Description:

John Marshall, PhD: Work-in-Progress Seminar Abstract

Striatal spiny-projection neurons (SPNs) integrate glutamatergic inputs from the motor cortex and thalamus with neuromodulatory signals to regulate motor output. In vivo Ca2+ imaging has demonstrated that ensembles of direct and indirect pathway SPNs (dSPNs, iSPNs) are coactive during spontaneous movement. Co-activity is statistically greater among nearby neurons, correlates with behavioral state, and undergoes plasticity in an SPN-type-specific manner under pathological conditions. This spatially clustered co-activity could reflect shared excitatory inputs. However, whether and how synaptic mechanisms generate this distinctive spatiotemporal activity is unknown. Here I will talk about two projects that aim to examine how synaptic mechanisms modulate the characteristic patterns of neural activity in the striatum. In one, I will show how pharmacological and genetic disruption of mGluR5 signaling, which regulates synaptic strength at corticostriatal synapses, alters spontaneous movement and dSPN spatiotemporal dynamics. And, I will talk about work that aims to track how synaptic strength at corticostriatal synapses is altered when animals must modify well established motor skills.