Motor feedback control of layer six circuits

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PROJECT SUMMARY The neocortex is essential for movement, sensation, and higher cognitive functions. A key organization feature of the cortex is that it comprises several distinct areas that are interconnected by long-range corticocortical pathways. These direct corticocortical connections are generally thought to mediate cognitive processes like attention, prediction, and awareness. Dysfunction in corticocortical connectivity has been associated with certain neurological disorders like autism, epilepsy, and schizophrenia. Long-range corticocortical connections link hierarchically organized cortical areas. For example, lower-order cortical areas such as sensory cortices communicate sensory receptive field information to higher-order areas via feedforward pathways (FF). In contrast, higher-order cortical areas send feedback projections (FB) to lower-order areas and are thought to modulate the responsiveness of their target cells. Recent work suggests that local GABAergic interneurons play a critical role in cortical feedback modulation. Although much is known about the FB recruitment of inhibitory circuits in superficial layers (layer 2/3), the underlying inhibitory circuits involved in FB modulation in deep layers (layer 5/6) are unknown. Indeed, previous anatomical and physiological studies strongly suggest that IN populations are distinct between superficial and deep layers of the cortex, suggesting that different inhibitory circuits could be involved in cortical feedback circuits. This proposal will investigate the inhibitory networks mediated motor integration in layer 6 of the mouse somatosensory cortex. There are three specific aims in this proposal: 1) Characterize layer 6 inhibitory cell types recruited by vM1 input; 2) Determine what different subtypes of L6 excitatory cells are activated by vM1 input; 3) Determine the functions of vM1 evoked FFI to excitatory cells in L6. To address these aims, I will use an array of in vitro electrophysiological techniques combined with various optogenetics approaches, transgenic mouse lines, and histological methods to identify the inhibitory circuits mediating motor integration in L6 of the somatosensory cortex. Ultimately, these findings will advance our fundamental understanding of corticocortical connectivity and how the motor cortex influences processing in the sensory cortex. Such information will be necessary for understanding certain neuropsychiatric disorders involving corticocortical communication.