Synaptic mechanisms of auditory thalamic cross-modal communication

摘要 健康受试者迅速转移他们的注意力，以响应动态的感觉环境， 改变认知需求。无法快速在听觉和听觉之间转换感知资源， 其他形式被假设为是诵读困难和自闭症的核心缺陷。精确 大脑如何在感觉系统之间传递信息尚不清楚，但最近的研究表明， 表明丘脑含有能够快速转换的回路， 不同的感官形态具体来说，丘脑网状核（TRN），一个薄壳， 丘脑周围的GABA能神经元，可能作为一个链接，使通信 在感觉丘脑的不同区域之间，我们称之为丘脑“交叉- 说吧。”根据最近的数据和我们的初步发现，我们假设丘脑-TRN- 丘脑回路提供丘脑核团之间的关键连接，因此允许快速 在听觉和其他丘脑皮层通路之间切换。我们打算测试一下 使用解剖学、化学发生学、光学刺激和光学 成像方法在小鼠中，使用切片和体内方法。具体来说，我们将 确定使用多个潜在电路通路中的哪一个来允许听觉、视觉和 听觉丘脑核团相互沟通。接下来，我们将确定是否和 这种丘脑串扰如何影响听觉皮层水平的突触反应。 最后，TRN对交叉模态处理的影响将直接通过光学检查。 在成像皮质对清醒时组合感觉刺激的反应时调节TRN 小鼠该项目的成功完成将提供 TRN在听觉丘脑和其他丘脑区域之间的通信中的作用。在 此外，这项工作将奠定基础，更好地了解如何丘脑网状 系统在交流的混乱中崩溃。

ABSTRACT Healthy subjects rapidly shift their attention in response to a dynamic sensory environment and changing cognitive demands. Failure to quickly shift perceptual resources between auditory and other modalities has been hypothesized to be a core deficit in both dyslexia and autism. Precisely how the brain shuttles information between sensory systems is not known, but recent work suggests that the thalamus contains circuits that have the capacity to rapidly transition between different sensory modalities. Specifically, the thalamic reticular nucleus (TRN), a thin shell of GABAergic neurons surrounding the thalamus, may serve as a link to allow communication between different areas of the sensory thalamus, a phenomenon we refer to as thalamic “cross- talk.” Based on recent data and our preliminary findings, we hypothesize that thalamo-TRN- thalamic circuits provide critical connections between thalamic nuclei and therefore permit rapid switching between auditory and other thalamocortical pathways. We propose to test this hypothesis using a novel combination of anatomical, chemogenetic, optical stimulation and optical imaging approaches in the mouse, using both slice and in vivo approaches. Specifically, we will determine which of multiple potential circuit pathways is/are used to permit auditory, visual and auditory thalamic nuclei to communicate with each other. Next, we will determine whether and how such thalamic cross-talk influences synaptic responses at the level of the auditory cortex. Finally, the impact of the TRN on cross-modal processing will be directly examined by optically modulating the TRN while imaging cortical responses to combined sensory stimulation in awake mice. Successful completion of this project will provide the first circuit-level characterization of the role of the TRN in communication between the auditory thalamus and other thalamic regions. In addition, this work will lay the groundwork for a greater understanding of how thalamoreticular systems break down in disorders of communication.