Regulation of ventral hippocampal system function

腹侧海马系统功能的调节

• 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
• 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

 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，影响高达1%的美国人口。在之前的资助期间，我们报道了海马中间神经元功能的丧失，重现了被认为是患者精神病基础的多巴胺能亢进状态。此外，我们最近提供了第一个报告描述的可行性interneuron移植（来自胎儿内侧神经节隆起）作为一种新的治疗方法治疗精神分裂症。在这些最初的研究中，我们主要关注被认为是精神病基础的多巴胺能亢进状态。在本提案中，我们现在将解决不仅严重衰弱，而且抗精神病药物治疗效果不佳的负面和认知缺陷问题。为实现这一 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，在离散但相互连接的神经元系统（vHipp和mPFC）中的作用，这些神经元系统可能是精神分裂症症状群的基础。更广泛地说，这个概念是理解行为和神经生物学测量的核心，如研究领域标准项目（RDoC）中所详述的。两者合计，提出的研究将提供一个离散的中间神经元群体在精神分裂症的病理生理学的作用的理解，并将检查干细胞移植作为一种潜在的治疗这种疾病的效用。