A dual Purkinje cell rate and synchrony code sculpts reach kinematics.

Cerebellar Purkinje cells (PCs) encode movement kinematics in their population firing rates. Firing rate suppression is hypothesized to disinhibit neurons in the cerebellar nuclei, promoting adaptive movement adjustments. Debates persist, however, about whether a second disinhibitory mechanism, PC simple spike synchrony, is a relevant population code. We addressed this question by relating PC rate and synchrony patterns recorded with high density probes, to mouse reach kinematics. We discovered behavioral correlates of PC synchrony that align with a known causal relationship between activity in cerebellar output. Reach deceleration was positively correlated with both Purkinje firing rate decreases and synchrony, consistent with both mechanisms disinhibiting target neurons, which are known to adjust reach velocity. Direct tests of the contribution of each coding scheme to nuclear firing using dynamic clamp, combining physiological rate and synchrony patterns ex vivo, confirmed that physiological levels of PC simple spike synchrony are highly facilitatory for nuclear firing. These findings suggest that PC firing rate and synchrony collaborate to exert fine control of movement.

A cerebellar origin of feedforward inhibition to the motor cortex in non-human primates.

Voluntary movements are driven by coordinated activity across a large population of motor cortical neurons. Formation of this activity is controlled by local interactions and long-range inputs. How remote areas of the brain communicate with motor cortical neurons to effectively drive movement remains unclear. We address this question by studying the cerebellar-thalamocortical system. We find that thalamic input to the motor cortex triggers feedforward inhibition by contacting inhibitory cells via highly effective GluR2-lacking AMPA receptors and that, during task performance, the activity of parvalbumin (PV) and pyramidal cells exhibits relations comparable with movement parameters. We also find that the movement-related activity of PV interneurons precedes firing of pyramidal cells. This counterintuitive sequence of events, where inhibitory cells are recruited more strongly and before excitatory cells, may amplify the cortical effect of cerebellar signals in a way that exceeds their sheer synaptic efficacy by suppressing other inputs.

Area-specific thalamocortical synchronization underlies the transition from motor planning to execution.

We studied correlated firing between motor thalamic and cortical cells in monkeys performing a delayed-response reaching task. Simultaneous recording of thalamocortical activity revealed that around movement onset, thalamic cells were positively correlated with cell activity in the primary motor cortex but negatively correlated with the activity of the premotor cortex. The differences in the correlation contrasted with the average neural responses, which were similar in all three areas. Neuronal correlations reveal functional cooperation and opposition between the motor thalamus and distinct motor cortical areas with specific roles in planning vs. performing movements. Thus, by enhancing and suppressing motor and premotor firing, the motor thalamus can facilitate the transition from a motor plan to execution.

Reversible Block of Cerebellar Outflow Reveals Cortical Circuitry for Motor Coordination.

Coordinated movements are achieved by well-timed activation of selected muscles. This process relies on intact cerebellar circuitry, as demonstrated by motor impairments following cerebellar lesions. Based on anatomical connectivity and symptoms observed in cerebellar patients, we hypothesized that cerebellar dysfunction should disrupt the temporal patterns of motor cortical activity, but not the selected motor plan. To test this hypothesis, we reversibly blocked cerebellar outflow in primates while monitoring motor behavior and neural activity. This manipulation replicated the impaired motor timing and coordination characteristic of cerebellar ataxia. We found extensive changes in motor cortical activity, including loss of response transients at movement onset and decoupling of task-related activity. Nonetheless, the spatial tuning of cells was unaffected, and their early preparatory activity was mostly intact. These results indicate that the timing of actions, but not the selection of muscles, is regulated through cerebellar control of motor cortical activity.

Cerebellar Shaping of Motor Cortical Firing Is Correlated with Timing of Motor Actions.

In higher mammals, motor timing is considered to be dictated by cerebellar control of motor cortical activity, relayed through the cerebellar-thalamo-cortical (CTC) system. Nonetheless, the way cerebellar information is integrated with motor cortical commands and affects their temporal properties remains unclear. To address this issue, we activated the CTC system in primates and found that it efficiently recruits motor cortical cells; however, the cortical response was dominated by prolonged inhibition that imposed a directional activation across the motor cortex. During task performance, cortical cells that integrated CTC information fired synchronous bursts at movement onset. These cells expressed a stronger correlation with reaction time than non-CTC cells. Thus, the excitation-inhibition interplay triggered by the CTC system facilitates transient recruitment of a cortical subnetwork at movement onset. The CTC system may shape neural firing to produce the required profile to initiate movements and thus plays a pivotal role in timing motor actions.

Area-specific processing of cerebellar-thalamo-cortical information in primates.

The cerebellar-thalamo-cortical (CTC) system plays a major role in controlling timing and coordination of voluntary movements. However, the functional impact of this system on motor cortical sites has not been documented in a systematic manner. We addressed this question by implanting a chronic stimulating electrode in the superior cerebellar peduncle (SCP) and recording evoked multiunit activity (MUA) and the local field potential (LFP) in the primary motor cortex ([Formula: see text]), the premotor cortex ([Formula: see text]) and the somatosensory cortex ([Formula: see text]). The area-dependent response properties were estimated using the MUA response shape (quantified by decomposing into principal components) and the time-dependent frequency content of the evoked LFP. Each of these signals alone enabled good classification between the somatosensory and motor sites. Good classification between the primary motor and premotor areas could only be achieved when combining features from both signal types. Topographical single-site representation of the predicted class showed good recovery of functional organization. Finally, the probability for misclassification had a broad topographical organization. Despite the area-specific response features to SCP stimulation, there was considerable site-to-site variation in responses, specifically within the motor cortical areas. This indicates a substantial SCP impact on both the primary motor and premotor cortex. Given the documented involvement of these cortical areas in preparation and execution of movement, this result may suggest a CTC contribution to both motor execution and motor preparation. The stimulation responses in the somatosensory cortex were sparser and weaker. However, a functional role of the CTC system in somatosensory computation must be taken into consideration.