Thalamic reticular nucleus-specific Cre mice for functional interrogation

用于功能询问的丘脑网状核特异性 Cre 小鼠

基本信息

批准号：
9062515
负责人：
Michael M Halassa
金额：
$ 25.09万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-15 至 2018-01-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9062515
关键词：
Address Autistic Disorder Autopsy Behavior Behavioral Brain Brain region Cell Nucleus Cells Clinical Cognition Cognitive Collaborations Communication Complement Data Disease Dissection Engineering Exhibits Functional disorder Genetic Genetic Models Health Human Methods Modality Modeling Molecular Mus Neocortex Neurodevelopmental Disorder Neurons Neurosciences Nuclear Optics Output Perception Physiological Physiology Positioning Attribute Process Prosencephalon Psychiatrist Psychophysics Regulation Research Rodent Model Role Schizophrenia Scientist Sensory Sleep Slice Specificity Stream Structure Technology Thalamic structure Time Transgenic Animals Transgenic Mice Variant Whole-Cell Recordings base cell type cognitive control cognitive function experience genome editing in vivo innovation knockout gene mouse model neuropsychiatric disorder neuropsychiatry novel overexpression recombinase sensory gating sensory stimulus success tool translational study

项目摘要

DESCRIPTION (provided by applicant): How information is routed to the neocortex as a function of behavioral state is a fundamental but poorly understood question in modern neuroscience. The thalamic reticular nucleus (TRN) is an inhibitory structure that is hypothesized to gate information throughput from thalamus to cortex, but experimental evidence clarifying the details of this process is lacking. To overcome these limitations, interrogate intac TRN microcircuits and understand their role in behavior we will create novel molecular tools that confer genetic targeting specificity to this brain structure Aim I. Using innovative genome editing technologies, we will maximize targeting success, while minimizing the time taken to validate these tools. Using these tools, we will ask how TRN microcircuits are functionally organized addressing how the thalamus may differentially gate multiple competing inputs to guide behavioral output, Aim II. In addition to opening several venues for further basic understanding of brain microcircuits, state regulation and cognition, this research will be of tremendous translational impact. In a parallel collaboration between Halassa and Feng, we are studying a mouse model of monogenic human autism with a primary TRN dysfunction. The genetic methods we are creating will equip us with the ability to develop molecular and optical interventional tools for treatment of this disorder and other neurodevelopmental diseases.

描述（由适用提供）：在现代神经科学中，如何将信息路由到新皮层作为行为状态的函数是一个基本但知之甚少的问题。丘脑网核（TRN）是一种抑制性结构，假设从丘脑到皮质的门信息吞吐量，但是实验证据阐明了此过程的细节。为了克服这些局限技术，我们将最大限度地提高目标成功，同时最大程度地减少验证这些工具所花费的时间。使用这些工具，我们将询问TRN微电路如何在功能上组织起来，以解决丘脑如何差异化栅极多个竞争输入以指导行为输出，AIM II。除了开设几个场所以进一步理解大脑微电路，州调节和认知外，这项研究还将具有巨大的翻译影响。 Halassa和Feng之间的并行协作，我们正在研究具有主要TRN功能障碍的单基因自闭症的小鼠模型。我们正在创建的遗传方法将使我们能够开发分子和光学介入的工具来治疗这种疾病和其他神经发育疾病。