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      Reversible block of cerebellar outflow reveals cortical circuitry for motor coordination

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      bioRxiv

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          SUMMARY

          Coordinated movements are achieved by selecting muscles and activating them at specific times. This process relies on intact cerebellar circuitry, as demonstrated by motor impairments triggered by 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 a loss of response transients at movement onset and a 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.

          HIGHLIGHTS

          • High frequency stimulation blocked cerebellar outflow and impaired motor behavior

          • Response patterns and coordinated firing of CTC neurons were disrupted

          • The spatial tuning and early preparatory activity of neurons were unaffected

          • Cerebellar control of local and global cortical synchrony supports motor timing

          IN BRIEF

          Nashef et al. used high frequency stimulation to block cerebellar outflow. This manipulation impaired motor timing and coordination similarly to symptoms found in cerebellar patients. In parallel, the response patterns of cortical neurons and cell-to-cell synchronization were altered, yet spatial tuning was maintained. Motor timing and coordination are regulated by a dedicated cerebellar signal that organizes execution-related activity of a motor cortical subnetwork.

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          Author and article information

          Journal
          bioRxiv
          September 28 2018
          Article
          10.1101/429043
          © 2018
          Product

          Molecular medicine, Neurosciences

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