Cerebellar Circuitry and Plasticity in an Electric Fish

描述（由申请人提供）：小脑的神经回路似乎相对简单且定义明确，但该回路所执行的计算尚不清楚。此外，小脑中突触可塑性的形式已经被定义为可能负责运动学习，但关于这种可塑性的关键问题仍然没有答案。本研究的目的是通过对电鱼独特的小脑的研究来解决小脑回路和可塑性的基本问题。mormyrid小脑的两个特征使其非常适合解决这些问题：1)在mormyrid鱼中浦肯野细胞和小脑输出细胞（哺乳动物小脑核的细胞）彼此相邻，使得在这两种细胞类型之间的重要突触上进行整合和可塑性实验成为可能，而这在哺乳动物中无法进行。2)攀爬纤维终止区与浦肯野细胞平行纤维输入区在鼠体中有明显的分离，而在哺乳动物中则没有。这种分离有助于确定两个树突区域之间的内在差异，以及确定两个输入如何相互作用以产生突触可塑性。该项目有两个具体目的：1)确定电鱼浦肯野细胞和小脑输出细胞的基本突触和内在生理；2)确定电鱼平行纤维突触和浦肯野细胞突触的可塑性类型。主要方法将是在体外切片中进行全细胞贴片记录，并结合标记所记录的元素进行形态学鉴定。

DESCRIPTION (provided by applicant): The neuronal circuitry of the cerebellum appears to be relatively simple and well defined, but the computation performed by this circuitry is not understood. In addition, forms of synaptic plasticity have been defined in the cerebellum that may be responsible for motor learning, but critical questions regarding this plasticity are still unanswered. The objective of the proposed research is to address fundamental issues cerebella circuitry and plasticity through a study of the unique cerebellum of mormyrid electric fish. Two features of the mormyrid cerebellum make it well suited to address these issues: 1) Purkinje cells and cerebellar output cells (cells of the cerebellar nuclei in mammals) are adjacent to each other in mormyrid fish, making possible experiments on integration and plasticity at the important synapse between these two cell types that can not be done in mammals. 2) The regions of termination for climbing fiber and parallel fiber inputs on Purkinje cells are distinct and well separated in the mormyrid but not in the mammal. This separation facilitates the determination of intrinsic differences between the two dendritic regions and the determination of how the two inputs interact to generate synaptic plasticity. The project has two Specific Aims: 1) to determine the basic synaptic and intrinsic physiology of Purkinje and cerebellar output cells in mormyrid electric fish; and 2) to determine the types of plasticity at parallel fiber and Purkinje cell synapses in mormyrid electric fish. The primary method will be whole-cell patch recording in vitro slices, combined with labeling of recorded elements for morphological identification.