Regulation of ventral hippocampal system function

 描述(申请人提供)：精神分裂症是一种毁灭性的精神疾病，影响多达1%的美国人口。在之前的资助期间，我们报告了海马区中间神经元功能的丧失，重现了被认为是患者精神障碍基础的高多巴胺能状态。此外，我们最近提供了首批报告之一，描述了神经元间移植(来源于胎儿内侧神经节隆起)作为治疗精神分裂症的一种新的治疗方法的可行性。在这些最初的研究中，我们主要集中在被认为是精神病基础的高多巴胺状态。在目前的提案中，我们现在将解决负面和认知缺陷的问题，这些缺陷不仅使人严重虚弱，而且不能被抗精神病药物很好地治疗。朝向这个方向 最后，我们计划研究两个独立的中间神经元群体，即小白蛋白和生长抑素，在离散但相互连接的神经系统(vHipp和mPFC)中的作用，这些系统可能是精神分裂症这些症状群的基础。更广泛地说，这个概念对于理解研究领域标准项目(RDoC)中详细描述的行为和神经生物学测量的维度是核心的。综上所述，建议的研究将有助于了解离散的中间神经元群体在精神分裂症的病理生理学中的作用，并将检验干细胞移植作为这种疾病的潜在治疗方法的实用性。

 DESCRIPTION (provided by applicant): Schizophrenia is a devastating psychiatric condition that affects up to 1% of the US population. During the previous funding period, we reported that a loss of hippocampal interneuron function, recapitulates the hyperdopaminergic state thought to underlie psychosis in patients. In addition, we have recently provided one of the first reports describing the feasibility of interneuron transplants (derived from fetal medial ganglionic eminence) as a novel therapeutic approach for the treatment of schizophrenia. In these initial studies we focused primarily on the hyperdopaminergic state thought to underlie psychosis. In the present proposal, we will now address the issues of negative and cognitive deficits that are not only severely debilitating, but are not well treated by antipsychotic medications. Towards this end, we plan to examine the role of two separate interneuron populations, namely parvalbumin and somatostatin, in discrete but interconnected neuronal systems (the vHipp and mPFC) that likely underlie these symptoms clusters in schizophrenia. More broadly, this concept is central to understanding dimensions of behavior and neurobiological measures as detailed in the Research Domain Criteria project (RDoC). Taken together, the studies proposed will provide an understanding into the role of discrete interneuron populations in the pathophysiology of schizophrenia and will examine the utility of stem cell transplants as a potential treatment for this disease.