Thalamic reticular nucleus-specific Cre mice for functional interrogation

 描述(由申请人提供)：在现代神经科学中，信息如何作为行为状态的功能被传递到新皮质是一个基本但知之甚少的问题。丘脑网状核(TRN)是一种抑制结构，被认为是从丘脑到皮质的信息通路，但缺乏澄清这一过程细节的实验证据。为了克服这些限制，询问intac trn微电路，并了解它们在行为中的作用，我们将创造新的分子工具，赋予这种大脑结构基因靶向的特异性。使用创新的基因组编辑。 我们将最大限度地提高目标成功率，同时最大限度地减少验证这些工具所需的时间。使用这些工具，我们将询问TRN微电路是如何在功能上组织的，解决丘脑如何差异地选通多个相互竞争的输入以指导行为输出，Aim II。除了为进一步了解大脑微电路、状态调节和认知开辟几个场所外，这项研究将具有巨大的翻译影响。在Halassa和冯的平行合作中，我们正在研究具有原发TRN功能障碍的单基因人类自闭症小鼠模型。我们正在创造的遗传方法将使我们有能力开发分子和光学干预工具来治疗这种疾病和其他神经发育疾病。

 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.