Functional architecture of the auditory cortex

描述(申请人提供)：这项研究的目标将是调查听觉皮质突触的突触特性，以评估它们在听觉信息处理中的假定作用。这项研究的广泛目标是了解这些投射对听觉感知和行为的功能贡献，以及这些突触属性如何随着年龄和疾病过程的变化而表现出来。我已经确定了中枢听觉系统中谷氨酸能突触的几个解剖学和生理学特性，这构成了拟议的研究的基础。这项研究将利用小鼠的体外切片制备，这是为听觉皮质通路开发的。大脑皮层神经元的全细胞记录将被用来记录对最小电刺激的反应，通过去掉谷氨酸的光刺激，以及对通道视紫红质表达纤维的光刺激，以表征它们的地形图组织和生理特性。此外，还将使用一种由自发荧光揭示的反应的光学成像的新方法来帮助跟踪听觉皮质投影的输出模式。将通过细胞内注射生物细胞素来寻找形态上的相关性。拟议的实验应有助于进一步深入了解听觉皮质投射的信息承载作用，并有助于确定它们在听觉系统中央处理组织中的相对权重。 公共卫生相关性：这项研究应该增强我们对听觉系统中正常信息处理模式的认识和视角。这将为进一步探索听神经疾病和衰老中的异常处理提供基础，最终将导致改善对听力系统疾病患者的诊断和治疗。

DESCRIPTION (provided by applicant): The goals of this study will be to investigate the synaptic properties of auditory cortical synapses, in order to assess their putative roles in auditory information processing. The broad objectives of this research are to understand the functional contributions of these projections to auditory perception and behavior and how changes in these synaptic properties manifest with age and in disease processes. I have already identified several anatomical and physiological properties of glutamatergic synapses in the central auditory system, which forms the basis for the proposed investigation. This study will utilize an in vitro slice preparation in the mouse, which has been developed for the auditory cortical pathways. Whole-cell recordings in cortical neurons will be used to record responses to minimal electrical stimulation, photostimulation by uncaging of glutamate, and photostimulation of channelrhodopsin expressing fibers in order to characterize their topographic organization and physiological properties. In addition, a novel method of optical imaging of responses revealed by autofluorescence will be employed to help trace the output patterns of auditory cortical projections. Morphological correlates will be sought using intracellular injections of biocytin. The proposed experiments should lead to further insight on the information-bearing roles of the auditory cortical projections, as well as help to establish their relative weights in the organization of central processing in the auditory system. PUBLIC HEALTH RELEVANCE: This study should enhance our knowledge and perspective of the normal modes of information processing in the auditory system. It should provide a foundation for the further exploration of abnormal processing in auditory neurological diseases and aging, which will eventually lead to improved diagnostics and treatments for patients with disorders of the auditory system.