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（由申请人提供）：精神分裂症是一种毁灭性的精神疾病，影响着多达 1% 的美国人口。在上一个资助期间，我们报告说，海马中间神经元功能的丧失，概括了被认为是患者精神病基础的多巴胺能亢进状态。此外，我们最近提供了首批报告之一，描述了中间神经元移植（源自胎儿内侧神经节隆起）作为一种新的治疗方法的可行性在这些初步研究中，我们主要关注被认为是精神病背后的多巴胺能亢进状态，现在我们将解决消极和认知缺陷的问题，这些问题不仅会严重削弱患者的能力，而且抗精神病药物也无法很好地治疗这些问题。对此进行药物治疗。最后，我们计划研究两个独立的中间神经元群体，即小清蛋白和生长抑素，在离散但相互关联的神经系统（vHipp 和 mPFC）中的作用，这可能是精神分裂症这些症状群的基础。更广泛地说，这个概念对于理解维度至关重要。研究领域标准项目 (RDoC) 中详细介绍了行为和神经生物学测量方法。总而言之，所提出的研究将提供对离散中间神经元群体在神经元中的作用的理解。精神分裂症的病理生理学，并将研究干细胞移植作为这种疾病的潜在治疗方法的效用。