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Principal Investigator: Courtney Anne Bouchet
Organization: COLORADO STATE UNIVERSITY
Fiscal Year: 2024
Award: $77,227
Funding agency: National Heart Lung and Blood Institute
Project Summary
Cardiovascular diseases are the leading cause of death globally and pathologies are exacerbated by
chronic stress. Stress-cardiovascular comorbidities are more prevalent in females, however, the
neurobiological mechanisms linking stress to cardiovascular outcomes are not well understood and could
inform underlying cardiovascular susceptibility and resilience. The prefrontal cortex and hypothalamus are key
regulators of stress and cardiovascular output; therefore, this proposal will test the hypothesis that cortical-
hypothalamic neural circuitry mediates the sexually divergent cardiovascular consequences of chronic stress.
Chronic psychosocial stress increases the incidence of cardiovascular diseases. The prefrontal cortex
(PFC) is critical for stress appraisal, and both mood disorders and chronic stress are associated with altered
PFC function. Recently, the sponsor’s lab reported that optogenetically activating the predominantly
glutamatergic projection neurons from the rat infralimbic PFC (IL) produces sexually divergent effects on the
stress response. However, the IL does not directly innervate neuroendocrine or preganglionic sympathetic
neurons to mediate these effects; therefore, intermediate neurocircuitry must be involved in translating sex-
specific cortical processing into sex-specific cardiovascular outcomes.
The posterior hypothalamus (PH) is a major target of IL projection neurons and IL-PH projection
neurons are stress-activated, however, neuroanatomical studies examining IL-PH circuitry have been
performed exclusively in males. Pharmacological inactivation of the PH in vivo restrains acute stress
responses while pharmacologically activating the PH exacerbates acute stress responses. PH activity also
regulates cardiovascular function: pharmacologically activating the PH increases blood pressure and heart rate
and pharmacological inactivation of the PH robustly blocks stress-induced increases in heart rate. The
proposed experiments hypothesize that the PH is an intermediate synapse for sexually divergent outcomes
and that stress-induced plasticity in this region mediates cardiovascular consequences of chronic stress.
To test this hypothesis, I will learn viral-mediated circuit- and cell-type-specific slice
electrophysiology to investigate synaptic plasticity within the IL-PH circuit after chronic variable stress in
males and females. Additionally, I will learn pulse wave velocity and pressure myography to investigate
vascular stiffness and reactivity in vivo and ex vivo, respectively, to determine the necessity of the IL-PH circuit
for the detrimental consequences of chronic stress on vascular function.
I have assembled a mentorship team with accomplished neurophysiologists and cardiovascular
biologists to ensure the technical and career development training necessary for this project and, ultimately,
starting my independent laboratory. These mentors will be critical for navigating my postdoctoral fellowship and
preparing to run an independent research program studying unique dimensions of cardiovascular resilience.
Terms: <4-Aminobutanoic Acid><4-Aminobutyric Acid><4-amino-butanoic acid><Affective Disorders><Aminalon><Aminalone><Anatomic Sites><Anatomic structures><Anatomy><Animals><Architecture><Blood Pressure><Blood Vessels><Brodmann's area><CNS plasticity><Cardiac Chronotropism><Cardiovascular><Cardiovascular Body System><Cardiovascular Diseases><Cardiovascular Organ System><Cardiovascular Pathology><Cardiovascular Physiology><Cardiovascular system><Cause of Death><Cell Communication and Signaling><Cell Signaling><Chronic><Chronic stress><Common Rat Strains><Data><Deep Brain Stimulation><Differences between sexes><Differs between sexes><Dimensions><Electrophysiology><Electrophysiology (science)><Endothelium><Engineering / Architecture><Ensure><Fellowship><Female><GABA><Gene Transcription><Genetic Transcription><Glutamates><Heart Rate><Heart Vascular><Human><Hypothalamic structure><Hypothalamus><Impairment><Incidence><Intracellular Communication and Signaling><L-Glutamate><Laboratories><Learning><Link><Mediating><Mental Depression><Mentors><Mentorship><Microvascular Dysfunction><Modern Man><Mood Disorders><Myography><Nerve Cells><Nerve Unit><Neural Cell><Neuranatomies><Neuranatomy><Neuroanatomies><Neuroanatomy><Neurocyte><Neuroendocrine><Neuroendocrine System><Neuronal Plasticity><Neurons><Neurophysiology / Electrophysiology><Neurosecretory Systems><Outcome><Output><Paraventricular Hypothalamic Nucleus><Pathology><Pharmacological Study><Pharmacology Study><Physiologic><Physiologic pulse><Physiological><Postdoc><Postdoctoral Fellow><Posterior Hypothalamic Region><Posterior Hypothalamus><Predictive Factor><Predisposition><Prefrontal Cortex><Psychosocial Stress><Pulse><RNA Expression><Rat><Rats Mammals><Rattus><Reporting><Research><Research Associate><Resistance><Risk><Role><Running><Sex Differences><Sexual differences><Signal Transduction><Signal Transduction Systems><Signaling><Slice><Stress><Susceptibility><Synapses><Synaptic><Synaptic plasticity><Tachycardia><Testing><Training><Transcription><Transgenic Organisms><Translating><Vascular Diseases><Vascular Disorder><Viral><Woman><Women's prevalence><Work><acute stress><arterial stiffening><arterial stiffness><arteriole><artery stiffening><artery stiffness><biological adaptation to stress><biological signal transduction><blood pressure elevation><blood vessel disorder><cardiovascular disorder><cardiovascular effects><cardiovascular function><cardiovascular health><cardiovascular risk><cardiovascular risk factor><career><career development><cell type><central nervous system plasticity><circulatory system><co-morbid><co-morbidity><comorbidity><depression><electrophysiological><elevated blood pressure><excitatory neuron><experiment><experimental research><experimental study><experiments><female prevalence><gamma-Aminobutyric Acid><glutamatergic><hypothalamic><in vivo><increase in blood pressure><increased blood pressure><inhibitory neuron><knock-down><knockdown><knowledge base><male><microvascular complications><microvascular disease><neural circuit><neural circuitry><neural plasticity><neurobiological mechanism><neurocircuitry><neuronal><neuroplastic><neuroplasticity><optogenetics><paraventricular nucleus><pharmacologic><post-doc><post-doctoral><post-doctoral trainee><postsynaptic><pressure><presynaptic><prevalence among females><prevalence among women><prevalence in females><prevalence in women><prevalent among females><prevalent among women><prevalent in females><prevalent in women><prevent><preventing><programs><reaction; crisis><research associates><resilience><resilient><resistant><response><restraint><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><skills><small vessel disease><social role><stress response><stress; reaction><synapse><synaptic circuit><synaptic circuitry><transgenic><vascular><vascular dysfunction><vasculopathy><γ-Aminobutyric Acid>