Cortical inhibitory network selects cerebellar signals for movement initiation

The onset of voluntary movements is driven by coordinated firing across a large population of motor cortical neurons. This pattern of activity is determined by both local interactions and long-range corticocortical and subcortical inputs. The way remote areas of the brain communicate to effectively drive movement is still unclear. We addressed this question by studying an important pathway through which the cerebellum communicates, via the motor thalamus, with the motor cortex. We found that similar to the sensory cortices, thalamic input to the motor cortex triggers feedforward inhibition by directly contacting inhibitory cells via particularly effective GluR2- lacking AMPA receptors blocked by NASPM. Based on these results, we constructed a classifier for SCP-responsive cortical cells to identify pyramidal and PV interneurons and study their role in controlling movements. The findings indicate that PV and pyramidal cells are co-driven by TC input in response to activation of the CTC pathway. During task performance, PV and pyramidal cells had comparable relations to movement parameters (directional tuning and movement duration). However, PV interneurons exhibited stronger movement-related activity that preceded the firing of pyramidal cells. This seemingly counterintuitive sequence of events where inhibitory cells are recruited more strongly and before excitatory cells may in fact enhance the signal-to-noise ratio of cerebellar signals by suppressing other inputs and prioritizing the excitatory synchronized volley from the TC system which occurs at the right time to overcome the inhibitory signal. In this manner, the CTC system can shape cortical activity in a way that exceeds its sheer synaptic efficacy.