Grant: Project Grant

Humans learn and perform various motor skills that enable them to effectively function in the world, including communicating with each other, navigating the environment, and finding food and companions. Consequently, revealing how the nervous system regulates the performance and acquisition of motor skills is central to our understanding of behavior. Perineuronal nets (PNNs) are extracellular matrices that form around specific types of neurons and modulate brain activity and plasticity. To date, the synthesis and function of PNNs have been most extensively studied in brain areas that analyze sensory information, where PNNs have been found to stabilize the processing of sensory information and restrict plasticity in sensory circuits. However, despite that PNNs are abundant in brain areas that regulate motor function, very little is known about the role of PNNs in motor circuitry. To this end, we will investigate (a) how experiences that shape motor performance modulate the expression of PNNs in motor circuitry, (b) how manipulations of PNN expression in motor circuitry affect motor performance and learning, and (c) how various cell types in the brain regulate PNN expression. We hypothesize that the expression of PNNs in motor circuitry covaries with motor performance, stabilizes behavioral performance, restricts motor plasticity, and changes as a function of glia cells. These studies will not only provide fundamental insight into the neural mechanisms of behavioral performance and learning but will also impact our understanding of diseases that impair motor functioning (e.g., Parkinson's and Huntington's disease, ataxias). By integrating disparate research programs that examine the mechanisms of motor control and plasticity, our proposal will help generate novel treatments and interventions for motor dysfunctions.