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

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Abstract
Striatal spiny-projection neurons (SPNs) integrate glutamatergic inputs from the motor cortex and thalamus with neuromodulatory signals to regulate motor output. In vivo Ca 2+ imaging has demonstrated that spatially overlapping ensembles of direct and indirect pathway SPNs (dSPNs, iSPNs) are co-active during spontaneous movement. This co-activity is statistically greater among nearby neurons, correlates with behavioral state, and changes in an SPN-type-specific manner under pathological conditions. How this co-activity arises and whether it is important for movement are not well understood. Co-activity likely arises from shared excitatory inputs, the strength of which are scaled by well-characterized mechanisms of synaptic plasticity. Here, we show that the Group I metabotropic glutamate receptor 5 (mGluR5), which regulates the strength of corticostriatal synapses, is a key mediator of behaviorally relevant SPN co-activity. Pharmacological modulation of mGluR5 signaling bidirectionally altered movement and co-activity, but not the absolute level of activity in dSPNs. Targeted deletion of mGluR5 in dSPNs recapitulated the effects on spatiotemporal neural dynamics and movement, consistent with a striatum-specific effect of mGluR5 modulation. Targeted deletion of mGluR5 also produced changes in the synaptic properties of dSPNs. Separate from any effects on overall activity, our results show that excitatory synaptic modulation influences motor function by coordinating the spatial co-activation of dSPNs in vivo.
Funding Information
  • National Institute of Mental Health (R01MH099114)

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