Cerebellum and Mental Disorders

小脑和精神障碍

• 批准号: 9906767
• 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/9906767
• 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

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 小脑与许多精神健康障碍有关，例如自闭症谱系障碍 障碍（ASD）、精神分裂症和成瘾症。然而，它如何导致这些疾病尚不清楚 明白了。在这个提案中，我们探讨小脑是否向大脑发送直接兴奋性投射 腹侧被盖区（VTA），处理和编码奖励的大脑区域之一， 下丘脑，一个与社会行为有关的区域。结合解剖学、功能学 （电生理学与小脑通路的选择性光遗传学激活相结合），以及 行为研究我们测试了将小脑投射到这两个大脑结构的假设 可能是小脑在生理和心理条件下影响社会行为的基质 病理状况。 VTA 和下丘脑的小脑调节缺陷可以解释， 至少部分地，小脑如何导致自闭症谱系障碍和精神分裂症等疾病。因此， 实现既定目标不仅会增进我们对非运动功能的理解 的小脑，但可能提供有关许多精神疾病的病理生理学的线索 失调。