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

• 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
• 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

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 女性在创伤后患创伤后应激障碍（PTSD）的可能性是男性的两倍，但 这种差异的神经生物学基础知之甚少。虽然有大量证据表明 创伤本身可以以不连续的方式影响男性和女性的大脑，但很少有人关注创伤本身。 PTSD治疗可能以性别依赖的方式起作用。更好地理解机制 在女性中特异性介导创伤后应激障碍的恢复可能会导致改善的治疗方法和更高的成功率， 症状缓解率。特别是卵巢激素调节灭绝的神经过程 学习是一个有希望的重点领域。在这里，我们将研究循环雌激素对 腹侧被盖区（VTA）、边缘下区（IL） 内侧前额叶皮质（mPFC）和杏仁核基底外侧区（BLA）。我们提出了一个 高雌激素状态促进IL-BLA连接和增强消光保留的系统， 消退学习过程中VTA-IL DA释放的上游调节。为了验证这个假设，我们将使用 结合神经解剖示踪剂，交叉病毒技术和3D重建，从而 定义恐惧防御相关的神经活动和可塑性在整个发情周期。这项工作将导致 女性大脑中灭绝电路的多突触图，可能通过以下方式识别新机制： 雌激素可以调节学习过程。