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Cell Type-Specific Halorhodopsin Mice for Neuronal Silencin

用于神经元沉默的细胞类型特异性盐视紫红质小鼠

基本信息

批准号：
8469592
负责人：
Guoping Feng
金额：
$ 23.23万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8469592
关键词：
Acute Address Alleles Autistic Disorder Bacterial Artificial Chromosomes Behavior Brain Cations Chloride Ion Chlorides Communities Complex Corpus striatum structure Development Disease Electroporation Engineering Ensure Epilepsy Exhibits Functional disorder Gene Expression Gene Expression Profile Genes Genetic Goals Halorhodopsins In Situ Hybridization Injection of therapeutic agent Interneurons Knock-in Mouse Label Laboratories Lasers Light Maps Mediating Membrane Mental disorders Molecular Mus Nervous system structure Neurologic Neurons Neurosciences Parvalbumins Pattern Population Population Heterogeneity Property Pump Research Proposals Role Series Shapes Slice Speed Techniques Testing Transgenes Transgenic Mice Transgenic Organisms Viral Virus Work base brain shape cell type cholinergic neuron cohort dopaminergic neuron electrical property experience genetic manipulation human disease improved in vivo interest mouse genome mouse model nervous system disorder neural circuit neuropsychiatry optogenetics photoactivation promoter recombinase relating to nervous system tool transgene expression

项目摘要

DESCRIPTION (provided by applicant): The complex and diverse functions of the brain depend on the unique properties of neural circuits formed by various subtypes of neurons with distinct molecular and/or electrical properties. Furthermore, many neurological and psychiatric disorders are often due to the dysfunction of specific subsets of neurons or neural circuits. Thus, elucidating the unique roles of each subtype of neurons in shaping circuitry function is critical t our understanding of both normal and abnormal brain functions. Genetic tools that incorporating spatial and temporal control over neural activity in neuronal subsets would greatly enhance our capability to precisely map circuitry function and dysfunction in the brain. Manipulating activity n this way requires a tool that can be genetically targeted to specific populations of neurons and that allows simple and rapid control of neuronal firing. This has been made possible by the recent development of the genetically encoded light-activated cation channel channelrhodopsin-2 (ChR2) for photoactivation and the light-driven chloride pump halorhodopsin (NpHR) for photoinhibition. Recent studies from several laboratories have highlighted the tremendous potentials of using ChR2 and NpHR in mapping neuronal connectivity and manipulating circuitry function. The goal of this research proposal is to generate a series of transgenic mice that express improved NpHR selectively in molecularly defined subtypes of neurons in the brain. Together with our recently generated cell type-specific ChR2 transgenic mice, it will provide a set of powerful genetic tools for interrogating brain circuitry function and dysfunction using high speed photostimulation and photoinhibition in brain slices and in vivo.

描述（由申请人提供）：大脑的复杂和多样的功能依赖于由具有不同分子和/或电性质的各种神经元亚型形成的神经回路的独特性质。此外，许多神经和精神疾病通常是由于特定神经元亚群或神经回路的功能障碍。因此,