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Mapping mesocortical contributions to estrous-dependent learning processes

绘制中皮质对发情依赖性学习过程的贡献

基本信息

批准号：
9807686
负责人：
REBECCA M SHANSKY
金额：
$ 23.27万
依托单位：
NORTHEASTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9807686
关键词：
3-Dimensional Adult Agonist Amygdaloid structure Animal Model Area Attention Biology Brain Cognitive Complex Conditioned Reflex Cues Data Disease Dopamine Dopamine D1 Receptor Estrogens Estrous Cycle Estrus Exposure to Extinction (Psychology)Female Fright Hormones Immunohistochemistry Investigation Label Lead Learning Light Maps Medial Mediating Memory Neurobiology Neurons Neurophysiology - biologic function Outcome Ovarian hormone Pathway interactions Patients Persons Phase Post-Traumatic Stress Disorders Prefrontal Cortex Prevalence Process Proestrus Psychological reinforcement Rattus Recovery Rodent Role Signal Transduction Structure Synapses System Techniques Testing Therapeutic Time Tracer Translating Trauma Tyrosine 3-Monooxygenase United States Ventral Tegmental Area Viral Woman Work base common treatment conditioned fear dopaminergic neuron effective therapy human model improved insight intersectionality learning extinction male men neural circuit new therapeutic target novel reconstruction recruit reduce symptoms relating to nervous system sex success tool traumatic event

项目摘要

Summary Women are twice as likely as men to develop Post-Traumatic Stress Disorder (PTSD) after a trauma, but the neurobiological basis for this discrepancy is poorly understood. While there is a great deal of evidence that trauma itself can impact the male and female brain in discrete ways, less attention has been paid to the potential for PTSD treatments to work in a sex-dependent manner. A better understanding of the mechanisms that specifically mediate PTSD recovery in women could lead to improved therapeutics and a higher success rate for symptom reduction. In particular, the neural processes by which ovarian hormones modulate extinction learning represent a promising area of focus. Here, we will investigate the influence of circulating estrogen on the structure and function of neural circuitry connecting the ventral tegmental area (VTA), infralimbic area (IL) of the medial prefrontal cortex (mPFC), and basolateral area of the amygdala (BLA) in rats. We propose a system by which high estrogen states facilitate IL-BLA connectivity and enhanced extinction retention through upstream modulation of VTA-IL DA release during extinction learning. To test this hypothesis, we will use a combination of neuroanatomical tracers, intersectional viral techniques, and 3D reconstructions, thereby defining fear extinction-associated neural activity and plasticity across the estrous cycle. This work will result in a multi-synaptic map of extinction circuitry in the female brain, potentially identifying novel mechanisms by which estrogen can modulate learning processes.

总结