Regulation of ventral hippocampal system function

腹侧海马系统功能的调节

基本信息

批准号：
9304377
负责人：
Daniel Lodge
金额：
$ 35.75万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9304377
关键词：
Address Affect Amphetamines Antipsychotic Agents Autopsy Behavior Behavioral Cognitive Cognitive deficits Data Development Dimensions Disease Dopamine ErbB4 gene Estrus Female Functional disorder Funding Ganglia Genetic Transcription Hippocampus (Brain)Hyperactive behavior Immunohistochemistry Interneuron function Interneurons Lead Locomotion Malnutrition Measures Medial Midbrain structure Mus NRG1 gene Neurobehavioral Manifestations Neurobiology Neurons Parvalbumins Pathogenesis Pathologic Pathology Patients Pharmaceutical Preparations Physiological Poly I-C Population Psychotic Disorders Rattus Regulation Reporting Research Domain Criteria Reversal Learning Risk Factors Rodent Model Role Schizophrenia Social Interaction Somatostatin Stem cell transplant Symptoms System Therapeutic Transplantation brain pathway cognitive function dopamine system dopaminergic neuron embryonic stem cell fetal flexibility human imaging imaging study inhibitory neuron knock-down migration neurophysiology novel therapeutic intervention prenatal public health relevance response small hairpin RNA social attention symptom cluster transcriptome sequencing transmission process

项目摘要

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.

描述（由适用提供）：精神分裂症是一种毁灭性的精神病疾病，影响多达1％的美国人口。在上一个资金期间，我们报告说，海马中间神经元功能的损失概括了患者的高多巴胺能状态的基础。此外，我们最近提供了最早的报告之一，描述了中间神经元移植（源自胎儿内侧神经节隆起）的可行性，作为治疗精神分裂症的新型热方法。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能状态。在本提案中，我们现在将解决不仅严重使人衰弱的负面和认知缺陷问题，而且不受抗精神病药的良好治疗。走向这个最后，我们计划检查两个单独的间神经元种群，即白蛋白和生长抑素，在离散但相互联系的神经元系统（VHIPP和MPFC）中的作用，可能是这些符号的基础。更广泛地说，这个概念对于理解研究领域标准项目（RDOC）中详细介绍的行为和神经生物学措施的维度至关重要。综上所述，提出的研究将提供对离散间神经元种群在精神分裂症病理生理学中的作用的理解，并将研究干细胞移植作为该疾病的潜在治疗方法。