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.

概括创伤后，女性患有创伤后应激障碍（PTSD）的可能性是男性的两倍，但是这种差异的神经生物学基础知之甚少。虽然有很多证据表明创伤本身可以以离散的方式影响男性和女性大脑，对 PTSD治疗以性依赖性方式工作的潜力。更好地理解机制特别介导女性的PTSD恢复可能会导致治疗疗法的改善和更高的成功减轻症状的比率。特别是，卵巢激素调节灭绝的神经过程学习代表着一个有希望的重点领域。在这里，我们将研究循环雌激素对连接腹侧对盖区域（VTA），输液区域（IL）的神经回路的结构和功能大鼠杏仁核（BLA）的内侧前额叶皮层（MPFC）和基底外侧面积。我们提出了一个高雌激素状态促进IL-BLA连接性并通过灭绝学习过程中VTA-IL DA释放的上游调制。为了检验这一假设，我们将使用神经解剖示踪剂，交叉病毒技术和3D重建的组合，从而定义恐惧灭绝相关的神经活动和整个发情周期的可塑性。这项工作将导致女性大脑中灭绝电路的多突触图，有可能通过哪种雌激素可以调节学习过程。