Functional organization of auditory corticothalamic projection systems

描述(申请人提供)：项目摘要：建议研究的目标是了解听觉皮质和丘脑之间的功能关系，并最终揭示听觉认知的神经基础。这项工作将检验这样一种假设，即听觉丘脑的非丘脑部分在听觉皮质区域之间的另一条信息通路中起着连接作用：皮质-丘脑皮质通路，其中第5层听觉皮质丘脑投射为非丘脑非丘脑核团提供前馈驱动输入，而第6层皮质丘脑投射为听觉丘脑的所有区域提供反馈。为了验证这一想法，将通过向听觉皮质和丘脑注射示踪剂来研究小鼠大脑皮质和丘脑板层特异性皮质丘脑投射系统的相互作用模式和突触形态。此外，在听觉皮质丘脑切片的制备中，将研究丘脑驱动或调制反应的生理特征，方法是在记录听觉丘脑亚核神经元的同时，使用激光照射谷氨酸分别刺激第5层和第6层的听觉皮质丘脑神经元。最后，将记录一对相互连接的听觉皮质和丘脑神经元，以更好地定义皮质丘脑系统的详细电路。拟议的实验应该有助于阐明大规模、不同种类的皮质丘脑投射系统的作用(S)，并有助于阐明非丘脑在塑造听觉皮质功能方面的作用。此外，这项工作将是强化实验室培训经验的重点，旨在为研究人员为致力于研究丘脑皮质功能的研究生涯做好准备。这将与临床行为学和认知神经学的培训相结合，使研究人员能够制定策略，解决依赖于丘脑皮质网络完整性的更高皮质功能的问题。相关性：这项拟议研究的目标是更好地了解感知声音的大脑机制。人们希望这项工作将导致对言语感知的更好理解，并为诊断和治疗失去语言使用能力的患者提供新的方法。

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.