Cerebellar nuclei are the primary organizers of circuit formation in cerebellum

本研究计划旨在了解驱动早期小脑发育的机制。小脑对运动协调和非运动功能（如情感和认知）至关重要。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所有其他小脑细胞类型的模式。这一观点也暗示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。我的研究已经确定了CN神经元子集在建立小脑连接方面的意想不到的新作用。我的数据强烈表明，大约在浦肯野细胞诞生的前一天，CN可能接受了来自三叉神经的神经纤维接触。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神经元用来建立小脑神经元网络（传入神经纤维连接到传出神经元）作为发育中的小脑的主要组织者的遗传、细胞和分子机制。

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.