Cerebellar Output Circuits

小脑输出电路

基本信息

批准号：
10158334
负责人：
SASCHA DU LAC
金额：
$ 38.52万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10158334
关键词：
Affect Affective Amygdaloid structure Anatomy Area Arousal Attention Axon Behavior Behavioral Biological Markers Brain Stem Brain region Cells Cerebellar Nuclei Cerebellar vermis structure Cerebellum Cognitive Cognitive deficits Depressed mood Diagnosis Disease Electroencephalography Emotional Emotions Evaluation Eye Movements Functional disorder Genes Goals Head Movements Hippocampus (Brain)Impaired cognition Impairment Label Lead Link Location Measures Medial Mediating Mental Depression Mental disorders Methods Modernization Molecular Mood Disorders Moods Motor Mus Neurons Nucleus fastigii Output Pattern Pharmacology Physiological Pontine structure Posture Prefrontal Cortex Presynaptic Terminals Purkinje Cells Pyramidal Cells Reporter Reporting Research Role Saccades Schizophrenia Stroke Structure Syndrome System Testing Thalamic Nuclei Thalamic structure Therapeutic Effect Update affective disturbance autism spectrum disorder cell type cholinergic cingulate cortex cognitive ability cognitive function emotion regulation executive function experimental study improved insight motor control neural circuit neuromechanism novel therapeutic intervention optogenetics public health relevance response sustained attention tumor

项目摘要

Proposal Summary DESCRIPTION (provided by applicant): Impairments in prefrontal cortical function are associated with many psychiatric disorders, including schizophrenia, mood disorders, and autism. Surprisingly, the vermis - a small part of the cerebellum best known for its role in posture and eye movements - has been strongly implicated in each of these disorders. Deficits in executive control of saccadic eye movements are used as biomarkers for schizophrenia, autism, and depression, consistent with a dual role of the vermis in regulating both motoric and prefrontal cortical function. However, neither the neural circuit substrates that link the cerebellar vermis with the prefrontal cortex nor the functional impact of these connections are understood. The central hypothesis of this proposal is that the affective and cognitive functions of the cerebellar vermis are mediated by a specific class of cerebellar nucleus neuron that makes circuit connections with the reticular activating system, a critical regulator of arousal and cortical state, as well as with neurons of the medial thalamus that are essential for prefrontal cortical function. The proposed experiments will test this hypothesis with a combination of modern anatomical, physiological, pharmacological, optogenetic, and behavioral strategies. Deficits in cerebellar engagement with the reticular activating system and the thalamus could account for mood dysregulation and cognitive deficits common to several psychiatric disorders. Accomplishing the aims of the proposed research will result in unprecedented cell type specific information about the long-range circuit connections that link the cerebellar vermis with the prefrontal cortex that account for cerebellar modulation of affective and cognitive function. This research will thus generate new insights into the mechanisms that mediate currently unexplained efficacy of transcranial stimulation of the cerebellum in improving cognitive and mood dysfunction in psychiatric disorders.

提案摘要描述（申请人提供）：前额叶皮质功能的损害是与许多精神疾病有关，包括精神分裂症，情绪障碍，和自闭症。令人惊讶的是，vermis-小脑的一小部分以其闻名在姿势和眼睛运动中的作用 - 在这些中都有很大的影响疾病。萨斯卡德眼动的执行控制缺陷被用作精神分裂症，自闭症和抑郁症的生物标志物，与调节摩托车和额叶皮质功能的vermis。但是，都不是将小脑vermis与前额叶皮层联系起来的神经回路底物这些连接的功能影响已被理解。中心假设建议是小脑vermis的情感和认知功能是由特定类型的小脑核神经元介导的，该神经元建立电路连接与网状激活系统（唤醒和皮质状态的关键调节剂）一起以及与前额叶皮质必不可少的内侧丘脑神经元功能。提出的实验将通过结合现代解剖学，生理，药理，光学遗传学和行为策略。小脑与网状激活系统的缺陷和丘脑可以解释几个常见的情绪失调和认知缺陷精神疾病。完成拟议研究的目标将导致关于远程电路连接的前所未有的细胞类型特定信息那将小脑vermis与小脑的前额叶皮层联系起来情感和认知功能的调节。因此，这项研究将产生新的洞悉介导当前无法解释的经颅功效的机制刺激小脑在改善精神病学认知和情绪功能障碍方面疾病。