Grant: Discovery Grants Program - Individual

Dexterous forelimb movements like reaching, grasping, and manipulating objects are core components of the diverse behavioral repertoire of many mammals, including rodents. These behaviors are essential for interacting with the environment and the precision with which arms, hands and digits can be moved represent one of the most impressive feats of the mammalian motor system. The ability to perform such dexterous forelimb movements arises from the dynamic and continuous refinement of motor outputs by sensory feedback, otherwise known as sensorimotor integration. It is through sensorimotor integration that the motor system can incorporate sensory information about one's body and the external environment to inform and optimally shape motor output. Despite the critical contribution of sensory inputs to the performance of dexterous forelimb movements, most studies investigate the motor aspect of such movements in isolation, with little to no consideration for the role of sensory feedback. As such, little is known about the interregional circuits underlying sensorimotor integration and the mechanisms through which sensory and motor regions of the nervous system interact to produce dexterous forelimb movements. The goal of this research program is to investigate the neural basis of sensorimotor integration by exploring the anatomical and functional organization of the various neural circuits linking sensory and motor regions of the brain in the context of dexterous forelimb movements. Previously, we have shown that two sensory nuclei of the thalamus, the ventral-posterior nucleus (VP) and the posterior thalamic nucleus (PO), which receive direct somatosensory inputs from the periphery, send particularly abundant projections to the forelimb primary motor cortex (fM1); the main cortical area involved in the production of dexterous forelimb movements. To begin our dissection of the circuitry underlying sensorimotor integration for dexterous behavior, we will further explore these two thalamocortical circuits. First, we will provide a comprehensive anatomical description of the postsynaptic targets of VP and PO in fM1 using transsynaptic anterograde tracers. Next, we will perform electrophysiological experiments to reveal how fM1 neurons functionally integrate the inputs from VP and PO. Then, we will perturb the circuits linking VP and PO to fM1 in awake behaving animals with chemogenetics to determine their contribution to dexterous forelimb movements. Taken together, these experiments will yield novel insights into the fine-scale anatomical and functional logic of circuits linking sensory and motor regions of the brain and reveal how they help orchestrate dexterous behaviors. In addition to providing a better comprehension of the sensorimotor system, our work may help develop bio-inspired sensorimotor control strategies for robotic systems and may lay the foundation for a better understanding of sensorimotor deficits caused by motor disease or injury.