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. ? ?
