@article {67338, title = {A cerebellar-thalamocortical pathway drives behavioral context-dependent movement initiation.}, journal = {Neuron}, volume = {109}, year = {2021}, month = {2021 Jun 15}, pages = {2326-2338}, abstract = {

Executing learned motor behaviors often requires the transformation of sensory cues into patterns of motor commands that generate appropriately timed actions. The cerebellum and thalamus are two key areas involved in shaping cortical output and movement, but the contribution of a cerebellar-thalamocortical pathway to voluntary movement initiation remains poorly understood. Here, we investigated how an auditory "go cue" transforms thalamocortical activity patterns and how these changes relate to movement initiation. Population responses in dentate/interpositus-recipient regions of motor thalamus reflect a time-locked increase in activity immediately prior to movement initiation that is temporally uncoupled from the go cue, indicative of a fixed-latency feedforward motor timing signal. Blocking cerebellar or motor thalamic output suppresses movement initiation, while stimulation triggers movements in a behavioral context-dependent manner. Our findings show how cerebellar output, via the thalamus, shapes cortical activity patterns necessary for learned context-dependent movement initiation.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2021.05.016}, author = {Dacre, Joshua and Colligan, Matt and Clarke, Thomas and Ammer, Julian J and Schiemann, Julia and Chamosa-Pino, Victor and Claudi, Federico and Harston, J Alex and Eleftheriou, Constantinos and Pakan, Janelle M P and Huang, Cheng-Chiu and Hantman, Adam W and Rochefort, Nathalie L and Duguid, Ian} } @article {65259, title = {Cortical pattern generation during dexterous movement is input-driven.}, journal = {Nature}, volume = {577}, year = {2020}, month = {2020 Jan 16}, pages = {386-91}, abstract = {

The motor cortex controls skilled arm movement by sending temporal patterns of activity to lower motor centres. Local cortical dynamics are thought to shape these patterns throughout movement execution. External inputs have been implicated in setting the initial state of the motor cortex, but they may also have a pattern-generating role. Here we dissect the contribution of local dynamics and inputs to cortical pattern generation during a prehension task in mice. Perturbing cortex to an aberrant state prevented movement initiation, but after the perturbation was released, cortex either bypassed the normal initial state and immediately generated the pattern that controls reaching or failed to generate this pattern. The difference in these two outcomes was probably a result of external inputs. We directly investigated the role of inputs by inactivating the thalamus; this perturbed cortical activity and disrupted limb kinematics at any stage of the movement. Activation of thalamocortical axon terminals at different frequencies disrupted cortical activity and arm movement in a graded manner. Simultaneous recordings revealed that both thalamic activity and the current state of cortex predicted changes in cortical activity. Thus, the pattern generator for dexterous arm movement is distributed across multiple, strongly interacting brain regions.

}, issn = {1476-4687}, doi = {10.1038/s41586-019-1869-9}, author = {Sauerbrei, Britton A and Guo, Jian-Zhong and Cohen, Jeremy D and Mischiati, Matteo and Guo, Wendy and Kabra, Mayank and Verma, Nakul and Mensh, Brett and Branson, Kristin and Hantman, Adam W} } @article {47277, title = {Cortex commands the performance of skilled movement.}, journal = {eLife}, volume = {4}, year = {2015}, month = {2015 Dec 3}, abstract = {

Mammalian cerebral cortex is accepted as being critical for voluntary motor control, but what functions depend on cortex is still unclear. Here we used rapid, reversible optogenetic inhibition to test the role of cortex during a head-fixed task in which mice reach, grab, and eat a food pellet. Sudden cortical inhibition blocked initiation or froze execution of this skilled prehension behavior, but left untrained forelimb movements unaffected. Unexpectedly, kinematically normal prehension occurred immediately after cortical inhibition even during rest periods lacking cue and pellet. This {\textquoteright}rebound{\textquoteright} prehension was only evoked in trained and food-deprived animals, suggesting that a motivation-gated motor engram sufficient to evoke prehension is activated at inhibition{\textquoteright}s end. These results demonstrate the necessity and sufficiency of cortical activity for enacting a learned skill.

}, issn = {2050-084X}, doi = {10.7554/eLife.10774}, author = {Guo, Jian-Zhong and Graves, Austin R and Guo, Wendy W and Zheng, Jihong and Lee, Allen and Rodr{\'\i}guez-Gonz{\'a}lez, Juan and Li, Nuo and Macklin, John J and Phillips, James W and Mensh, Brett D and Branson, Kristin and Hantman, Adam W} } @article {5893, title = {Convergence of pontine and proprioceptive streams onto multimodal cerebellar granule cells.}, journal = {eLife}, volume = {2}, year = {2013}, month = {2013 Feb 26}, pages = {e00400}, abstract = {

Cerebellar granule cells constitute the majority of neurons in the brain and are the primary conveyors of sensory and motor-related mossy fiber information to Purkinje cells. The functional capability of the cerebellum hinges on whether individual granule cells receive mossy fiber inputs from multiple precerebellar nuclei or are instead unimodal; this distinction is unresolved. Using cell-type-specific projection mapping with synaptic resolution, we observed the convergence of separate sensory (upper body proprioceptive) and basilar pontine pathways onto individual granule cells and mapped this convergence across cerebellar cortex. These findings inform the long-standing debate about the multimodality of mammalian granule cells and substantiate their associative capacity predicted in the Marr-Albus theory of cerebellar function. We also provide evidence that the convergent basilar pontine pathways carry corollary discharges from upper body motor cortical areas. Such merging of related corollary and sensory streams is a critical component of circuit models of predictive motor control. DOI:http://dx.doi.org/10.7554/eLife.00400.001.

}, issn = {2050-084X}, doi = {10.7554/eLife.00400}, author = {Huang, Cheng-Chiu and Sugino, Ken and Shima, Yasuyuki and Guo, Caiying and Bai, Suxia and Mensh, Brett D and Nelson, Sacha B and Hantman, Adam W} } @article {5896, title = {Clarke{\textquoteright}s column neurons as the focus of a corticospinal corollary circuit.}, journal = {Nature Neuroscience}, volume = {13}, year = {2010}, month = {2010 Oct}, pages = {1233-9}, abstract = {

Proprioceptive sensory signals inform the CNS of the consequences of motor acts, but effective motor planning involves internal neural systems capable of anticipating actual sensory feedback. Just where and how predictive systems exert their influence remains poorly understood. We explored the possibility that spinocerebellar neurons that convey proprioceptive sensory information also integrate information from cortical command systems. Analysis of the circuitry and physiology of identified dorsal spinocerebellar tract neurons in mouse spinal cord revealed distinct populations of Clarke{\textquoteright}s column neurons that received direct excitatory and/or indirect inhibitory inputs from descending corticospinal axons. The convergence of these descending inhibitory and excitatory inputs to Clarke{\textquoteright}s column neurons established local spinal circuits with the capacity to mark or modulate incoming proprioceptive input. Together, our genetic, anatomical and physiological results indicate that Clarke{\textquoteright}s column spinocerebellar neurons nucleate local spinal corollary circuits that are relevant to motor planning and evaluation.

}, keywords = {3-dione, 6-Cyano-7-nitroquinoxaline-2, Animals, beta-Galactosidase, Bicuculline, Cerebellum, Cholera Toxin, Electric Stimulation, Estrogen Antagonists, Excitatory Amino Acid Antagonists, Feedback, GABA Antagonists, Gene Expression Regulation, Glial Cell Line-Derived Neurotrophic Factor, Glycine Agents, Glycine Plasma Membrane Transport Proteins, Green Fluorescent Proteins, Homeodomain Proteins, Lysine, Membrane Potentials, Messenger, Mice, Models, Nerve Net, Neural Inhibition, Neural Pathways, Neurological, Newborn, Parvalbumins, Patch-Clamp Techniques, Protein Kinase C, RNA, Sensory, Sensory Receptor Cells, Spinal Cord, Stilbamidines, Strychnine, Tamoxifen, tau Proteins, Transcription Factors, Transgenic, Vesicular Glutamate Transport Protein 1}, issn = {1546-1726}, doi = {10.1038/nn.2637}, author = {Hantman, Adam W and Jessell, Thomas M} }