Cerebellar inactivation impairs memory of learned prism gaze-reach calibrations

Abstract

Three monkeys performed a visually guided reach-touch task with and without laterally displacing prisms. The prisms offset the normally aligned gaze/reach and subsequent touch. Naive monkeys showed adaptation, such that on repeated prism trials the gaze-reach angle widened and touches hit nearer the target. On the first subsequent no-prism trial the monkeys exhibited an aftereffect, such that the widened gaze-reach angle persisted and touches missed the target in the direction opposite that of initial prism-induced error. After 20-30 days of training, monkeys showed long-term learning and storage of the prism gaze-reach calibration: they switched between prism and no-prism and touched the target on the first trials without adaptation or aftereffect. Injections of lidocaine into posterolateral cerebellar cortex or muscimol or lidocaine into dentate nucleus temporarily inactivated these structures. Immediately after injections into cortex or dentate, reaches were displaced in the direction of prism-displaced gaze, but no-prism reaches were relatively unimpaired. There was little or no adaptation on the day of injection. On days after injection, there was no adaptation and both prism and no-prism reaches were horizontally, and often vertically, displaced. A single permanent lesion (kainic acid) in the lateral dentate nucleus of one monkey immediately impaired only the learned prism gaze-reach calibration and in subsequent days disrupted both learning and performance. This effect persisted for the 18 days of observation, with little or no adaptation.

Modulation of error-sensitivity during a prism adaptation task in people with cerebellar degeneration

“…The present results expand previous findings by suggesting that Purkinje cell dysfunction leads to impairments in prism adaptation in humans. The results also agree with nonhuman studies that reported impairments in prism adaptation in response to abrupt introduction of visual displacement after lesions in the cerebellar cortex (Baizer et al 1999;Norris et al 2011). Our critical observation was that performance of the patients benefited from the gradual protocol.…”

Genetic silencing of olivocerebellar synapses causes dystonia-like behaviour in mice

“…The inactivation would be different since lidocaine blocks additional cellular components. However, at the behavioural level, lidocaine and muscimol injections into the cerebellar nuclei produce similar consequences676869. This equivalence likely exists because blocking the output of the nuclei determines the behavioural outcome, and therefore inhibiting passing axons has little consequence because they eventually feed into the nuclei that are blocked.…”

Taking Aim at the Cognitive Side of Learning in Sensorimotor Adaptation Tasks

“…Inspired by its unique anatomy and physiology, detailed models of cerebellar learning [71–74] have been developed and refined, using tasks that involve adaptation of eye movement reflexes [51,75]. In terms of reaching studies, patients with cerebellar degeneration consistently show attenuated adaptation in response to sensory perturbations [14,15,36,47,76]. Furthermore, cerebellar activity is correlated with sensory prediction errors, the putative signal for sensorimotor recalibration [77].…”