Synaptic mechanisms of auditory thalamic cross-modal communication

摘要 健康的受试者会迅速转移注意力以响应动态的感官环境， 不断变化的认知需求。无法在听觉和听觉之间快速转移知觉资源 其他方式被假设为阅读障碍和自闭症的核心缺陷。正是如此 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 表明丘脑包含能够在不同状态之间快速转换的电路 不同的感官方式。具体来说，丘脑网状核（TRN）是一个薄壳， 丘脑周围的 GABA 能神经元可能充当沟通的纽带 感觉丘脑的不同区域之间存在这种现象，我们将这种现象称为丘脑“交叉” 说话。”根据最近的数据和我们的初步发现，我们假设 thalamo-TRN- 丘脑回路提供丘脑核之间的关键连接，因此允许快速 听觉通路和其他丘脑皮质通路之间的切换。我们建议对此进行测试 使用解剖学、化学遗传学、光刺激和光学的新颖组合的假设 小鼠成像方法，使用切片和体内方法。具体来说，我们将 确定多个潜在电路路径中的哪一个用于允许听觉、视觉和 听觉丘脑核团相互沟通。接下来，我们将确定是否以及 这种丘脑串扰如何影响听觉皮层水平的突触反应。 最后，TRN 对跨模态处理的影响将通过光学直接检查 调节 TRN，同时对清醒状态下组合感觉刺激的皮层反应进行成像 老鼠。该项目的成功完成将提供该器件的第一个电路级表征 TRN 在听觉丘脑和其他丘脑区域之间的交流中的作用。在 此外，这项工作将为更好地理解丘脑网状结构如何 系统因沟通障碍而崩溃。

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.