Cerebellar nuclei are the primary organizers of circuit formation in cerebellum

本研究旨在了解小脑早期发育的机制。小脑对运动协调至关重要，对情绪和认知等非运动功能也是如此。两种主要类型的神经元调节小脑功能：浦肯野细胞和小脑核(CN)神经元。人们普遍认为，浦肯野细胞指导着所有其他类型的小脑细胞的构型。这一概念还意味着，浦肯野细胞是到达小脑的早期神经纤维的目标，这些神经纤维被认为起源于前庭神经。我的研究发现，CN神经元的一个子集在建立小脑连接方面扮演了一个意想不到的新角色。我的数据有力地表明，大约在浦肯野细胞出生前一天，CN可能接受来自三叉神经的传入神经纤维接触。有趣的是，这些CN神经元似乎起源于一个新的生发区。本研究的目的是确定CN神经元用于建立小脑神经元网络(传入神经纤维与传出神经元的连接)作为发育中的小脑的主要组织者的遗传、细胞和分子机制。 我将使用免疫细胞化学和轨迹追踪技术相结合的方法，在正常和突变小鼠中识别拟议的新的CN生发区和早期到达的小脑传入纤维的来源。这项研究将极大地增强我们对小脑回路形成的理解，并建立一套可能对管理所有主要大脑网络的构建至关重要的基本原则。拟议的工作将为加拿大神经科学领域的研究科学家提供广泛的高素质人员(HQP)培训机会。

This research program is aimed at understanding the mechanism driving early cerebellar development. The cerebellum is critical for motor coordination and also for non-motor functions such as emotion and cognition. Two major types of neurons regulate cerebellar function: Purkinje cells and cerebellar nuclei (CN) neurons. It is widely thought that Purkinje cells direct the patterning of all other cerebellar cell types. This notion also implies that the Purkinje cells are the targets of the early nerve fibers arriving in the cerebellum, which are thought to originate from the vestibular nerve. My research has identified an unexpected and novel role for a subset of CN neurons in setting up cerebellar connectivity. My data strongly suggest that CN may receive incoming nerve fibers contacts from the trigeminal nerve about one day before the birth of Purkinje cells. Interestingly, these CN neurons appear to originate from a new germinal zone. The goal of this study is to determine the genetic, cellular, and molecular mechanisms that CN neurons use to establish the cerebellar neuronal network (incoming nerve fiber connection to the outgoing neuron) as a principal organizer of the developing cerebellum. I will use a combination of immunocytochemistry and tract tracing techniques to identify the proposed new CN germinal zone and the origin of the early arriving cerebellar incoming fibers in normal and mutant mice. This study will greatly enhance our understanding of cerebellar circuit formation and establish a set of basic principles that may be important for governing the construction of all major brain networks. The proposed work will provide a wide range of training opportunities for highly qualified personnel (HQP) for Canadian research scientists in the field of neuroscience.