Dissecting the Role of Long Range Prefrontal Circuits in Early-life Stress Induced Susceptibility

联系PD/PI：Atsak，Piray 项目摘要 我的职业目标是成为一名神经回路水平机制的专家， 发育压力和压力个体差异的潜在传递 反应和灵敏度。我计划领导一个研究实验室， 早期生活压力（ELS）的机制和个体差异的出现， 成人应激反应ELS会造成抑郁症和焦虑症的长期风险， 尤其是在成年期面临压力事件之后。然而，人们对 ELS如何在神经回路水平上产生持续的变化， 对压力的敏感性。这种详细的电路解剖不可能 在人类中进行，因此通过使用最近建立的早期生命的两次打击模型， 和成年小鼠的压力，其中在特定的出生后窗口期间的压力增加了 成年压力诱发抑郁样行为的可能性。在K 01项目中， 在RFMH和哥伦比亚大学的Rene Hen博士的指导下， 长距离前额叶回路在ELS诱导的成人压力易感性中的作用。我 将联合收割机与先进的方法， 作为多部位电生理记录和交叉途径， 特定的化学遗传学操作。这些研究代表了许多第一次在 发展/系统神经科学领域：1）第一个测试的作用，一些长期的- 范围前额叶皮层相关回路（前额叶-杏仁核，腹侧 海马）活动和沟通的压力敏感性; 2）第一次解剖 ELS引起的成年人神经回路活动和通信变化 应激反应; 3）第一个研究ELS对应激敏感性的影响， 女性潜在的神经回路; 4）第一个将联合收割机发展压力与 同时多点记录和交叉方法， 操纵这些研究代表了一个重大的职业变化和研究 这个K 01奖将为我提供指导和额外的培训 这将为我实现职业目标和建立独立的研究做好准备。 该计划旨在调查ELS导致终身的神经回路 易患抑郁症和精神疾病。 项目总结/摘要

Contact PD/PI: Atsak, Piray Project Summary My career goal is to become an expert on the circuit level mechanisms of neural transmission underlying developmental stress and individual differences in stress response and sensitivity. I plan to lead a research lab studying the neurophysiological mechanisms of early-life stress (ELS) and the emergence of individual differences in adult stress response. ELS creates long-term risk to depression and anxiety disorders, particularly after facing stressful events during adulthood. However, little is known about how ELS produces sustained changes at the neural circuitry level that increase sensitivity to stress later in life. This kind of detailed circuit dissection cannot be performed in humans, thus by using a recently established two-hit model of early-life and adult stress in mice in which stress during a specific postnatal window increases the likelihood of adulthood stress to induce depressive-like behaviors. With this K01 grant and under the mentorship of Dr. Rene Hen at RFMH and Columbia University, I will test the role of long-range prefrontal circuits in the ELS-induced susceptibility to adult stress. I will combine an established two-hit mouse model of stress with advanced methods such as multi-site electrophysiological recordings and intersectional approaches for pathway specific chemogenetic manipulations. These studies represent a number of firsts in the developmental/systems neuroscience field: 1) the first to test the role of some of the long- range prefrontal cortex associated circuits (prefrontal-accumbens, amygdala, ventral hippocampus) activity and communication in stress susceptibility; 2) the first to dissect neural circuit activity and communication underlying the ELS-induced changes in adult stress response; 3) the first to investigate the impact of ELS in stress-susceptibility and underlying neural circuits in females; 4) the first to combine developmental stress with simultaneous multi-site recordings and intersectional approaches for pathway specific manipulations. These studies represent a significant career change and research redirection for me. This K01 award will afford me the mentorship and additional training that will prepare me to achieve my career goals and establish an independent research program geared towards investigating the neural circuits of which ELS leads to lifelong susceptibility to depression and psychiatric disorders. Project Summary/Abstract