Cerebellar Microcircuits: Organization & Development

单极刷状细胞(UBC)是位于小脑颗粒层和大脑皮质的中间神经元。 含有耳蜗核复合体区域的颗粒细胞。在小脑皮质，UBC和 颗粒细胞共用苔藓纤维输入，代表仅有的两个兴奋性谷氨酸能神经元 上课。在啮齿动物中，UBC的分布比其他哺乳动物更有限，并且大量存在于 前庭-小脑小叶，在中线蚯蚓的其他小叶中有少量突起。横穿 哺乳动物物种，UBC优先与感觉输入系统相关，当它们出现时 避开主要以皮质-桥脑-小脑通路为靶点的区域。UBC通常会 只有一个以树突为终末的树突；它们建立了一个巨大的兴奋性突触 有苔藓纤维的玫瑰花状末端；UBC轴突在颗粒细胞之间分支，形成一个 非常独特的皮质固有系统，由苔藓纤维状分支组成。UBC，一对一 巨型突触被认为放大了单个纤维的输入，并同步了 数百个靶颗粒细胞，从而影响覆盖的浦肯野细胞亚群的放电模式。 而在小脑，UBC在尾叶、顶叶和外侧小叶中密度较高 由初级和次级前庭纤维支配，在耳蜗核复合体中，它们的密度是 在多感觉神经支配的背侧核中最高。因此，这个概念被提了出来。 这些独特的神经元对于调节头部在太空中的位置、影响姿势和 眼球运动和改善听觉表现。先前的证据表明，不列颠哥伦比亚省的人口 在化学上是异质性的，由两种主要的化学类型组成，一种表达钙的子集 结合蛋白Calretinin和表达代谢性谷氨酸的Calretinin阴性亚群 受体mGluR1a。在这场竞争性的更新中，私家侦探和他的合作者提议测试个人 UBC子类的属性与特定类型的输入相关的假设的各方面， 存在额外亚类特定的化学类型，以及由UBC轴突传递的输入质量 影响小脑网络。特定目标将分析UBC可能的子分类特定输入， 研究它们的发育可塑性和电生理特性，寻找新的脐带血 化学类型和研究UBC激发对网络的影响。拟议的研究是基于 多学科方法，将主要集中在老鼠身上，以利用可获得性 具有遗传遗传神经缺陷的突变动物品系以及细菌 人工染色体-表达增强型绿色荧光蛋白(EGFP)的转基因小鼠 在特定启动者的控制下。

The Unipolar Brush Cells (UBCs) are interneurons situated in the cerebellar granular layer and in granule cell containing regions of the cochlear nuclear complex. In the cerebellar cortex, UBCs and granule cells share mossy fiber inputs and represent the only two excitatory glutamatergic neuron classes. In rodents, UBCs have a more restricted distribution than in other mammals and abound in vestibulo-cerebellar lobules, with minor contingents in other lobules of the midline vermis. Across mammalian species, UBCs are preferentially associated with sensory input systems, while they appear to eschew regions targeted primarily by the cortico-ponto-cerebellar pathway. The UBC has typically only one dendrite that terminates with a brush of dendrioles; these establish a giant excitatory synapse with the rosette-like terminal of a mossy fiber; UBC axons ramify among granule cells and form a strikingly unique, cortex-intrinsic system of mossy fiber-like branches. The UBC, with its one-to-one giant synapse, is thought to amplify the input of an individual fiber and synchronize the activity of hundreds of target granule cells, thus influencing the firing pattern of subsets of overlying Purkinje cells. While in cerebellum UBCs are highly enriched in the caudal vermal and lateral lobules densely innervated by primary and secondary vestibular fibers, in the cochlear nuclear complex their density is highest in the polysensory innervated dorsal nucleus. Consequently, the notion has been put forward that these unique neurons are important for regulating head position in space, influencing posture and eye movements and improving auditory performance. Previous evidence indicates the UBC population is chemically heterogeneous and consists of two main chemotypes, a subset expressing the calcium binding protein calretinin, and a calretinin-negative subset expressing the metabotropic glutamate receptor mGluR1a. In this competitive renewal, the P.I. and his collaborators propose to test individual facets of the hypotheses that the properties of UBCs subclasses are related to specific types of inputs, that additional subclass specific chemotypes exist, and that input qualities transmitted by the UBC axon affect the cerebellar network. Specific aims will analyze possible sublineage specific inputs of UBCs, investigate their developmental plasticity and electrophysiologic properties, search for novel UBC chemotypes and study the network impact of UBC excitation. The proposed research is based on multidisciplinary approaches and will be primarily centered on mice to take advantage of the availability of strains of mutant animals with genetically transmitted neurological defects as well as of bacterial artificial chromosome (BAC)-transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of a specific promoter.