Prenatal stress and the development of inhibitory neurons in the forebrain

描述（由申请人提供）：本申请提供了一个综合临床儿童和成人精神病学、发育神经科学动物模型和应激神经生物学的职业发展奖。目前的目标是创建一个研究产前压力的神经生物学影响的发育机制的项目，重点是抑制性神经元。长期目标是有助于理解导致儿童和成人严重精神疾病的早期发育事件，精神分裂症和图雷特综合征等疾病的病理生理学，以及干预措施如何改变早期发育变化。该候选人获得了美国国立卫生研究院资助的神经科学博士学位，在过去的5年里，他一直在耶鲁儿童研究中心（YCSC）和精神病学部门接受临床和研究精神病学的综合培训。该奖项将为她在YCSC发育神经生物学实验室继续进行综合研究提供关键支持，并在理解儿童和成人精神疾病的框架内过渡到基础发育神经科学的独立职业生涯。本课题将利用动物模型研究产前应激对中枢神经系统结构和功能的广泛、持续影响的机制。gaba能系统将是研究计划的重点，因为患有精神分裂症和其他与人类产前压力相关的行为障碍的患者具有异常的gaba能神经元群。史蒂文斯博士将在这个奖项的支持下完成第一阶段的研究计划，即产前应激对抑制性神经元的解剖学影响，以及她在博士后工作中发展起来的技能。然后，她将继续评估产前应激在胚胎时期和成年发育期间影响gaba能种群的分子机制。抑制性神经元系统的功能将通过行为和电生理措施进行检查。这项实验工作还包括该候选人的职业发展计划，以获得独立从事基础神经科学研究的必要技能，可以研究有关精神疾病神经发育的重要问题。候选人已经招募了一组优秀的导师和顾问，他们将指导研究计划的设计，实验的执行和结果的分析。在职业发展方面，该导师和顾问团队将继续支持候选人在YCSC开发与精神疾病神经发育相关的独立实验室项目，并通过课程、密集研讨会和国家会议进行分子、行为和电生理技术方面的额外培训。

DESCRIPTION (provided by applicant: This application presents a career development award that integrates clinical child and adult psychiatry, animal models of developmental neuroscience, and stress neurobiology. The immediate goal is to create a program investigating the developmental mechanisms of the neurobiological effects of prenatal stress, focused on inhibitory neurons. The long term objective is to contribute to the understanding of early developmental events that contribute to severe childhood and adult psychiatric illness, the pathophysiology that underlies disorders such as schizophrenia and Tourette syndrome, and how interventions can modify early developmental changes. The candidate completed a Ph.D. in neuroscience with individual NIH funding and has now been involved in comprehensive training in clinical and research psychiatry for the past 5 years at the Yale Child Study Center (YCSC) and Department of Psychiatry. This award will provide critical support for the continuation of her integrated research in the YCSC Developmental Neurobiology Laboratory and the transition to an independent career in basic developmental neuroscience within the framework of understanding child and adult psychiatric illness. In the research proposal, an animal model of prenatal stress will be used to study the mechanisms of widespread, persistent effects on CNS structure and function. GABAergic systems will be the focus of the research plan, as patients with schizophrenia and other behavioral disorders linked to prenatal stress in humans have abnormal GABAergic neuron populations. Dr. Stevens will complete the first stage of the research plan on the anatomical effects of prenatal stress on inhibitory neurons with the support of this award and the skills she has developed in her postdoctoral work. She will then go on to make assessments of molecular mechanisms of prenatal stress affecting GABAergic populations both during the embryonic time period and during adult development. Functioning of inhibitory neuronal systems will be examined with behavioral and electrophysiological measures. This experimental work also comprises the career development plan for this candidate to obtain the necessary skills for an independent career in basic neuroscience research that can investigate important questions about the neurodevelopment of mental illness. The candidate has recruited an outstanding group of mentors and advisors that will guide the research plan in design, performance of experiments, and analysis of results. For career development, this mentor and advisor team will continue to support the candidate as she develops an independent laboratory program at the YCSC relevant to the neurodevelopment of mental illness and as she pursues additional training in molecular, behavioral, and electrophysiological techniques through coursework, intensive workshops and national conferences.