ShEEP Request for Optogenetics Equipment

项目摘要/摘要 这项提议所要求的集成系统是体内光遗传学，它结合了光遗传学 具有行为工具的技术。这项创新技术使调查人员能够控制 通过光遗传操作来研究其下游对多种神经元的影响 生物过程。光遗传学对神经科学的研究产生了深远的影响。光遗传 结合特定细胞型转基因动物的用光改变神经元放电和功能的技术 LINES越来越多地被用作研究神经障碍和精神疾病的新工具，包括 阿尔茨海默病(AD)、创伤性脑损伤(TBI)、药物成瘾和抑郁症。在布朗克斯，詹姆斯·J。 彼得斯医学中心，科学家小组正专注于神经学和心理学的研究 在退伍军人群体中有重要影响的疾病。朱利奥·玛丽亚·帕西内蒂博士目前 正在开发新的研究，探索睡眠剥夺(SD)的作用，这是退伍军人群体中的一个主要问题， 尤其是在患有创伤后应激障碍(PTSD)的受试者中，认知功能改变。所请求的 设备将使帕西内蒂博士能够使用新的光遗传技术来研究如何选择化合物 可能调节SD介导的记忆巩固缺陷，在对记忆重要的敏感脑区 功能，如海马体结构。同样，蔡东明博士将利用体内光基因测试来 研究与运动蛋白相关的记忆功能的变化，如动力素和突触素 AD的发病机制。王军博士正在与帕西内蒂博士合作开发一项新的项目 抑郁和焦虑，与中棘突触可塑性适应不良有关 伏核(NAC)的神经元(MSN)。NAC包含GABA能投射的两种亚型 神经元：含多巴胺D1和D2受体的MSN。拟议中的光遗传技术将使博士。 Wang和Pasinetti在应激诱导中研究Nac D1和D2神经元的选择性贡献 抑郁表型。此外，通过对d1和d2 MSN的选择性光遗传刺激，研究人员 我可以进一步研究新的干预措施如何机械地影响这两个人 NAC中神经元的亚群，并提供对抑郁/焦虑的弹性。格雷戈里·埃尔德医生的 项目是在轻度(M)脑创伤的大鼠模型中研究与爆炸相关的脑损伤的神经生物学。一直以来 研究表明，杏仁核和包括前额叶皮质和海马体在内的相关区域是大脑 创伤性创伤后应激障碍的研究进展。这些结构与人类的恐惧反应有关 动物也是如此。拟议的光遗传技术将提供新的手段来阐明 杏仁核在调节与其他结构有关的动机反应、恐惧和记忆方面发挥着重要作用。法特梅博士 HagHighi与Elder博士合作，正在研究可能导致脑外伤的表观遗传机制-- 诱导性神经紊乱。综上所述，在体光遗传工具的获取应用 与JJPVA可用的神经行为核心相结合，将允许该应用程序的支持者 阐明杏仁核、海马体、新皮质和大脑皮质的分子机制 其他神经回路对病理条件下的认知损害提供新的治疗方法 预防和治疗与退行性变相关的生理性和相互关联的退行性疾病的目标 任务，包括SD引起的认知障碍、情绪障碍、AD和脑外伤。总而言之， 体内光遗传系统的获得将为现有的 行为设施，并可适应神经科学中广泛的问题。我们 我坚信，布朗克斯退伍军人健康中心的所有研究人员都可以从这项新技术中受益。

PROJECT SUMMARY/ABSTRACT The integrated system requested for this proposal is in vivo optogenetics, which combines optogenetic technology with behavioral tools. This innovative technology allows the investigators to control the activity of specific neurons through optogenetic manipulation to study their downstream influence on a variety of biological processes. Optogenetics has made a profound impact on the research of neuroscience. Optogenetic technologies to alter neuronal firing and function with light, combined with cell-type specific transgenic animal lines, is increasingly used as a novel tool to study neurological disorders and psychiatric diseases, including Alzheimer's disease (AD), traumatic brain injury (TBI), drug addiction and depression. At the Bronx James J. Peters Medical Center, groups of scientists are focusing on investigations of neurological and psychological disorders that have important implications in the Veteran population. Dr. Giulio Maria Pasinetti is currently developing new studies exploring the role of sleep deprivation (SD), a major issue in the Veteran population, in particular in subjects with post-traumatic stress disorder (PTSD), in altered cognitive function. The requested equipment will enable Dr. Pasinetti to use novel optogenetic technology to investigate how select compounds may modulate SD-mediated memory consolidation deficits in susceptible brain regions important for memory function, such as the hippocampal formation. Similarly, Dr. Dongming Cai will use in vivo optogenetic testing to investigate changes in memory function associated with motor proteins, such as dynamin and synaptojanin, in the pathogenesis of AD. Dr. Jun Wang is developing a new program in collaboration with Dr. Pasinetti on depression and anxiety, which are associated with maladaptation of synaptic plasticity in the medium spiny neurons (MSNs) in the nucleus accumbens (NAc). The NAc contains two subtypes of GABAergic projection neurons: dopamine D1 and D2 receptor-containing MSNs. The proposed optogenetic techniques will allow Drs. Wang and Pasinetti to address the selective contributions of NAc D1 and D2 neurons in stress-induced depression phenotypes. Moreover, by selective optogenetic stimulation of D1 and D2 MSNs, the investigators can further examine how mechanistically the novel intervention may differentially influence these two subpopulations of neurons in the NAc and provide resilience against depression/anxiety. Dr. Gregory Elder's project is to investigate the neurobiology of blast-related brain injury in a rat model of mild (m)TBI. It has been shown that the amygdala and related regions including the prefrontal cortex and hippocampus are keys in the development of TBI-induced PTSD. These structures are implicated in mediating fear responses in humans and animals as well. The proposed optogenetic techniques will provide novel means to elucidate the role of the amygdala in regulating motivational responses, fear and memory in relation to other structures. Dr. Fatemeh Haghighi, in collaboration with Dr. Elder, is investigating the epigenetic mechanisms that may contribute to TBI- induced neurological disorders. Collectively, the application for the acquirement of in vivo optogenetic tools combined with the available neurobehavioral core at the JJPVA will allow the proponents of this application to clarify the molecular mechanisms to identify the contributions of the amygdala, hippocampus, neocortex and other neural circuits to cognitive impairments under pathological conditions and provide novel therapeutic targets for preventing and treating physiological and interconnected degenerative conditions relevant to the VA mission, including SD-induced cognitive impairment, mood disorders, AD and TBI. In summary, the acquirement of the in vivo optogenetic system will provide a fundamental molecular tool to the existing behavioral facility and can be adapted to an extensive landscape of questions within neuroscience. We strongly believe that all investigators at the Bronx VA Health Center can benefit from this novel technology.