Cerebellar Output Circuits

小脑输出电路

• 批准号: 10397087
• 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
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397087
• 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; 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

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（由申请人提供）：前额皮质功能损伤是 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，蚓部——小脑的一小部分，以其功能而闻名。 在姿势和眼球运动中的作用 - 与这些中的每一个都密切相关 失调。对扫视眼球运动执行控制的缺陷被用作 精神分裂症、自闭症和抑郁症的生物标志物，与 蚓部调节运动和前额皮质功能。然而，无论是 连接小脑蚓部和前额皮质的神经回路基质 这些连接的功能影响是可以理解的。这个假设的中心假设 建议认为小脑蚓部的情感和认知功能是 由一类特定的小脑核神经元介导，该神经元进行电路连接 网状激活系统是唤醒和皮质状态的关键调节器， 以及对于前额皮质至关重要的内侧丘脑神经元 功能。所提出的实验将结合以下内容来检验这一假设 现代解剖学、生理学、药理学、光遗传学和行为学 策略。小脑与网状激活系统和神经网络的参与缺陷 丘脑可能是某些人常见的情绪失调和认知缺陷的原因 精神疾病。实现拟议研究的目标将导致 有关远程电路连接的前所未有的细胞类型特定信息 连接小脑蚓部和负责小脑的前额皮质 情感和认知功能的调节。因此，这项研究将产生新的 深入了解介导目前无法解释的经颅疗法功效的机制 刺激小脑改善精神病患者的认知和情绪功能障碍 失调。