A cerebellar-thalamocortical pathway drives behavioral context-dependent movement initiation

Dacre, Joshua; Colligan, Matt; Clarke, Thomas; Ammer, Julian; Schiemann, Julia; Chamosa-Pino, Victor; Claudi, Federico; Harston, J. Alex; Eleftheriou, Constantinos; Pakan, Janelle M.P.; Huang, Cheng-Chiu; Hantman, Adam W.; Rochefort, Nathalie L.; Duguid, Ian

doi:10.1016/j.neuron.2021.05.016

Cited by 74 publications

(88 citation statements)

References 111 publications

(179 reference statements)

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“…For example, VL neurons can selectively respond to movements that are self-or othergenerated (Butler et al, 1992a;Butler et al, 1992b), with the activity of neurons responsive to self-generated movements being too fast to be sensory (Bosch-Bouju et al, 2014;Gaidica et al, 2018). Other studies suggest that VL can influence the production of movement via its projections to M1 (Dacre et al, 2021;Sauerbrei et al, 2020). Here, at P12 and P16, most VL neurons were classified as sensory (Fig.…”

Section: Divergent Representations Of Movement In Vp and Vlmentioning

confidence: 84%

“…In primates, VL neurons respond faster than VP neurons to self-generated-but not other-generated-movements (Butler et al, 1992a;Butler et al, 1992b). In rodents, VL shows rapid movement-related activity, although the timing of this activity has not been directly compared to sensory responses in VP (Bosch-Bouju et al, 2014;Dacre et al, 2021;Gaidica et al, 2018;Sauerbrei et al, 2020).…”

Section: Why Twitches?mentioning

confidence: 99%

“…reaching for food), directly attributing neural activity in VL to any one facet of the movement has been challenging. Further complicating this issue, cerebellar inactivation can change the kinematics of the movements themselves (Becker and Person, 2019;Dacre et al, 2021;Nashef et al, 2019). Thus, although the cerebellum clearly shapes movement-related activity in VL, fully characterizing the cerebellum's contribution to this activity has remained elusive.…”

Section: Why Twitches?mentioning

confidence: 99%

“…This coordination is made possible by the production of copies of motor commands (or corollary discharges) that contribute to the computation of a forward model in the cerebellum and other structures, providing the animal with an internal representation of its own movements (Bastian, 2006;Crapse and Sommer, 2008;Franklin and Wolpert, 2011;Hull, 2020). One of the major targets of the cerebellum is the motor thalamus-the ventral lateral nucleus (VL)-which projects to primary motor cortex (M1; Bosch-Bouju et al, 2013;Dacre et al, 2021;Gornati et al, 2018;Habas et al, 2019;Sauerbrei et al, 2020;Wolpert et al, 1998). In its entirety, this system enables flexible and adaptive updating of movements in real time.…”

Section: Introductionmentioning

confidence: 99%

“…To understand how internal representations of movement in the cerebellum contribute to behavior, researchers have assessed either learning-related changes in cerebellar activity as an animal learns a novel behavioral task (Bosch-Bouju et al, 2014;Gaidica et al, 2018;Wagner et al, 2019) or the behavioral consequences of manipulating the cerebellothalamic system (Dacre et al, 2021;Nashef et al, 2019;Sauerbrei et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Developmental onset of a cerebellar-dependent forward model of movement in motor thalamus

Dooley

Sokoloff

Blumberg

2021

Preprint

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To execute complex behavior with temporal precision, adult animals use internal models to predict the sensory consequences of self-generated movement. Here, taking advantage of the unique kinematic features of twitches-the brief, discrete movements of active sleep-we captured the developmental onset of a cerebellar-dependent internal model. Using rats at postnatal days (P) 12, P16, and P20, we compared neural activity in two thalamic structures: the ventral posterior (VP) and ventral lateral (VL) nuclei, both of which receive somatosensory input but only the latter of which receives cerebellar input. At all ages, twitch-related activity in VP lagged behind movement, consistent with sensory processing; similar activity was observed in VL through P16. At P20, however, VL activity precisely mimicked the twitch itself, a pattern of activity that depended on cerebellar input. Altogether, these findings implicate twitches in the development and refinement of internal models of movement.

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Section: Divergent Representations Of Movement In Vp and Vlmentioning

confidence: 84%

Section: Why Twitches?mentioning

confidence: 99%

Section: Why Twitches?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Developmental onset of a cerebellar-dependent forward model of movement in motor thalamus

Dooley

Sokoloff

Blumberg

2021

Preprint

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Limb Preference Changes after Focused‐Ultrasound Thalamotomy for Tremor

et al. 2023

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Background Magnetic resonance‐guided focused‐ultrasound (MRgFUS) thalamotomy is an effective treatment for essential and other tremors. It targets the ventrointermedius (Vim) nucleus, which is the thalamic relay in a proprioceptive pathway, and contains kinesthetic cells. Although MRgFUS thalamotomy reduces some risks associated with more invasive surgeries, it still has side effects, such as balance and gait disturbances; these may be caused by the lesion impacting proprioception. Objectives Our aim was to quantitatively measure the effects of MRgFUS on proprioception and limb use in essential tremor patients. We hypothesized that this thalamotomy alters proprioception, because the sensorimotor Vim thalamus is lesioned. Methods Proprioception was measured using the Kinarm exoskeleton robot in 18 patients. Data were collected pre‐operatively, and then 1 day, 3 months, and 1 year after surgery. Patients completed four tasks, assessing motor coordination and postural control, goal‐directed movement and bimanual planning, position sense, and kinesthesia. Results Immediately after surgery there were changes in posture speed (indicating tremor improvement), and in bimanual hand use, with the untreated limb being preferred. However, these measures returned to pre‐operative baseline over time. There were no changes in parameters related to proprioception. None of these measures correlated with lesion size or lesion‐overlap with the dentato‐rubro‐thalamic tract. Conclusions This is the first quantitative assessment of proprioception and limb preference following MRgFUS thalamotomy. Our results suggest that focused‐ultrasound lesioning of the Vim thalamus does not degrade proprioception but alters limb preference. This change may indicate a required “relearning” in the treated limb, because the effect is transient. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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