Modulation of the spatiotemporal dynamics of striatal direct pathway neurons and motor output by mGluR5

Abstract

AbstractStriatal spiny projection neurons (SPNs) integrate glutamatergic input from motor cortex and thalamus with various neuromodulatory signals to regulate motor output.In vivoCa2+imaging has demonstrated that spatially compact clusters of direct and indirect pathway SPNs (dSPNs and iSPNs) co-activate during spontaneous movement. This co-activity is statistically greater between neurons in close proximity, correlates with the animal’s behavioral state, and could, in part, reflect shared excitatory inputs. However, whether and how synaptic mechanism have a role in generating this distinctive spatiotemporal activity is unknown. Here, we show that the Group I metabotropic glutamate receptor 5 (mGluR5) plays a key role in the formation and regulation of spatially clustered SPN co-activity. Pharmacological modulation of mGluR5 signaling bidirectionally altered movement and spatially clustered dynamics, but not mean activity levels of dSPNs. Targeted deletion of mGluR5 in dSPNs recapitulated the effects on spatiotemporal neural dynamics and movement demonstrating a striatal specific effect of mGluR5. These changes in locomotion and neural ensemble dynamics were also correlated with changes in dSPNs synaptic properties in the cKO mice. Together results suggest excitatory synaptic function influences motor function by shaping the characteristic spatially clustered patterns of co-activity that typify dSPN activationin vivo.