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如何在皮质柱内转换，以及这种转换如何通过听觉经验和学习进行修改。这一目标将通过对小鼠听觉皮层处理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，该实验将利用目前可用于操纵小鼠皮层电路的强大遗传技术。（1）比较初级听皮层（A1）颗粒上、颗粒下和丘脑感受器层神经元的谱时感受野（STRFs）和前听野（AAF），以表征听觉信息在皮层柱内的转换。细胞外神经元记录将在呈现频谱丰富、时间复杂的声刺激期间获得，并且将通过反向相关分析来确定STRF。(2)为了研究如何在发展过程中的听觉经验可能会修改皮质柱内的听觉信息的转换，从成年小鼠在安静的声学环境饲养的STRF将比较从小鼠暴露在发展过程中的刺激组成的向上和向下的频率扫描。将对两组动物的皮质层和A1区与AAF区之间的STRF变化进行分析，以确定早期经验诱导的皮质处理变化。(3)为了确定听觉学习如何改变听觉信息的皮质内转换，将来自训练区分由向上和向下频率扫描组成的刺激的成年小鼠的STRF与来自暴露于相同刺激但未训练区分它们的小鼠的STRF进行比较。将再次分析两组动物皮层层之间以及皮层A1区和AAF区之间的STRF差异，以确定听觉学习诱导的皮层处理变化。最终，在正常小鼠中的这三个实验的结果旨在为未来计划在基因工程小鼠中进行的实验提供框架，这些实验旨在定义不同皮质细胞类型在皮质加工和可塑性中的作用，并确定神经系统和神经精神疾病的皮质原因和后果。

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.