Functional organization of auditory corticothalamic projection systems

描述（由申请人提供）：项目概述：拟议研究的目的是了解听觉皮层和丘脑之间的功能关系，并最终揭示听觉认知的神经基质。这项工作将测试的假设，即听觉丘脑的nonlemniscal部分作为一个链接，在一个替代的信息路线之间的听觉皮层区域：皮质-丘脑皮质的路线，与第5层的听觉皮质丘脑的预测提供前馈驱动输入的nonlemniscal丘脑核，而第6层皮质丘脑的预测提供反馈给所有地区的听觉丘脑。为了验证这一想法，将使用示踪剂注射到听觉皮层和丘脑中来研究小鼠中特定皮层丘脑投射系统的互惠模式和突触形态。此外，在丘脑中的驱动器或调制器响应的生理特征将在听觉皮质丘脑切片制备中进行研究，通过使用谷氨酸的激光释放来分别刺激第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中的神经元。最后，成对的连接的听觉皮层和丘脑神经元将被记录，以更好地定义详细的皮质丘脑系统的电路。拟议的实验应该阐明的作用（S）的大规模，异质性皮质丘脑投射系统，以及帮助澄清的作用，非丘系丘脑在塑造听觉皮层功能。此外，这项工作将是一个密集的实验室培训经验的重点，旨在为研究人员准备一个研究生涯致力于研究听觉丘脑皮质功能。这将与临床失语症学和认知神经学的培训相结合，使研究者能够制定策略，以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：拟议研究的目标是更好地了解感知声音的大脑机制。希望这项工作将导致更好地理解言语感知，并找到新的方法来诊断和治疗失去语言使用能力的患者。

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.