Dendritic Integration and Cerebellar Synaptic Plasticity

树突整合和小脑突触可塑性

• 批准号: 7371175
• 负责人: Samuel Sheng-Hung Wang
• 金额: $ 32.79万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7371175
• 关键词: Action Potentials; Animals; Autistic Disorder; Automobile Driving; Axon; Behavior; Brain; Calcium; Calcium Signaling; Cerebellar cortex structure; Cerebellum; Chromosome Pairing; Cognitive; Complex; Computer information processing; Defect; Dendrites; Dendritic Spines; Depth; Detection; Development; Electrophysiology (science); Event; Fiber; Fire - disasters; Goals; Image; In Vitro; Inferior; Inherited Spinocerebellar Degenerations; Knowledge; Laboratories; Learning; Life; Link; Long-Term Depression; Microscopy; Modeling; Monitor; Motor; Movement Disorders; Multiphoton Fluorescence Microscopy; Neurons; Neurotransmitters; Olives - dietary; Optics; Output; Pathway interactions; Pattern; Play; Process; Purkinje Cells; Relative (related person); Research Project Grants; Resolution; Role; Second Messenger Systems; Sensory; Sensory Process; Shapes; Signal Transduction; Site; Slice; Stimulus; Stream; Structure; Synapses; Synaptic plasticity; System; Techniques; Testing; Thinking; Time; Trauma; Vertebral column; Vertebrates; base; brain tissue; density; fluorescence imaging; granule cell; in vivo; insight; interest; millisecond; mossy fiber; motor learning; photolysis; receptor; relating to nervous system; research study; response; second messenger; technique development; two-photon; voltage

DESCRIPTION (provided by applicant): The cerebellum, a brain structure found in all vertebrates, is thought to guide motor learning based on sensory inputs. The overall goal of this project is to understand, at a fundamental level, how sensory information is integrated by Purkinje neurons. Purkinje neurons are of interest because they are the point of convergence for the two main input streams to the cerebellum, the mossy fiber/parallel fiber pathway and the inferior olive/climbing fiber pathway. In addition, Purkinje neurons are the cerebellum's sole output and are thought to play a key role in modulating motor and cognitive activity. Two-photon microscopy, which allows optical sectioning and imaging deep in brain tissue, will enable the observation of dendritic processing in brain slices, and observation of many neurons at once in living animals. Patterned photolysis of caged neurotransmitters and second messengers will allow spatially complex dendritic activity to be manipulated with millisecond resolution. This proposal will test the following three ideas. (1) Complex patterns of granule cell inputs are integrated by Purkinje cells according to two kinds of rules, a dendritic integration rule for local changes and a somatic rule for determining firing output. (2) Purkinje cells have single synapse-level mechanisms for detecting the timing of granule cell activity relative to two kinds of instructive input: climbing fiber activity and local dendritic depolarization. (3) Purkinje cells are activated in vivo in subdendritic and multicellular patterns to generate signals that drive output firing and synaptic plasticity. Taken together, these three ideas contribute to a model in which patterns of activity in granule cells undergo plasticity, and can themselves drive plasticity, to shape Purkinje cell output.

描述（由申请人提供）：小脑是所有脊椎动物中都存在的一种大脑结构，被认为可以指导基于感觉输入的运动学习。该项目的总体目标是从根本上了解浦肯野神经元如何整合感觉信息。浦肯野神经元之所以令人感兴趣，是因为它们是小脑的两个主要输入流（苔藓纤维/平行纤维通路和下橄榄/攀爬纤维通路）的汇聚点。此外，浦肯野神经元是小脑的唯一输出，被认为在调节运动和认知活动中发挥着关键作用。双光子显微镜可以对脑组织深处进行光学切片和成像，从而能够观察脑切片中的树突状处理，并同时观察活体动物中的许多神经元。笼中神经递质和第二信使的图案化光解将允许以毫秒分辨率操纵空间复杂的树突活动。该提案将测试以下三个想法。 (1) 颗粒细胞输入的复杂模式由浦肯野细胞根据两种规则进行整合，即用于局部变化的树突整合规则和用于确定发射输出的体细胞规则。 (2)浦肯野细胞具有单突触水平机制，用于检测颗粒细胞活动相对于两种指导输入的时间：攀爬纤维活动和局部树突去极化。 (3) 浦肯野细胞在体内以树突下和多细胞模式被激活，产生驱动输出放电和突触可塑性的信号。综上所述，这三个想法构成了一个模型，在该模型中，颗粒细胞的活动模式具有可塑性，并且本身可以驱动可塑性，从而塑造浦肯野细胞的输出。