Imaging adaptive cerebellar processing at cellular resolution in awake mice

以细胞分辨率对清醒小鼠的适应性小脑处理进行成像

基本信息

批准号：
8820398
负责人：
Samuel Sheng-Hung Wang
金额：
$ 42.82万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-12-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8820398
关键词：
Accounting Adult Affect Anatomy Animal Model Animals Association Learning Autistic Disorder Behavior Blinking Brain Cells Cerebellar Diseases Cerebellum Code Cognitive Cognitive deficits Computer Simulation Defect Dendrites Development Diagnosis Disease Emotional Event Fiber Gene Mutation Genes Goals Head Human Image Individual Influentials Knowledge Laboratories Lead Learning Life Measures Methods Mission Modeling Monozygotic twins Motor Movement Multiphoton Fluorescence Microscopy Mus Mutation National Institute of Neurological Disorders and Stroke Neurodevelopmental Disorder Neurons Pathway interactions Pattern Physiological Population Prevention Process Proteins Public Health Purkinje Cells Reaction Time Regulation Research Resolution Risk Sensory Sensory Process Shapes Signal Transduction Slice Staging Structure Study models Symptoms Testing Time Translating Virus Work autism spectrum disorder awake base behavior test burden of illness calcium indicator cell type computer framework conditioning developmental disease endophenotype expectation granule cell in vivo imaging infancy innovation mossy fiber mouse model neural circuit neuropsychiatry new technology novel strategies postnatal prevent public health relevance relating to nervous system research study response risk variant sensory stimulus tool

项目摘要

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.

描述（由申请人提供）：小脑对于运动控制、感觉处理以及认知和情绪功能的调节很重要。在成年期，该区域的损伤会导致日常生活中的衰弱问题；在婴儿期，小脑损伤会大大增加患自闭症（一种神经发育障碍）的风险。该实验室的长期目标是了解小脑的早期损伤如何导致自闭症症状。特别是，拟议的实验将使用新技术来研究单个小脑神经元的功能，这些神经元参与学习预测清醒小鼠（包括正常小鼠和具有导致人类自闭症的遗传缺陷的小鼠）中可预测事件的功能。该应用的总体目标是了解清醒、行为动物的小脑功能，然后利用该信息来了解自闭症谱系障碍小鼠模型中该回路如何发生故障。这一贡献意义重大，因为它将产生关于现实条件下重要神经回路功能的详细和综合的知识，并将该知识应用于常见的神经发育障碍。这种方法具有创新性，因为该实验室开发了一些工具，可以研究以前无法在清醒动物身上进行检查的细胞。因此，本申请中提出的工作将增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，这些信息可能会带来诊断、治疗和预防自闭症谱系障碍的新方法。