We have discovered a select population of large GABAergic neurons at the layer IV-V border of rodent cerebral cortex which exhibits two distinguishing properties in the behaving animal. First, these cells are much more heavily labeled with 2-deoxyglucose (2DG) than any other cell population in the cortex. Second, within the whisker-defined context of the cortical barrel field, these neurons are activated both inside and outside columns corresponding to selectively stimulated whiskers; i.e. the cells exhibit """"""""ectopic"""""""" metabolic activation. This pattern of activation implies an integrative function or a battery of integrative functions for these inhibitory neurons. A likely possibility is that these cells provide """"""""tone"""""""" or gain control for the somatic cortex to hold activity in the feedforward excitatory pathway within the appropriate and interpretable dynamic range. We wish to test a number of specific hypotheses designed to clarify the functions and input/output relationships of these neurons. We will evaluate these hypotheses by making heavy use of our newly developed 2DG/immunostaining protocols. We will then use an extensive battery of CORE software routines to control the CORE B scanning microscope stage, to automatically generate montages of areas of interest from high-resolution images, and to automatically extract the labeled cells from high-resolution images. We will ablate specified combinations of whisker follicles at PND7 or in adults to eliminate specific whisker inputs without affecting the thalamocortical afferents, thereby selectively limiting the sensory inputs we have shown are necessary for normal intracortical axonal arbors. In this developmental context we will assess the pattern of 2DG labeling in the large GABAergic cells (hereafter referred to as E cells, for ectopic) in lower layer IV and upper layer V. In some experiments we will combine traditional tract-tracing methods with immunohistochemical methods and/or the 2DG protocols. We will isolate the effects of intracortical vs. thalamocortical inputs to the E cells by making lesions in layer IV or barrel cortex. Finally, we will analyze the synaptic inputs to E cells with the electron microscope.
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