Electrophysiological studies in the visual and somatosensory cortices have shown that activation of inhibitory local circuit neurons (utilizing GABA) generate important, features of cortical sensory maps such as orientations sensitivity and receptive field size. In contrast, nothing is known concerning the role of GABA-ergic interneurons in the generation of auditory cortical maps. Recent pilot data has revealed evidence of a preferential orientation of inhibitory axonal networks which are orthogonal to the isofrequency lines of the tonotopic map (McMullen, 1990). These GABA-ergic cells may participate in the formation of binaural or tonotopic maps through feedforward lateral inhibition. The goal of the present study is to label target cells more reliably and completely using intracellular injection, and to relate their axonal arbors to the patch-like termination of thalamocortical afferents in the same preparation. The intracortical circuits of adjacent pyramidal cells will also be analyzed so that both excitatory and inhibitory cortical pathways may be characterized. Thalamocortical afferents (TC) arising from the medial geniculate body of the thalamus will be anterogradely labeled with the lectin PHA-L or rhodamine. After suitable survival, cortical slices through the auditory cortex will be made with a tissue chopper. Single cells in the living cortical slice will be impaled with a microelectrode and filled iontophoretically with FITC-labeled HRP. Immuno- and histochemical methods will be used to visualize the thalamocortical afferents and the dendritic and axonal arbors of injected cells in the same tissue slice. The axonal and dendritic territories of the filled cells will be reconstructed in 3-dimensions with a computer microscope system. We will also digitize the patchlike terminal territories of TC afferents. The morphological and transmitter-based dichotomy between pyramidal and nonpyramidal cells will enable us to characterize excitatory and inhibitory circuits that form the basis of auditory cortical networks. The proposed studies have the potential for delineating the cellular substrates that generate major functional features of auditory neocortex: isofrequency strips and binaural bands.
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