Synaptic mechanisms modulate the spatiotemporal dynamics of striatal direct pathway neurons and motor output

Striatal spiny-projection neurons (SPNs) integrate glutamatergic inputs from the motor cortex and thalamus with neuromodulatory signals to regulate motor output.In vivoCa²⁺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, we show that the Group I metabotropic glutamate receptor 5 (mGluR5), which regulates synaptic strength at corticostriatal synapses, is a key mediator of spatially clustered SPN co-activity. Pharmacological modulation of mGluR5 signaling bidirectionally altered movement and spatially clustered dynamics, but not the absolute level of activity of dSPNs. Targeted deletion of mGluR5 in dSPNs recapitulated the effects on spatiotemporal neural dynamics and movement demonstrating a striatum-specific effect of mGluR5. Targeted deletion of mGluR5 also produced changes in the synaptic properties of dSPNs. These results show that properties of excitatory synapses influence motor function by shaping the characteristic spatially clustered patterns of co-activity that typify dSPN activationin vivo.