Sensorimotor integration in mammalian cerebellum

哺乳动物小脑的感觉运动整合

• 批准号: 8610514
• 负责人: Abigail L Person
• 金额: $ 33.58万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8610514
• 关键词: Acute; Area; Automobile Driving; Axon; Behavior; Brain; Bypass; Cell Nucleus; Cells; Cerebellar Ataxia; Cerebellar Diseases; Cerebellar Nuclei; Cerebellum; Cytoplasmic Granules; Data; Excitatory Synapse; Fiber; Genetic; Glutamates; Goals; Golgi Apparatus; Interneurons; Intervention; Label; Mammals; Measurement; Mediating; Medical; Modeling; Motor; Motor Cortex; Motor output; Movement; Movement Disorders; Mus; Neural Pathways; Neurons; Neurotransmitters; Nuclear; Pathway interactions; Patients; Phenotype; Physiological; Pontine structure; Preparation; Property; Reporter; Role; Sensory; Sensory Process; Shapes; Signal Transduction; Slice; Synapses; System; Tactile; Testing; Theoretical model; Therapeutic; Time; Tracer; Transgenic Mice; Update; base; cell type; cellular targeting; granule cell; in vivo; innovation; insight; motor control; neglect; nervous system disorder; neural circuit; neurotensin type 1 receptor; next generation; optogenetics; postsynaptic; presynaptic; public health relevance; receptor; response; sensory feedback; theories

Project Summary/Abstract: Corollary discharge (CD), or a copy of efferent motor commands, is integral to numerous models cerebellar motor control. CD is hypothesized to provide a reference signal to update internal models of current motor state and modify reafferent sensory input that is predicted by the motor command, placing it at the center of sensorimotor integration. Our understanding of the specific anatomical and physiological circuitry of CD in the mammalian cerebellum is limited, however, owing to anatomical constraints that complicate studying motor cortex-derived CD signals. Our approach bypasses these obstacles by focusing on a neglected pathway consisting of collaterals from the premotor cerebellar nuclei to the cerebellar granule cell layer. This experimentally accessible "nucleocortical" pathway has all of the hallmarks of a CD pathway in that it consists of motor output neurons that also project to sensory receptive areas. We propose to investigate the organization and function of this pathway in mice as a means to understand the mechanisms and role of corollary discharge in sensory processing in mammalian cerebellum. To test the hypothesis that CD both updates internal models and suppresses sensory reafference, we will use anatomical and physiological approaches to examine whether the nucleocortical pathway forms excitatory synapses onto feedforward excitatory granule neurons and feedforward inhibitory Golgi neurons. This arrangement would provide a mechanism for the proposed roles of CD in motor control. To further test the prediction that CD can modify sensory reafference, we will examine whether sensory responses in the granule cell layer are sensitive to concurrent activation or inactivation of the nucleocortical pathway. We expect that the motor CD pathway from the cerebellar nuclei contacts granule cells and Golgi cells, converges with other sensory cerebellar afferents, and modifies sensory processing by the granule cell layer. These studies will aid in our long term goal of understanding the circuit mechanisms of feedforward motor control in mammals, which is critical for precise movement and hypothesized to be impaired in movement disorders that involve the cerebellum.

项目总结/文摘: