Biology subjects

Nashef, A.

Publications and source records attributed to Nashef, A..

4 recordsLinked to original sources

bioRxiv2023

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.

neuroscience↗

bioRxiv2020

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.

neuroscience↗

bioRxiv2020

Motor cortical plasticity in response to skill acquisition in adult monkeys

Cortical maps often undergo plastic changes during learning or in response to injury. In sensory areas, these changes are thought to be triggered by alterations in the pattern of converging inputs and a functional reassignment of the deprived cortical region. In the motor cortex, training on a task that engages distal effectors was shown to increase their cortical representation (as measured by response to intracortical microstimulation). However, this expansion could be a specific outcome of using a demanding dexterous task. We addressed this question by measuring the long-term changes in cortical maps of monkeys that were sequentially trained on two different tasks involving either proximal or distal joints. We found that motor cortical remodeling in adult monkeys was symmetric such that both distal and proximal movements can comparably alter motor maps in a fully reversible manner according to task demands. Further, we found that the change in mapping often included a switch between remote joints (e.g., a finger site switched to a shoulder site) and reflected a usage-consistent reorganization of the map rather than the local expansion of one representation into nearby sites. Finally, although cortical maps were considerably affected by the performed task, motor cortical neurons throughout the motor cortex were equally likely to fire in a task-related manner independent of the task and/or the recording site. These results may imply that in the motor system, enhanced motor efficiency is achieved through a dynamical allocation of larger cortical areas and not by specific recruitment of task-relevant cells.

neuroscience↗

bioRxiv2018

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↗