ROLE OF CEREBELLAR CORTEX INTERNEURONS IN CEREBELLAR CORTEX FUNCTION

摘要 颗粒层是小脑皮质的输入层。它从多个大脑接收信息 通过长满苔藓的纤维。它通过颗粒细胞轴突将信息输出到分子层， 在那里它们接触其他中间神经元和浦肯野细胞(PC)[1-3]。我们对这一现象的深刻理解 小脑皮质颗粒层的解剖和生理学使这一结构成为理想的结构 研究局域网信号处理的模型系统。学习时的一个重要考虑因素 颗粒层功能是指颗粒层有不同的神经化学表型 单一形态的中间神经元内的中间神经元[4-9]。例如，单极画笔 细胞(UBC)和高尔基细胞可根据GABA水平分为神经化学亚型。 甘氨酸和代谢性谷氨酸受体(MGluRs)[5-7]。这种神经化学多样性并不是 无关紧要，但它为每种神经化学亚型提供了不同的功能角色。然而， 对不同形态和神经化学类型的颗粒层的反应知之甚少。 清醒行为动物的中间神经元。这些信息对于机械师来说是必不可少的 对小脑皮质功能的理解。我们的项目就是为了提供这些信息。 我们的目标是开始回答以下问题：执行的计算是什么 清醒动物不同级别的颗粒层中间神经元？这些计算有什么帮助 生成PC响应和行为？我们的实验将正面解决这些问题。我们的 模型系统是猕猴腹侧旁丘(VPFL)，这是一种参与小脑结构 眼球运动控制[10，11]。我们将使用单单元录音、药理学和行为学 测量。在目标1中，我们将鉴定不同形态和神经化学类型的颗粒 对中间神经元进行分层，研究它们对动眼任务的反应。在目标2中，我们将量化 药物扰乱颗粒层处理对PC的响应(唯一的输出 小脑皮质，AIM 2A)。我们还将量化药物对颗粒层的破坏作用。 眼动行为的加工(AIM 2B)。最后，在AIM 3中，我们将使用上述实验 检验VPFL，更具体地说，它的颗粒层，参与 建立眼球运动的内部表示(即眼球运动的正向模型) [12-16]。我们的初步数据表明，小脑皮质的颗粒层执行空间和 正常运动行为所必需的时间信号转换以及小脑皮质 参与构建运动的正向模型。实验方法和方法 初步数据证明，拟议的研究具有巨大的机械性潜力 了解颗粒层的功能。

ABSTRACT The granular layer is the input layer of the cerebellar cortex. It receives information from many brain areas through mossy fibers. It outputs information through granule cell axons to the molecular layer, where they contact other interneurons and Purkinje cells (PCs) [1-3]. Our deep understanding of the anatomy and physiology of the granular layer of the cerebellar cortex has made this structure an ideal model system to study signal processing by local networks. An important consideration when studying granular layer function is that there are different neurochemical phenotypes of granular layer interneurons within a single morphological phenotype of interneuron [4-9]. For instance, unipolar brush cells (UBCs) and Golgi cells can be divided into neurochemical subtypes based on the level of GABA- A, glycine and metabotropic glutamate receptors (mGluRs) [5-7]. This neurochemical diversity is not inconsequential, but it provides each neurochemical subtype with different functional roles. However, little is known about the response of different morphological and neurochemical types of granular layer interneurons in the awake behaving animal. This information is essential for a mechanistic understanding of cerebellar cortex function. Our project is designed to provide this information. Our goal is to begin answering the following questions: What are the computations performed by different classes granular layer interneurons in awake animals? How do these computations help generate PC responses and the behavior? Our experiments will tackle these questions head on. Our model system is the macaque ventral paraflocculus (VPFL), which is a cerebellar structure involved in oculomotor control [10, 11]. We will use single unit recordings, pharmacology, and behavioral measurements. In AIM 1, we will identify different morphological and neurochemical classes of granular layer interneurons and study their response to oculomotor tasks. In AIM 2, we will quantify the effect of pharmacological disrupting granular layer processing on the response of PCs (the sole output of the cerebellar cortex, AIM 2A). We will also quantify the effect of pharmacological disrupting granular layer processing on oculomotor behavior (AIM 2B). Lastly, in AIM 3, we will use the above experimental techniques to test the hypothesis that the VPFL, and more specifically its granular layer, participates in building an internal representation of the eye movement (i.e., a forward model of the eye movement) [12-16]. Our preliminary data suggest that the granular layer of the cerebellar cortex performs spatial and temporal signal transformations necessary for normal motor behavior and that the cerebellar cortex participates in the construction of a forward model of the movement. The experimental approach and preliminary data attest to the tremendous potential of the proposed studies to mechanistically understand granular layer function.