Imaging adaptive cerebellar processing at cellular resolution in awake mice

描述（由申请人提供）：小脑对运动的控制、感觉加工以及认知和情绪功能的调节很重要。成年后，这一区域的损伤会导致日常生活中的衰弱问题；在婴儿期，小脑损伤会显著增加患自闭症（一种神经发育障碍）的风险。这个实验室的长期目标是了解小脑的早期损伤是如何导致自闭症症状的。特别是，拟议中的实验将使用新技术来研究个体小脑神经元的功能，这些神经元参与了清醒小鼠、正常小鼠和具有导致人类自闭症的遗传缺陷小鼠学习预测可预测事件的过程。这个应用程序的总体目标是了解清醒、有行为的动物小脑的功能，然后利用这些信息来了解自闭症谱系障碍小鼠模型中这一回路是如何出现故障的。这一贡献意义重大，因为它将产生在现实条件下重要神经回路功能的详细和综合知识，并将这些知识应用于常见的神经发育障碍。这种方法是创新的，因为这个实验室已经开发出了工具，可以研究以前不能在清醒的动物身上检查的细胞。因此，在本应用程序中提出的工作将促进对导致自闭症的基因突变如何影响神经回路功能的了解。从长远来看，这些信息可能会导致自闭症谱系障碍的诊断、治疗和预防的新方法。

DESCRIPTION (provided by applicant): The cerebellum is important for the control of movement, sensory processing, and regulation of cognitive and emotional function. In adulthood, damage to this region in adulthood leads to debilitating problems with everyday life; in infancy, cerebellar damage dramatically increases the risk of autism, a neurodevelopmental disorder. The long-term goal of this laboratory is to understand how early damage to the cerebellum can lead to symptoms of autism. In particular, the proposed experiments will use new technologies to study the function of individual cerebellar neurons that are involved in learning to anticipate predictable events in both awake mice, both normal and in mice with genetic defects that cause autism in humans. The overall objective of this application is to understand the function of the cerebellum in awake, behaving animals and then to use that information to understand how this circuit malfunctions in mouse models of autism spectrum disorder. This contribution is significant because it will produce detailed and integrated knowledge of the function of an important neural circuit under realistic conditions and apply that knowledge to a common neurodevelopmental disorder. This approach is innovative because this laboratory has developed tools that allow the study of cells that previously could not be examined in awake animals. The work proposed in this application will therefore advance knowledge of how the genetic mutations that cause autism influence the function of neural circuits. In the long run, this information could lead to new approaches to diagnosis, treatment, and prevention of autism spectrum disorder.