Synaptic integration of somatosensory and motor cortical inputs onto spiny projection neurons of mice caudoputamen

The basal ganglia play pivotal roles in motor control and cognitive functioning. These nuclei are embedded in an anatomical loop: cortex to basal ganglia to thalamus back to cortex. We focus here on an essential synapse for descending control, from cortical layer 5 (L5) onto the GABAergic spiny projection neurons (SPNs) of the caudoputamen (CP). We employed genetic labeling to distinguish L5 neurons from somatosensory (S1) and motor (M1) cortices in large volume serial electron microscopy and electrophysiology datasets to better detail these inputs. First, M1 and S1 synapses showed a strong preference to innervate the spines of SPNs and rarely contacted aspiny cells, which are likely to be interneurons. Second, L5 inputs commonly converge from both areas onto single SPNs. Third, compared to unlabeled terminals in CP, those labeled from M1 and S1 show ultrastructural hallmarks of strong driver synapses: They innervate larger spines that were more likely to contain a spine apparatus, more often had embedded mitochondria, and more often contacted multiple targets. Finally, these inputs also demonstrated driver-like functional properties: SPNs responded to optogenetic activation from S1 and M1 with large EPSP/Cs that depressed and were dependent on ionotropic but not metabotropic receptors. Together, our findings suggest that individual SPNs integrate driver input from multiple cortical areas with implications for how the basal ganglia relay cortical input to provide inhibitory innervation of motor thalamus.