Synaptic mechanisms of auditory thalamic cross-modal communication

摘要 健康的受试者迅速转移他们的注意力，以响应动态的感觉环境和 不断变化的认知需求。未能在听觉和听觉之间快速转移感知资源 其他模式被认为是阅读障碍和自闭症的核心缺陷。准确地说 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 这表明丘脑包含的回路有能力在 不同的感官模式。具体地说，丘脑网状核(TRN)是 围绕丘脑的GABA能神经元可以作为沟通的纽带 在感觉丘脑的不同区域之间，这种现象我们称之为丘脑“交叉” 谈一谈。“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质通路之间切换。我们建议对此进行测试 使用解剖学、化学遗传学、光学刺激和光学的新组合的假说 小鼠的成像方法，使用切片和活体方法。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 听觉丘脑核团之间相互沟通。接下来，我们将确定是否和 这种丘脑串扰是如何在听觉皮质水平影响突触反应的。 最后，我们将直接从光学角度考察TRN对跨通道加工的影响 在清醒状态下对联合感觉刺激的皮质反应进行成像时调节TRN 老鼠。该项目的成功完成将提供第一个电路级的表征 TRN在听觉丘脑和其他丘脑区域之间的通讯中的作用。在……里面 此外，这项工作将为更好地理解丘脑网状结构 系统因交流障碍而崩溃。

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.