Functional organization of auditory corticothalamic projection systems

项目简介：拟开展的研究旨在了解听觉皮层与丘脑之间的功能关系，并最终揭示听觉认知的神经基础。这项工作将验证一个假设，即听觉丘脑的非丘脑部分在听觉皮质区域之间的替代信息通路中起着链接作用：皮质-丘脑通路，第5层听觉皮质丘脑投影向非丘脑核提供前馈驱动输入，而第6层皮质丘脑投影向听觉丘脑的所有区域提供反馈。为了验证这一想法，将通过向听觉皮层和丘脑注射示踪剂来研究小鼠层状特异性皮质丘脑投影系统的互易模式和突触形态。此外，在听觉皮质丘脑切片制备过程中，我们将利用谷氨酸激光释放分别刺激第5层和第6层的听觉皮质丘脑神经元，同时记录听觉丘脑亚核神经元，研究丘脑驱动或调节反应的生理特征。最后，成对连接的听觉皮层和丘脑神经元将被记录下来，以更好地定义皮层-丘脑系统的详细电路。所提出的实验应阐明大量的、异质的皮质丘脑投射系统的作用，并有助于阐明非皮质丘脑在形成听觉皮质功能中的作用。此外，这项工作将成为强化实验室培训经验的重点，旨在为致力于听觉丘脑皮质功能研究的研究人员做好准备。这将与临床失语学和认知神经学的培训相结合，使研究者能够制定策略来解决依赖于丘脑皮质网络完整性的高级皮质功能问题。相关性：这项研究的目的是为了更好地理解声音感知背后的大脑机制。人们希望这项工作能让人们更好地理解语言感知，并找到诊断和治疗失去语言使用能力的患者的新方法。

DESCRIPTION (provided by applicant): Project Summary: The objective of the proposed studies is to understand the functional relationships between the auditory cortex and thalamus, and ultimately to uncover the neural substrates for auditory cognition. This work will test the hypothesis that the nonlemniscal portions of the auditory thalamus act as a link in an alternate information route between auditory cortical areas: a cortico-thalamocortical route, with layer 5 auditory corticothalamic projections providing feedforward driving input to the nonlemniscal thalamic nuclei while layer 6 corticothalamic projections provide feedback to all areas of the auditory thalamus. To test this idea, the reciprocity patterns and synaptic morphologies of laminar-specific corticothalamic projection systems in the mouse will be studied using injections of tracers into both the auditory cortex and thalamus. In addition, the physiologic signatures of driver or modulator responses in the thalamus will be studied in the auditory corticothalamic slice preparation by using laser-uncaging of glutamate to stimulate auditory corticothalamic neurons in layers 5 and 6, respectively, while recording from neurons in the subnuclei of the auditory thalamus. Finally, pairs of connected auditory cortical and thalamic neurons will be recorded from to better define the detailed circuitry of corticothalamic systems. The proposed experiments should shed light on the role(s) of the massive, heterogeneous corticothalamic projection systems as well as help to clarify the role of the nonlemniscal thalamus in shaping auditory cortical function. In addition, this work will be the focus of an intensive laboratory training experience designed to prepare the investigator for a research career dedicated to the study of auditory thalamocortical function. This will be coupled with training in clinical aphasiology and cognitive neurology to enable the investigator to develop strategies to address problems of higher cortical function that depend upon the integrity of thalamocortical networks. Relevance: The goal of the proposed research is to better understand the brain mechanisms underlying the perception of sound. It is hoped that this work will lead to a better understanding of speech perception and to new ways to diagnose and treat patients who have lost their ability to use language.