Dendritic Integration and Cerebellar Synaptic Plasticity

树突整合和小脑突触可塑性

• 批准号: 6832829
• 负责人: Samuel Sheng-Hung Wang
• 金额: $ 33.77万
• 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 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6832829
• 关键词: Dendritic; Integration; Cerebellar; Synaptic; Plasticity

EXCEED THE SPACE PROVIDED. The cerebellum, a brain structure found in all vertebrates, is thought to serve many sensory-motor coordinating functions. In particular, decades of evidence suggest that the cerebellum guides motor learning based on sensory inputs. One laboratory example of motor learning thought to involve the cerebellum is a task in which a conditional stimulus, such as an audible tone, is associated with an unconditional stimulus, such as an airpuff delivered to the eye. Eventually the subject learns to blink in response to the tone played alone. For learning to occur the tone must come first, suggesting that the cerebellum can detect the order in which events occur. Under synaptic activity conditions thought to match the order-dependence of this task, one molecular event is elevation of calcium, a widely used signaling ion, inside cerebellar Purkinje neurons. Calcium, in turn, induces long-term depression, a form of synaptic plasticity at parallel fiber synapses to the Purkinje neuron that may underlie motor learning. This proposal will test the following ideas: (1) Conditional stimulus information coming in through parallel fiber synapses is encoded by the chemical messenger inositol-l,4,5-trisphosphate (IP3). (2) Unconditional stimulus information coming through the climbing fiber synapse is encoded by a small amount of priming calcium that enters during the action potential. (3) Synapses in the cerebellum generate large amounts of calcium release from internal stores when both IP3 and priming calcium are generated. (4) The order-dependence seen in calcium signaling is caused by dynamics in IP3, calcium, and calcium release mechanisms. This hypothesis will be tested using multiphoton laser scanning fluorescence microscopy, a technique that allows calcium signals to be measured at single synapses; and light-sensitive "caged" compounds, which can be used to control biochemical events in cerebellar Purkinje neurons. These experiments will provide crucial basic knowledge regarding the molecular events that occur on a time scale of milliseconds to seconds during synaptic plasticity and motor learning, and may eventually help in understanding defects in cerebellar function. PERFORMANCE SITE ========================================Section End===========================================

超出所提供的空间。 小脑是所有脊椎动物中都存在的一种大脑结构，被认为具有许多感觉运动协调功能。特别是，数十年的证据表明小脑根据感觉输入指导运动学习。一个被认为涉及小脑的运动学习的实验室例子是一项任务，其中条件刺激（例如可听音调）与无条件刺激（例如向眼睛吹气）相关联。最终，对象学会了眨眼来响应单独播放的音调。为了学习发生，音调必须首先出现，这表明小脑可以检测事件发生的顺序。在被认为与该任务的顺序依赖性相匹配的突触活动条件下，一个分子事件是小脑浦肯野神经元内钙的升高，钙是一种广泛使用的信号离子。反过来，钙会引起长期抑郁，这是浦肯野神经元平行纤维突触处突触可塑性的一种形式，可能是运动学习的基础。该提案将测试以下想法：（1）通过平行纤维突触传入的条件刺激信息由化学信使肌醇-1,4,5-三磷酸（IP3）编码。 (2) 通过攀爬纤维突触的无条件刺激信息由动作电位期间进入的少量启动钙编码。 (3) 当产生 IP3 和启动钙时，小脑中的突触会从内部储存中释放大量钙。 (4) 钙信号传导中的顺序依赖性是由 IP3、钙和钙释放机制的动态引起的。这一假设将使用多光子激光扫描荧光显微镜进行测试，该技术允许在单个突触处测量钙信号；以及光敏“笼中”化合物，可用于控制小脑浦肯野神经元的生化事件。这些实验将提供有关突触可塑性和运动学习过程中以毫秒到秒的时间尺度发生的分子事件的重要基础知识，并最终可能有助于理解小脑功能的缺陷。表演网站==========================================部分结束====== =======================================