Cerebellar nuclei are the primary organizers of circuit formation in cerebellum

小脑核团是小脑回路形成的主要组织者

• 批准号: 341921-2012
• 负责人: Marzban, Hassan
• 金额: $ 1.89万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572415
• 关键词: Cerebellar; nuclei; primary; organizers; circuit

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.

这项研究计划旨在了解驱动早期小脑发育的机制。小脑对于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。这一概念也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。我的研究已经确定了CN神经元的一个子集在建立小脑连接中的一个意想不到的和新颖的作用。我的数据强烈表明，CN可能会收到传入的神经纤维接触三叉神经大约一天前出生的浦肯野细胞。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（传入神经纤维连接到传出神经元）作为发育中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束示踪技术相结合，以确定拟议的新CN germinal区和正常和突变小鼠早期到达小脑传入纤维的起源。这项研究将大大提高我们对小脑回路形成的理解，并建立一套基本原则，这些原则可能对管理所有主要脑网络的构建都很重要。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。