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Molecular and Cellular Neuroscience

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Western University

Theses/Dissertations

Stress

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Examining The Role Of Chloride Homeostasis And Pge2 Signaling In The Neuroendocrine Stress Response To Inflammation, Samuel A. Mestern Aug 2021

Examining The Role Of Chloride Homeostasis And Pge2 Signaling In The Neuroendocrine Stress Response To Inflammation, Samuel A. Mestern

Electronic Thesis and Dissertation Repository

The brain senses inflammatory signals and drives the release of glucocorticoids (GCs) — potent immunosuppressants — via the activation of the hypothalamic-pituitary-adrenal (HPA) axis. This inflammation-induced HPA axis activation is largely mediated by prostaglandin E2 (PGE2), acting on two subtypes of the PGE2 receptor, EP1 and EP3. Recently, our group revealed EP3 signaling mechanisms that excite HPA axis regulatory neurons. This thesis sought to tease out the remaining EP1 signaling mechanisms. Considering that the excitability of HPA axis regulatory neurons is constrained by GABAA receptor-mediated synaptic inhibition that relies on low-level intracellular Cl-. We hypothesized that PGE2-EP1 …


Synaptic Correlates For Stress Sensitization, Julia Kj Sunstrum Aug 2018

Synaptic Correlates For Stress Sensitization, Julia Kj Sunstrum

Electronic Thesis and Dissertation Repository

The stress response is essential for survival, but it can be detrimental when persistently activated during chronic stress. Therefore, the magnitude of the stress response must be finely-tuned in order to be adaptive. Indeed, an animal’s stress response system normally undergoes habituation that decreases responses to a repeated, familiar stressor. Importantly, the same animal still responds normally, or even becomes sensitized, to an unfamiliar (novel) stressor. This indicates that chronic stress simultaneously induces two opposing types of plasticity, one that underlies habituated responses and another that drives sensitized responses. The activation of the hypothalamic-pituitary-adrenal (HPA) axis — a hallmark of …


Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla Oct 2016

Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla

Electronic Thesis and Dissertation Repository

Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR1 and 5-HT2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT2A/CRs. The first purpose of this thesis was …