Models of the Cerebellar Purkinje Cell and Cortex

小脑浦肯野细胞和皮质模型

• 批准号: 0517572
• 负责人: James Bower
• 金额: $ 54.09万
• 依托单位: University of Texas Health Science Center San Antonio
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0517572&HistoricalAwards=false
• 关键词: Models; Cerebellar; Purkinje; Cell; Cortex

Award AbstractFor 150 years the cerebellum has been assumed to be primarily involved in regulating movement. In addition, most functional models of cerebellar movement control are based on a 100 year old understanding of the anatomical and physiological organization of this structure. Over the last 10 years, however, evidence has accumulated that the cerebellum may be involved in much more than just movement control. Paralleling this rather dramatic change in thinking about overall cerebellar function, recent experimental results also suggest that the standard functional interpretation of the organization of cerebellar circuits may also require significant revision. Specifically, most cerebellar models and theories are based on the assumption that the 150,000 parallel fiber excitatory synaptic inputs provided each cerebellar Purkinje cell (the largest excitatory synaptic convergence for any cell in the mammalian nervous system) directly drive the generation of Purkinje cell action potentials, i.e., their output. Accumulating experimental and modeling evidence suggests that this is not the case. The research supported here uses a combination of realistic computer modeling techniques, electrophysiology, and anatomy to better understand the apparent lack of direct excitatory influence of this massive synaptic convergence on Purkinje cells in the rat. In particular, this research is focused on the functional role played by cerebellar cortical inhibitory neurons, which have largely been overlooked, in current theories of cerebellar function. The specific hypothesis tested is that inhibition in the so-called molecular layer of the cerebellum dynamically counteracts the excitatory effect of the parallel fibers, turning the parallel fiber / molecular layer inhibitory system into a modulatory, rather than a direct driving, influence. The results are expected to provide a new foundation for our rapidly expanding and evolving understanding of the functional organization of the cerebellar cortical network, and accordingly a new foundation for considering the general role of the cerebellum in the mammalian brain. The research will also provide research involvement for individuals from groups typically underrepresented in science.

奖项摘要150年来，小脑一直被认为主要参与调节运动。 此外，小脑运动控制的大多数功能模型都是基于对该结构的解剖和生理组织的100年前的理解。 然而，在过去的10年里，越来越多的证据表明小脑可能不仅仅参与运动控制。最近的实验结果也表明，对小脑回路组织的标准功能解释可能也需要进行重大修改。具体地说，大多数小脑模型和理论都是基于这样的假设，即提供给每个小脑浦肯野细胞（哺乳动物神经系统中任何细胞的最大兴奋性突触会聚）的150，000个平行纤维兴奋性突触输入直接驱动浦肯野细胞动作电位的产生，即，他们的输出。 积累的实验和建模证据表明，情况并非如此。 这里支持的研究使用了逼真的计算机建模技术，电生理学和解剖学的结合，以更好地理解这种大规模突触会聚对大鼠浦肯野细胞的直接兴奋性影响的明显缺乏。特别是，这项研究的重点是小脑皮质抑制神经元，这在很大程度上被忽视，在目前的小脑功能理论所发挥的功能作用。 测试的特定假设是，在小脑的所谓的分子层的抑制动态地抵消了平行纤维的兴奋效应，把平行纤维/分子层抑制系统变成一个调制，而不是直接驱动，影响。 这些结果有望为我们对小脑皮质网络功能组织的快速扩展和不断发展的理解提供新的基础，并因此为考虑小脑在哺乳动物大脑中的一般作用提供新的基础。 这项研究还将为来自科学界通常代表性不足的群体的个人提供研究参与。