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Reevaluating the ability of cerebellum in associative motor learning.

ABSTRACT: It has been well established that the cerebellum and its associated circuitry constitute the essential neuronal system for both delay and trace classical eyeblink conditioning (DEC and TEC). However, whether the cerebellum is sufficient to independently modulate the DEC, and TEC with a shorter trace interval remained controversial. Here, we used direct optogenetic stimulation of mossy fibers in the middle cerebellar peduncle (MCP) as a conditioned stimulus (CS) replacement for the peripheral CS (eg, a tone CS or a light CS) paired with a periorbital shock unconditioned stimulus (US) to examine the ability of the cerebellum to learn the DEC and the TEC with various trace intervals. Moreover, neural inputs to the pontine nucleus (PN) were pharmacological blocked to limit the associative motor learning inside the cerebellum. We show that all rats quickly acquired the DEC, indicating that direct optogenetic stimulation of mossy fibers in the left MCP is a very effective and sufficient CS to establish DEC and to limit the motor learning process inside the cerebellum. However, only five out of seven rats acquired the TEC with a 150-ms trace interval, three out of nine rats acquired the TEC with a 350-ms trace interval, and none of the rats acquired the TEC with a 500-ms trace interval. Moreover, pharmacological blocking glutamatergic and GABAergic inputs to the PN from the extra-cerebellar and cerebellar regions has no significant effect on the DEC and TEC learning with the optogenetic CS. These results indicate that the cerebellum has the ability to independently support both the simple DEC, and the TEC with a trace interval of 150 or 350?ms, but not the TEC with a trace interval of 500?ms. The present results are of great importance in our understanding of the mechanisms and ability of the cerebellum in associative motor learning and memory.

SUBMITTER: Li DB

PROVIDER: S-EPMC6465343 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Reevaluating the ability of cerebellum in associative motor learning.

Li Da-Bing DB Yao Juan J Sun Lin L Wu Bing B Li Xuan X Liu Shu-Lei SL Hou Jing-Ming JM Liu Hong-Liang HL Sui Jian-Feng JF Wu Guang-Yan GY

Scientific reports 20190415 1

It has been well established that the cerebellum and its associated circuitry constitute the essential neuronal system for both delay and trace classical eyeblink conditioning (DEC and TEC). However, whether the cerebellum is sufficient to independently modulate the DEC, and TEC with a shorter trace interval remained controversial. Here, we used direct optogenetic stimulation of mossy fibers in the middle cerebellar peduncle (MCP) as a conditioned stimulus (CS) replacement for the peripheral CS ...[more]

PMID: 30988338

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Project description:Previous motor learning studies based on adapting movements of the hemiparetic arm in stroke subjects have not accounted for spasticity occurring in specific joint ranges (spasticity zones), resulting in equivocal conclusions about learning capacity. We compared the ability of participants with stroke to rapidly adapt elbow extension movements to changing external load conditions outside and inside spasticity zones. Participants with stroke ( n = 12, aged 57.8 ± 9.6 yr) and healthy age-matched controls ( n = 8, 63.5 ± 9.1 yr) made rapid 40°-50° horizontal elbow extension movements from an initial (3°) to a final (6°) target. Sixteen blocks (6-10 trials/block) consisting of alternating loaded (30% maximal voluntary contraction) and nonloaded trials were made in one (controls) or two sessions (stroke; 1 wk apart). For the stroke group, the tonic stretch reflex threshold angle at which elbow flexors began to be activated during passive elbow extension was used to identify the beginning of the spasticity zone. The task was repeated in joint ranges that did or did not include the spasticity zone. Error correction strategies were identified by the angular positions before correction and compared between groups and sessions. Changes in load condition from no load to load and vice versa resulted in undershoot and overshoot errors, respectively. Stroke subjects corrected errors in 1-4 trials compared with 1-2 trials in controls. When movements did not include the spasticity zone, there was an immediate decrease in the number of trials needed to restore accuracy, suggesting that the capacity to learn may be preserved after stroke but masked by the presence of spasticity. NEW & NOTEWORTHY When arm movements were made outside, instead of inside, the range affected by spasticity, there was an immediate decrease in the number of trials needed to restore accuracy in response to a change in the external load. This suggests that motor learning processes may be preserved in patients with stroke but masked by the presence of spasticity in specific joint ranges. This has important implications for designing rehabilitation interventions predicated on motor learning principles.

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Reevaluating the ability of cerebellum in associative motor learning.

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Reevaluating the ability of cerebellum in associative motor learning.

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