UC San Diego

Appropriate patterning of synaptic circuitry is vital for proper central nervous system function, and neurons retain a significant capacity for synaptic reorganization throughout life. To better understand how synaptic alterations mediate the development and refinement of complex behavior, this dissertation investigates the neurophysiological and circuit-level changes accompanying 1) the emergence of fine motor behavior during development, and 2) motor skill learning in adulthood. We developed methods for identifying individual neurons of the motor cortex that are associated with specific motor domains to enable study of synaptic modifications among neural subpopulations associated with discrete behaviors. This was accomplished by labeling individual corticospinal motor neurons of layer V motor cortex that are associated with either proximal or distal forelimb control, in the same animal. By way of thousands of paired whole-cell recordings, we find that the emergence of fine motor behavior is associated with a developmental switch in connection strategy and intrinsic cell properties, which fundamentally alter the manner by which excitation is spread within the corticospinal system in rats during development. These changes parallel the emergence of fine motor behavior, and may indeed be necessary for its expression. Motor skill learning in the adult rat is next discussed, where we find that task-related corticospinal neurons specifically increase excitatory interconnectivity, inhibitory input, and intrinsic excitability following skilled motor training. Neighboring corticospinal neurons not associated with the motor task, on the other hand, exhibit no changes in connectivity or neurophysiology. Such population-specific changes may enable local encoding of motor behavior, thus automating skilled motor execution and freeing up higher-order cognitive processes, such as attention, for other tasks. Furthermore, such learning- related changes are likely a ubiquitous feature of the neocortex and underlie numerous forms of cortical learning. In total, these findings identify, for the first time, neuronal properties of connectivity and synapse function that characterize the cortical underpinnings of complex behavior and the learning engram