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Mapping cerebellar granule cell function with novel genetic and optical tools

利用新型遗传和光学工具绘制小脑颗粒细胞功能图

基本信息

批准号：
10001987
负责人：
Gerard Joey Broussard
金额：
$ 7.03万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-17 至 2022-09-16
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10001987
关键词：
Address Anatomy Animal Model Animals Attention deficit hyperactivity disorder Axon BRAIN initiative Behavioral Behavioral Paradigm Biophysics Brain Brain region Calcium Cell physiology Cerebellar Cortex Cerebellum Code Collaborations Communication Complex Decision Making Dissection Distant Electrophysiology (science)Event Failure Fiber Fluorescence Functional Magnetic Resonance Imaging Genetic Glass Goals Human Image Individual Influentials Kinetics Laboratories Lateral Link Location Maps Medial Methodology Methods Modeling Motor Movement Disorders Mus Neocortex Neurons Occupations Optics Output Pathway interactions Pattern Population Preparation Property Prosencephalon Proteins Purkinje Cells Research Research Design Research Personnel Rewards Rodent Role Sampling Schizophrenia Sensory Signal Transduction Slice Stream Structure Surface System Techniques Technology Testing Time Training autism spectrum disorder calcium indicator cell transformation cortex mapping cranium design experimental study granule cell human model imaging study improved in vivo Model in vivo imaging mossy fiber neocortical nervous system disorder neuronal cell body novel optogenetics reconstruction response sensor sensory stimulus spatiotemporal stem temporal measurement theories tool

项目摘要

Project Summary/Abstract Recent evidence from multiple laboratories in both human and animal models supports a role for the granule cell (GrC) pathway of the cerebellum in representing a wide range of sensory, motor, and internal information. Classical theories of cerebellar function proposed that activity in a small number of GrCs (<1%) encodes a particular sensorimotor context. However, recent population level calcium imaging studies of GrC somata indicate that populations of GrCs encode sensory and motor events, and complex properties such as reward and motor preparation. However, these studies lacked the temporal resolution to identify specific relationships between those events and GrC firing. Both study designs also precluded direct determination of what input pathways drove the observed patterns of GrC activity. A comprehensive understanding of the input-output transform performed by GrCs will require the ability to precisely perturb anatomically specific descending inputs while densely recording the resultant patterns of activity with high spatiotemporal precision. To approach this set of methodological gaps, I propose to (1) holistically develop a spike-counting method for genetically encoded indicators (GECIs) by adjusting current sensor properties and creating a biophysical in vivo model of the calcium sensor GCaMP, (2) optogenetically perturb neocortex to map its functional inputs to GrCs while optically accessing the entire cerebellar surface, and (3) use a rodent behavioral task to disambiguate sensory, motor and internal-state contributions to granule cell activity patterns. Completion of these aims will allow a direct test of whether GrCs indeed make a sparse representation of their input signals. I also aim to provide the most comprehensive analysis to date on the makeup of the inputs that drive GrC activity.

项目总结/文摘