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Plasticity in deep cerebellar nuclei as a function of classical conditioning

小脑深部核团的可塑性作为经典条件反射的函数

基本信息

批准号：
7844830
负责人：
BERNARD G. SCHREURS
金额：
$ 19.88万
依托单位：
WEST VIRGINIA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-15 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7844830
关键词：
Address Adult Age Animals Anterior Behavior Behavior Control Behavioral Behavioral Model Biological Blinking Brain Cell Nucleus Cells Cerebellar Nuclei Cerebellar cortex structure Cerebellum Data Development Eyelid structure Failure Gene Expression Goals Grant Hand Health Human In Vitro Injection of therapeutic agent Intervention Label Learning Lesion Lobe Lobule Mediating Membrane Memory Modeling Motor Neurons Oryctolagus cuniculus Pathogenesis Play Positioning Attribute Preparation Property Purkinje Cells Rattus Research Role Series Slice Solutions Synapses Synaptic Membranes Synaptic plasticity Techniques Testing Time Tracer Viral Work base classical conditioning conditioning experience eyelid conditioning innovation insight novel strategies prevent public health relevance pup relating to nervous system research study response success

项目摘要

DESCRIPTION (provided by applicant): To help determine the biological basis of learning and memory, our research seeks to understand how plasticity in the cerebellum mediates eyeblink conditioning. To pursue this goal, we have recorded in vitro learning-specific synaptic and membrane changes in Purkinje cells of the rabbit cerebellar cortex following eyelid conditioning. There are two limitations to this approach. First, a number of different cerebellar lobules are involved in eyelid conditioning. Second, it is not possible to confirm whether cells in which changes are detected were involved in the behavior. There is now a potential solution to these problems. First, all cerebellar lobules project to deep cerebellar nuclei and there is growing evidence that changes in neural activity, synapse number and gene expression occur within the anterior interpositus nucleus as a result of eyeblink conditioning. Second, there are retrograde neuronal track tracing techniques able to identify deep cerebellar neurons involved in the eyeblink. However, although these cells can be visualized, there is a dense perineuronal net surrounding adult deep cerebellar nuclei that prevents recording from these cells. To overcome all of these limitations, we are developing a rat pup cerebellar slice preparation in which we can visualize and record from eyeblink-related neurons in the anterior interpositus following injection of a fluorescent retrograde tracer into the eyelid. With this preparation in hand, we will address two specific aims: (1) identify and characterize anterior interpositus neurons involved in the rat eyeblink; and (2) determine the changes in synaptic and intrinsic membrane properties of identified anterior interpositus neurons that occur as a result of eyeblink conditioning. This work is important because of the impact it will have on understanding the synaptic and intrinsic membrane changes underlying learning and memory in a well-understood behavioral model. The proposed work is innovative because it develops a slice preparation that for the first time provides data on the role of identified neurons involved in learning and memory. It combines a novel approach - visually identifiable response-related neurons in the anterior interpositus nucleus with advanced in vitro electrophysiological recording techniques in a well-understood model of learning and memory - rat eyeblink conditioning. PUBLIC HEALTH RELEVANCE: The evidence is clear that damage to the deep cerebellar nuclei in animals and humans has a major impact on both motor and non-motor forms of learning and memory. Consequently, examining changes in the synaptic and intrinsic membrane properties of cells in the cerebellar nuclei as a function of eyeblink conditioning in rats may provide insights into the biological mechanisms of learning and memory. By identifying these changes, the proposed work has the potential to help understand the pathogenesis of failures in learning and memory and to develop intervention strategies for those failures.

描述（由申请人提供）：为了帮助确定学习和记忆的生物学基础，我们的研究旨在了解小脑的可塑性如何介导眨眼条件反射。为了实现这一目标，我们记录了在体外学习特定的突触和膜的变化，兔小脑皮质浦肯野细胞眼睑条件反射。这种方法有两个局限性。首先，许多不同的小脑小叶参与眼睑调节。其次，无法确认检测到变化的细胞是否参与了行为。现在有一个潜在的解决这些问题的办法。首先，所有的小脑小叶都投射到小脑深层核，越来越多的证据表明，眨眼条件反射导致前间位核内神经活动、突触数量和基因表达发生变化。第二，有逆行神经追踪技术能够识别涉及眨眼的小脑深部神经元。然而，尽管这些细胞可以被可视化，但成年人小脑深核周围有一个致密的神经元束膜网，阻止了这些细胞的记录。为了克服所有这些局限性，我们正在开发一种大鼠幼鼠小脑切片制备，在这种切片中，我们可以将荧光逆行示踪剂注射到眼睑中后，在前间位中观察和记录与眨眼相关的神经元。有了这个准备工作，我们将解决两个具体的目标：（1）确定和表征参与大鼠眨眼的前间位神经元;（2）确定作为眨眼条件反射的结果发生的已确定的前间位神经元的突触和内在膜特性的变化。这项工作很重要，因为它将对理解突触和内在膜变化的影响，这些变化是在一个很好理解的行为模型中学习和记忆的基础。这项工作具有创新性，因为它开发了一种切片制备方法，首次提供了有关参与学习和记忆的已识别神经元作用的数据。它结合了一种新的方法-视觉上可识别的反应相关的神经元在前间位核与先进的体外电生理记录技术在一个很好的理解模型的学习和记忆-大鼠眨眼条件反射。公共卫生相关性：证据清楚地表明，动物和人类小脑深部核团的损伤对运动和非运动形式的学习和记忆都有重大影响。因此，研究大鼠小脑核中细胞的突触和内在膜特性的变化作为眨眼条件反射的函数，可能会为学习和记忆的生物学机制提供见解。通过识别这些变化，拟议的工作有可能帮助理解学习和记忆失败的发病机制，并为这些失败制定干预策略。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ontogeny of trace eyeblink conditioning to shock-shock pairings in the rat pup.

幼鼠中微量眨眼条件反射对电击-电击配对的个体发育。

DOI：
10.1037/a0031298
发表时间：
2013
期刊：
Behavioral neuroscience
影响因子：
1.9
作者：
Schreurs,BernardG;Burhans,LaurenB;Smith-Bell,CarrieA;Mrowka,SylwiaW;Wang,Desheng
通讯作者：
Wang,Desheng