlying the Anxiolytic Actions of Physical Exercise . [Internet] [Doctoral dissertation]. Princeton University; 2012. [cited 2021 Jan 16]. Available from: http://arks.princeton.edu/ark:/88435/dsp010r967376j.

Council of Science Editors:

Schoenfeld TJ. Mechanisms Underlying the Anxiolytic Actions of Physical Exercise . [Doctoral Dissertation]. Princeton University; 2012. Available from: http://arks.princeton.edu/ark:/88435/dsp010r967376j

6. Opendak, Maya. Social instability, hippocampal plasticity and resilience .

Degree: PhD, 2015, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp013197xp36d

► Experience-dependent changes in the production and function of new neurons may serve as a means to fine-tune the hippocampus to the predicted environment. Here we… (more)

▼ Experience-dependent changes in the production and function of new neurons may serve as a means to fine-tune the hippocampus to the predicted environment. Here we describe a series of studies done to examine the effects of naturalistic social disruption on structural plasticity and behavior in adult rats. Our results provide novel mechanistic evidence that social disruption shapes behavior in an adaptive way by reducing adult neurogenesis in the hippocampus. First, we developed an ethologically relevant model of social instability by forming stable dominance hierarchies in a visible burrow system and then switching dominant rats between hierarchies, a manipulation that increased aggression. Next, we examined the brains of rats subjected to social disruption and compared them to those living in a stable hierarchy and to those living in standard laboratory cages. We found that social disruption dramatically reduced the number of neural stem cells, as well as the number of new neurons, in the hippocampus regardless of social position. Instead of producing the predicted deleterious consequences of social stress, like impaired cognition and increased anxiety, we found no change in cognition and reduced anxiety-like behavior in rats from a disrupted hierarchy. We also found that socially disrupted rats did not show impairments in the ability to detect novelty in a social setting, but they did show a preference for familiar, as opposed to novel, conspecifics. Taken together, this behavioral profile suggests a potential ¿stress inoculation¿ or resilience, as opposed to the emergence of pathology. Next, we used two approaches to investigate whether these behavioral effects were causally linked to the reduction in adult neurogenesis in the hippocampus. We used oxytocin to stimulate adult neurogenesis just after social disruption occurred and found that this manipulation prevented the preference for familiar conspecifics. Then we used transgenic conditional neurogenesis knockout (GFAP-TK) rats to reduce adult neurogenesis in rats without social disruption experience and found that these rats preferred familiar rats, similar to what we observed in social disrupted wild-types. The mechanisms by which new neurons influence social preference remain to be determined. Advisors/Committee Members: Gould, Elizabeth (advisor).

Subjects/Keywords: Adult neurogenesis; Hippocampus; Resilience; Social disruption

11 more images…

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Opendak, M. (2015). Social instability, hippocampal plasticity and resilience . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp013197xp36d

Chicago Manual of Style (16^th Edition):

Opendak, Maya. “Social instability, hippocampal plasticity and resilience .” 2015. Doctoral Dissertation, Princeton University. Accessed January 16, 2021. http://arks.princeton.edu/ark:/88435/dsp013197xp36d.

MLA Handbook (7^th Edition):

Opendak, Maya. “Social instability, hippocampal plasticity and resilience .” 2015. Web. 16 Jan 2021.

Vancouver:

Opendak M. Social instability, hippocampal plasticity and resilience . [Internet] [Doctoral dissertation]. Princeton University; 2015. [cited 2021 Jan 16]. Available from: http://arks.princeton.edu/ark:/88435/dsp013197xp36d.

Council of Science Editors:

Opendak M. Social instability, hippocampal plasticity and resilience . [Doctoral Dissertation]. Princeton University; 2015. Available from: http://arks.princeton.edu/ark:/88435/dsp013197xp36d

7. Caponiti, Julia M. GENE EXPRESSION IN MOTOR NEURONS WITH DIFFERENTIAL SUSCEPTIBILITY TO AMYOTROPHIC LATERAL SCLEROSIS (ALS) .

Degree: PhD, 2012, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp014f16c286j

► Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes widespread motor neuron degeneration in the brain and spinal cord and eventually leads to… (more)

▼ Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes widespread motor neuron degeneration in the brain and spinal cord and eventually leads to paralysis and death. Although most motor neurons are vulnerable to ALS, a few groups survive until late stages of the disease. The oculomotor nucleus (OMN), which innervates the eye muscles, and Onuf's nucleus, which innervates the muscles of the penis and anal sphincter, are both resistant to degeneration in ALS (Mannen et al., 1977; Alexianu et al., 1994). The rodent homologue of Onuf's nucleus is the spinal nucleus of the bulbocavernosus (SNB). Like ALS patients, ALS transgenic rodent models exhibit less cell death in the OMN and SNB than in other motor neuron populations (Nimchinsky et al., 2000; Hamson et al., 2002). My dissertation research is aimed at exploring differences in gene expression between motor neurons that are resistant to degeneration and those that are vulnerable to degeneration with the ultimate goal of identifying genes that can be further explored for their ability to protect against ALS-induced death. To examine gene expression in motor neurons with differential susceptibility to ALS, I used microarray analysis on the two resistant motor neuron populations (OMN, SNB) compared to two vulnerable motor neuron populations - the trigeminal nucleus (TGN), which innervates face and mouth muscles, and the retrodorsolateral nucleus (RDLN), which innervates the foot muscles. Multiple genes with differential expression between resistant and vulnerable motor neuron populations were identified. After stringent statistical analyses, there were 47 genes with higher expression in the resistant motor neurons and 42 genes with higher expression in the vulnerable motor neurons. Two of these genes were selected for further investigation based on their known functions. Brain expressed, X-linked 1 (Bex1) had greater expression in the resistant motor neuron populations, and ribosomal protein s6 kinase, polypeptide 5 (Rps6ka5 or Msk1) had greater expression in the vulnerable motor neurons. I verified the expression patterns of these genes using confocal optical intensity analyses of immunolabeled tissue and western blots to ensure that the differences in gene expression translated into differences in protein expression. BEX1 and MSK1 were then investigated at a presymptomatic time point in a rodent model of ALS (mutant SOD1G93A transgenic rats) using confocal optical intensity analyses. BEX1 had significantly greater expression in the resistant motor neurons than the vulnerable motor neurons in both the transgenics and the wildtypes, with no significant differences between the two groups of animals. It is possible that BEX1 would be further upregulated after the onset of symptoms, or that it is a protective mechanism that is not modified by the disease process itself. MSK1 had significantly greater expression in the vulnerable motor neurons than the resistant motor neurons, with no difference between groups… Advisors/Committee Members: Gould, Elizabeth (advisor).

Subjects/Keywords: amyotrophic lateral sclerosis; BEX1; motor neuron; MSK1; neurodegenerative disease

…procedures were approved by Princeton University IACUC and conformed to guidelines for the care and… …Agilent Feature Extraction, and the Princeton University Microarray database (PUMAdb)…

11 more images…

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Caponiti, J. M. (2012). GENE EXPRESSION IN MOTOR NEURONS WITH DIFFERENTIAL SUSCEPTIBILITY TO AMYOTROPHIC LATERAL SCLEROSIS (ALS) . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp014f16c286j

Chicago Manual of Style (16^th Edition):

Caponiti, Julia M. “GENE EXPRESSION IN MOTOR NEURONS WITH DIFFERENTIAL SUSCEPTIBILITY TO AMYOTROPHIC LATERAL SCLEROSIS (ALS) .” 2012. Doctoral Dissertation, Princeton University. Accessed January 16, 2021. http://arks.princeton.edu/ark:/88435/dsp014f16c286j.

MLA Handbook (7^th Edition):

Caponiti, Julia M. “GENE EXPRESSION IN MOTOR NEURONS WITH DIFFERENTIAL SUSCEPTIBILITY TO AMYOTROPHIC LATERAL SCLEROSIS (ALS) .” 2012. Web. 16 Jan 2021.

Vancouver:

Caponiti JM. GENE EXPRESSION IN MOTOR NEURONS WITH DIFFERENTIAL SUSCEPTIBILITY TO AMYOTROPHIC LATERAL SCLEROSIS (ALS) . [Internet] [Doctoral dissertation]. Princeton University; 2012. [cited 2021 Jan 16]. Available from: http://arks.princeton.edu/ark:/88435/dsp014f16c286j.

Council of Science Editors:

Caponiti JM. GENE EXPRESSION IN MOTOR NEURONS WITH DIFFERENTIAL SUSCEPTIBILITY TO AMYOTROPHIC LATERAL SCLEROSIS (ALS) . [Doctoral Dissertation]. Princeton University; 2012. Available from: http://arks.princeton.edu/ark:/88435/dsp014f16c286j

8. Bocarsly, Miriam E. The influence of obesity on structure, biochemistry and function of brain regions involved in cognition .

Degree: PhD, 2013, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp015t34sj614

► Obesity is a major public health problem, affecting more than one-third of the U.S. population. Several studies suggest deficits in cognition in obese people and… (more)

▼ Obesity is a major public health problem, affecting more than one-third of the U.S. population. Several studies suggest deficits in cognition in obese people and several neuroimaging studies indicate reduced volume of certain brain regions, including the hippocampus and prefrontal cortex. These brain regions are important for cognition and anxiety regulation, and thus structural change in them may contribute to alterations in cognition and mood reported in overweight people. No studies have investigated the effects of weight gain on brain structure and function at a level of analysis that would permit identification of cellular mechanisms, which could lead to future treatment options. This dissertation uses a rat model of diet-induced obesity (DIO) to explore behavioral, structural and biochemical changes in three brain regions important in cognition: the medial prefrontal cortex (mPFC), perirhinal cortex (PRC), and hippocampus (HIP). Obese rats performed poorly on cognitive tasks specific to the mPFC and PRC, but not the HIP, compared to normal weight controls. In order to begin to characterize the behavioral differences observed, the influence of obesity on brain volume, dendritic architecture and spine density, as well as on associated pre- and post-synaptic markers in the mPFC, PRC and HIP were determined. Deficits in mPFC and PRC-related tasks were accompanied by decreased dendritic spine density and decreased pre- and post-synaptic markers in the mPFC and PRC. Finally, to identify potential mechanisms that might be driving these results, hormones that have previously been linked to changes in brain structure, and/or metabolism and obesity, were surveyed. While there was no difference in testosterone, glucose or insulin levels between groups, leptin was increased in the DIO model, providing a potential mechanism leading to changes in neurological structure and function. Further, obese rats had decreased peripheral corticosterone levels, a condition previously linked to decreased dendritic architecture, suggesting another potential involved mechanism. The DIO animal model of obesity has allowed us to look into the cellular changes that underlie alterations in brain structure and function, and provided us with foundational research needed to identify mechanisms for future intervention. Advisors/Committee Members: Gould, Elizabeth (advisor).

Subjects/Keywords: cognition; dendritic architecture; diet-induced obesity; medial prefrontal cortex; obesity; rat

…protocols were approved by the Princeton University IACUC and follow the NIH Guide for the Care…

11 more images…

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Bocarsly, M. E. (2013). The influence of obesity on structure, biochemistry and function of brain regions involved in cognition . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp015t34sj614

Chicago Manual of Style (16^th Edition):

Bocarsly, Miriam E. “The influence of obesity on structure, biochemistry and function of brain regions involved in cognition .” 2013. Doctoral Dissertation, Princeton University. Accessed January 16, 2021. http://arks.princeton.edu/ark:/88435/dsp015t34sj614.

MLA Handbook (7^th Edition):

Bocarsly, Miriam E. “The influence of obesity on structure, biochemistry and function of brain regions involved in cognition .” 2013. Web. 16 Jan 2021.

Vancouver:

Bocarsly ME. The influence of obesity on structure, biochemistry and function of brain regions involved in cognition . [Internet] [Doctoral dissertation]. Princeton University; 2013. [cited 2021 Jan 16]. Available from: http://arks.princeton.edu/ark:/88435/dsp015t34sj614.

Council of Science Editors:

Bocarsly ME. The influence of obesity on structure, biochemistry and function of brain regions involved in cognition . [Doctoral Dissertation]. Princeton University; 2013. Available from: http://arks.princeton.edu/ark:/88435/dsp015t34sj614

9. Chen, Yu-Wei. Neurochemical control of ethanol consumption: Differential systems for initiation and prolongation of drinking behavior .

Degree: PhD, 2012, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp018623hx77w

► Recent studies of alcoholism have demonstrated that specific patterns of drinking differentially impact the development of certain medical conditions. Notably, clinical medications for alcoholism differentially… (more)

▼ Recent studies of alcoholism have demonstrated that specific patterns of drinking differentially impact the development of certain medical conditions. Notably, clinical medications for alcoholism differentially affect distinct components of this disorder, preventing relapse, related to effects on the initiation or frequency of drinking episodes, or reducing overall consumption, reflecting effects on the intensity or duration of drinking. This underscores the importance of investigating neural mechanisms that underlie specific patterns of alcohol drinking. Preclinical studies suggest that the perifornical lateral hypothalamus (PF/LH) and its local peptide orexin (OX), through positive interaction with peptide systems in the paraventricular nucleus (PVN), have an important function in stimulating alcohol consumption and may also affect specific patterns of alcohol drinking. The research described in this dissertation investigates this possibility using Sprague-Dawley rats trained to voluntarily drink ethanol. Chapter 2 tests the hypothesis that OX in the PF/LH stimulates ethanol consumption through its specific effect on the initiation of ethanol drinking. This is in contrast to the PVN peptides, galanin (GAL) and enkephalin (ENK), which primarily determine the size and duration of the drinking response and can also be stimulated by OX in the PVN. To more fully understand the function of OX in controlling ethanol drinking, the next three chapters examine PF/LH neurotransmitter systems that are stimulated by ethanol consumption and may, in turn, modulate the PF/LH peptides. Chapter 3 focuses on the glutamatergic system and tests the hypothesis that glutamatergic inputs act as an initiation signal to stimulate OX and induce ethanol drinking. Chapter 4 investigates the role of DA and the idea that it has receptor-specific actions, acting at the dopamine 1 receptor to enhance OX and stimulate ethanol drinking and at the dopamine 2 receptor to suppress OX and terminate the drinking process. Chapter 5 then investigates opioid signals, which in the PF/LH may inhibit drinking as well as the OX system. Collectively, these experiments provide new information regarding OX and its function in controlling patterns of ethanol drinking, elucidating the neural basis of alcohol drinking patterns and offering insight into how casual alcohol drinking may eventually become a chronic, debilitating disorder. Advisors/Committee Members: Gould, Elizabeth (advisor), Leibowitz, Sarah (advisor).

…the Princeton University Institutional Animal Care, and conformed to the National Institutes…

10 more images…

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Chen, Y. (2012). Neurochemical control of ethanol consumption: Differential systems for initiation and prolongation of drinking behavior . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp018623hx77w

Chicago Manual of Style (16^th Edition):

Chen, Yu-Wei. “Neurochemical control of ethanol consumption: Differential systems for initiation and prolongation of drinking behavior .” 2012. Doctoral Dissertation, Princeton University. Accessed January 16, 2021. http://arks.princeton.edu/ark:/88435/dsp018623hx77w.

MLA Handbook (7^th Edition):

Chen, Yu-Wei. “Neurochemical control of ethanol consumption: Differential systems for initiation and prolongation of drinking behavior .” 2012. Web. 16 Jan 2021.

Vancouver:

Chen Y. Neurochemical control of ethanol consumption: Differential systems for initiation and prolongation of drinking behavior . [Internet] [Doctoral dissertation]. Princeton University; 2012. [cited 2021 Jan 16]. Available from: http://arks.princeton.edu/ark:/88435/dsp018623hx77w.

Council of Science Editors:

Chen Y. Neurochemical control of ethanol consumption: Differential systems for initiation and prolongation of drinking behavior . [Doctoral Dissertation]. Princeton University; 2012. Available from: http://arks.princeton.edu/ark:/88435/dsp018623hx77w

10. Brockett, Adam Thomas. Astrocytes regulate cognitive flexibility and neuronal oscillations by releasing S100b .

Degree: PhD, 2017, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp01tx31qm30b

► Astrocytes are the most numerous cell in the human brain yet their role in behavior and brain functioning has remained incompletely explored. The goal of… (more)

Subjects/Keywords: Astrocytes; Cognition; Cognitive Flexibility; Glia; Medial Prefrontal Cortex; Neuronal Oscillations

…approved by the Princeton University IACUC (protocol # 1852, approved June 2014) and… …occurred between 0900 and 1400. All studies were approved by the Princeton University IACUC (…

4 more images…

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Brockett, A. T. (2017). Astrocytes regulate cognitive flexibility and neuronal oscillations by releasing S100b . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp01tx31qm30b

Chicago Manual of Style (16^th Edition):

Brockett, Adam Thomas. “Astrocytes regulate cognitive flexibility and neuronal oscillations by releasing S100b .” 2017. Doctoral Dissertation, Princeton University. Accessed January 16, 2021. http://arks.princeton.edu/ark:/88435/dsp01tx31qm30b.

MLA Handbook (7^th Edition):

Brockett, Adam Thomas. “Astrocytes regulate cognitive flexibility and neuronal oscillations by releasing S100b .” 2017. Web. 16 Jan 2021.

Vancouver:

Brockett AT. Astrocytes regulate cognitive flexibility and neuronal oscillations by releasing S100b . [Internet] [Doctoral dissertation]. Princeton University; 2017. [cited 2021 Jan 16]. Available from: http://arks.princeton.edu/ark:/88435/dsp01tx31qm30b.

Council of Science Editors:

Brockett AT. Astrocytes regulate cognitive flexibility and neuronal oscillations by releasing S100b . [Doctoral Dissertation]. Princeton University; 2017. Available from: http://arks.princeton.edu/ark:/88435/dsp01tx31qm30b

		in
And / Or
		in
And / Or
		in
And / Or
		in

Open Access Theses and Dissertations