Characterizing sensorimotor gaiting dysfunction in mouse models of schizophrenia

精神分裂症小鼠模型感觉运动步态功能障碍的特征

• 批准号: 8582022
• 负责人: Kafui Dzirasa
• 金额: $ 22.87万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8582022
• 关键词: Amygdaloid structure; Area; Auditory Evoked Potentials; Behavioral; Biological; Biological Neural Networks; Brain; Complex; Corpus striatum structure; Data; Decision Making; Development; Disease; Dopamine; Emotional; Functional disorder; Genes; Genetic; Glutamates; Goals; Hallucinogens; Human; Implant; Interneurons; Intervention; Measures; Mediating; Microelectrodes; Midbrain structure; Modeling; Mus; Neurons; Outcome; Patients; Phencyclidine; Physiologic pulse; Play; Predisposition; Prefrontal Cortex; Process; Relative (related person); Research; Risk; Rodent; Role; Schizophrenia; Signal Transduction; Stimulus; Techniques; Testing; Thalamic structure; Variant; Ventral Tegmental Area; Work; base; endophenotype; in vivo; insight; mouse model; neural circuit; neurophysiology; neuropsychiatry; novel; pre-clinical; prepulse inhibition; public health relevance; repaired; response; sensory gating

DESCRIPTION (provided by applicant): Multiple studies have identified sensorimotor gating deficits in patients with schizophrenia, their first degree "unaffected" relatives, and in pharmacological and genetic mouse models of schizophrenia. These deficits in sensorimotor gating may serve as a hallmark endophenotype of the disorder. Here we propose to directly quantify the neurophysiological mechanisms that correspond with sensory gating in mice by implanting arrays of microelectrodes across 7 distinct brain areas comprising mesolimbic, mesocortical, and cortical-striatal-thalamic microcircuits and performing neurophysiological recordings as mice perform a classic sensorimotor gating task. We will then quantify the effect of the psychotomimetic agent PCP and the schizophrenia risk gene DISC1 on these circuit mechanisms. We believe that the insights derived from the current proposal into the distributed circuits that underlie normal sensorimotor gating, and the mechanisms whereby genetic and pharmacological manipulations disrupt these circuits, will provide a detailed network-level understanding of the neurophysiological alterations that may contribute to schizophrenia.

描述（由申请人提供）：多项研究已经确定了精神分裂症患者的感觉运动门控缺陷，其第一级“不受影响”的亲属以及精神分裂症的药理学和遗传小鼠模型中。感官门控的这些缺陷可能是该疾病的标志性内表型。在这里，我们建议通过在7个不同的大脑区域中植入微型，中皮层和皮质 - 纹状体 - 纹状体 - 丘脑 - 丘脑 - 丘脑 - thalamic的微环形和执行神经噬菌学记录的神经生理学记录的群体，直接量化与小鼠感觉门控相对应的神经生理机制。然后，我们将量化精神病剂PCP和精神分裂症风险基因盘对这些电路机制的影响。我们认为，从当前的提案中得出的洞察力源于正常感觉运动门控的分布式电路，以及遗传和药理学操纵破坏这些电路的机制，将提供对可能促成精神分裂症的神经生理变化的详细网络级别的理解。