Auditory Cortical Processing and Plasticity in the Mouse

描述（由申请人提供）：本研究的目的是了解听觉信息是如何在皮层柱中转换的，以及这种转换是如何被听觉经验和学习所修改的。这一目标将通过对小鼠听觉皮层加工和可塑性的研究来实现，以便为未来的实验建立一个模型系统，该实验将利用现有的强大的遗传技术来操纵小鼠的皮层电路。本研究涉及三个具体目标：(1)为了表征小鼠听觉皮层皮层柱内发生的听觉信息转换，将比较初级听觉皮层（A1）和前听觉场（AAF）的核上层、核下层和丘脑受体层神经元的颞谱感受野（STRFs）。细胞外神经元记录将获得在频谱丰富，时间复杂的声刺激和strf将通过反向相关分析确定。(2)为了研究发育过程中的听觉体验如何改变皮层柱内听觉信息的转换，我们将在安静声环境中饲养的成年小鼠的strf与在发育过程中暴露于向上和向下频率扫描刺激的小鼠的strf进行比较。研究人员将分析两组动物皮层层之间以及A1和AAF区域之间strf的变化，以确定早期经历引起的皮层处理变化。(3)为了确定听觉学习如何改变听觉信息的皮层内转换，将成年小鼠的strf与暴露于相同刺激但未训练区分的小鼠的strf进行比较。我们将再次分析两组动物皮层层之间以及A1和AAF皮层区域之间strf的差异，以确定听觉学习引起的皮层加工的变化。最终，在正常小鼠中进行的这三个实验的结果旨在为未来在基因工程小鼠中进行的计划实验提供一个框架，这些实验将旨在确定不同皮层细胞类型在皮层加工和可塑性中的作用，并确定神经和神经精神疾病的皮层原因和后果。

DESCRIPTION (provided by applicant): The objective of this research is to understand how auditory information is transformed within cortical columns and how this transformation is modified by auditory experience and learning. This objective will be pursued through studies of auditory cortical processing and plasticity in the mouse, in order to establish a model system for future experiments that will exploit powerful genetic techniques now available for manipulating cortical circuitry in mice. The proposed investigations involve three specific aims: (1) To characterize the transformations of auditory information occurring within cortical columns in mouse auditory cortex, spectrotemporal receptive fields (STRFs) of neurons in supragranular, infragranular, and thalamorecipient layers of primary auditory cortex (A1) and anterior auditory field (AAF) will be compared. Extracellular neuronal recordings will be obtained during presentation of spectrally rich, temporally complex acoustic stimuli and STRFs will be determined by reverse-correlation analysis. (2) To examine how auditory experience during development might modify the transformations of auditory information within cortical columns, STRFs from adult mice reared in a quiet acoustic environment will be compared to STRFs from mice exposed during development to stimuli composed of upward and downward frequency sweeps. Variations in STRFs across cortical layers and between areas A1 and AAF will be analyzed for both groups of animals, to identify changes in cortical processing induced by early experience. (3) To determine how auditory learning modifies intracortical transformations of auditory information, STRFs from adult mice trained to discriminate stimuli composed of upward and downward frequency sweeps will be compared to STRFs from mice exposed to the same stimuli but not trained to discriminate them. Differences in STRFs between cortical layers and between cortical areas A1 and AAF will again be analyzed for both groups of animals, to define the changes in cortical processing induced by auditory learning. Ultimately, the results of these three experiments in normal mice are intended to provide a framework for future planned experiments in genetically engineered mice, experiments that will be aimed at defining the roles of different cortical cell types in cortical processing and plasticity, and at identifying the cortical causes and consequences of neurological and neuropsychiatric disease.