Cerebellum and Mental Disorders

小脑和精神障碍

• 批准号: 10378581
• 负责人: Kamran Khodakhah
• 金额: $ 53.96万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378581
• 关键词: Acute; Affect; Agreement; Anatomy; Axon; Behavior; Behavioral; Brain; Brain imaging; Brain region; Calcium; Cells; Cerebellar Nuclei; Cerebellum; Characteristics; Cognitive; Color; Complement; Data; Defect; Development; Disease; Dizygotic Twins; Electrophysiology (science); Functional disorder; General Population; Genetic; Goals; Head; Hypothalamic structure; Image; Impairment; In Vitro; Link; Mental disorders; Monozygotic twins; Motor; Movement; Mus; Mutation; Neurons; Nucleus Accumbens; Odds Ratio; Oxytocin; Pathologic; Pathway interactions; Perception; Physiological; Physiology; Play; Prefrontal Cortex; Process; Purkinje Cells; Reporting; Research; Rewards; Risk Factors; Rodent; Rodent Model; Role; Schizophrenia; Slice; Social Behavior; Structure; Techniques; Testing; Time; Vasopressins; Ventral Tegmental Area; Wild Type Mouse; addiction; autism spectrum disorder; autistic; awake; base; behavioral study; cognitive function; experimental study; imaging study; in vivo; insight; mouse model; optogenetics; paraventricular nucleus; repetitive behavior; social; social influence

Abstract The cerebellum has been implicated in a number of mental health disorders such as autism spectrum disorder (ASD), schizophrenia, and addiction. However, how it contributes to these disorders is not understood. In this proposal we explore whether the cerebellum sends direct excitatory projections to the ventral tegmental area (VTA), one of the brain regions that processes and encodes reward, and to the hypothalamus, a region implicated in social behavior. Using a combination of anatomical, functional (electrophysiology combined with selective optogenetic activation of cerebellar pathways), and behavioral studies we test the hypothesis that direct cerebellar projections to these two brain structures may be the substrate through which the cerebellum influences social behavior under physiological and pathological conditions. Defects in cerebellar modulation of the VTA and hypothalamus may explain, at least in part, how the cerebellum might contribute to disorders such as ASD and schizophrenia. Thus, accomplishment of the goals set would not only advance our understanding of the non-motor functions of the cerebellum, but may provide clues regarding the pathophysiology of a number of mental disorders.

抽象的 小脑与自闭症谱系等多种心理健康疾病有关 疾病（ASD），精神分裂症和成瘾。但是，它如何对这些疾病做出贡献不是 理解。在此提案中，我们探讨了小脑是否将直接的兴奋性预测发送给 腹侧盖区域（VTA）是处理和编码奖励的大脑区域之一， 下丘脑，与社会行为有关的地区。结合解剖学功能 （电生理学与小脑途径的选择性光遗传学激活相结合）和 行为研究我们检验了将小脑投影直接介绍到这两个大脑结构的假设 可能是小脑在生理和 病理状况。 VTA和下丘脑的小脑调节中的缺陷可以解释 至少在某种程度上，小脑如何导致ASD和精神分裂症等疾病。因此， 实现目标设定不仅会提高我们对非运动功能的理解 小脑，但可能会提供有关许多精神生理学的线索 疾病。