bioRxiv ScienceSearch

Biology subjects

Israel, Z.

Publications and source records attributed to Israel, Z..

2 recordsLinked to original sources

Reversible block of cerebellar outflow reveals cortical circuitry for motor coordination

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.\n\nHIGHLIGHTSO_LIHigh frequency stimulation blocked cerebellar outflow and impaired motor behavior\nC_LIO_LIResponse patterns and coordinated firing of CTC neurons were disrupted\nC_LIO_LIThe spatial tuning and early preparatory activity of neurons were unaffected\nC_LIO_LICerebellar control of local and global cortical synchrony supports motor timing\nC_LI\n\nIN BRIEFNashef 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.

neuroscience

Human Subthalamic Nucleus Selectively Decreases its Response to the Go-Signal in a Motor Inhibition Context

To better understand the mechanism of movement facilitation and inhibition in the subthalamic nucleus (STN), we recorded subthalamic multiunit activity intra-operatively while parkinsonian patients (n=43 patients, 173 sites) performed increasingly complex oddball paradigms: auditory ( None-Go, n=7, 28), simple movement ( All-Go, n=7, 26) and movement inhibition ( Go-NoGo, n=29, 119) tasks. To enable physiological sampling of the different subthalamic nucleus domains in both hemispheres, each patient performed one of the oddball paradigms several times.\n\nThe human STN responded mainly to movement-involving tasks: movement execution at the motor STN and movement planning at the limbic-associative STN. In the limbic-associative STN, responses to the inhibitory cue (deviant tone) in the movement inhibition task were not significantly different from the simple movement task. However, responses to the go cue (frequent tone) were significantly reduced. The reduction was mainly in the negative component of the evoked response amplitude. Successful movement inhibition was correlated with higher baseline activity before the inhibitory cue.\n\nWe suggest that the STN adapts to movement inhibition context by selectively decreasing the amplitude of neuronal activity. Thus, the STN enables movement inhibition not by increasing responses to the inhibitory cue but by reducing responses to the release cue. The negative component of the evoked response probably facilitates movement and a higher baseline activity enables successful inhibition of movement. These discharge modulations were found in the ventromedial, non-motor domain of the STN and therefore suggest a significant role of the associative-limbic domains in movement planning and in global movement regulation.

neuroscience