Role of Plasticity at Different Sites across the Time Course of Cerebellar Motor Learning

Abstract

Learning comprises multiple components that probably involve cellular and synaptic plasticity at multiple sites. Different neural sites may play their largest roles at different times during behavioral learning. We have used motor learning in smooth pursuit eye movements of monkeys to determine how and when different components of learning occur in a known cerebellar circuit. The earliest learning occurs when one climbing-fiber response to a learning instruction causes simple-spike firing rate of Purkinje cells in the floccular complex of the cerebellum to be depressed transiently at the time of the instruction on the next trial. Trial-over-trial depression and the associated learning in eye movement are forgotten in Ͻ6 s, but facilitate long-term behavioral learning over a time scale of ϳ5 min. During 100 repetitions of a learning instruction, simple-spike firing rate becomes progressively depressed in Purkinje cells that receive climbingfiber inputs from the instruction. In Purkinje cells that prefer the opposite direction of pursuit and therefore do not receive climbing-fiber inputs related to the instruction, simple-spike responses undergo potentiation, but more weakly and more slowly. Analysis of the relationship between the learned changes in simple-spike firing and learning in eye velocity suggests an orderly progression of plasticity: first on Purkinje cells with complex-spike (CS) responses to the instruction, later on Purkinje cells with CS responses to the opposite direction of instruction, and last in sites outside the cerebellar cortex. Climbing-fiber inputs appear to play a fast and primary, but nonexclusive, role in pursuit learning.

The Roles of the Olivocerebellar Pathway in Motor Learning and Motor Control. A Consensus Paper

“…These data suggest that motor timing itself also strengthens the learning process in this paradigm, because the complex spikes associated with the conditioned response emerge and develop during the training and are phase locked to the initiation of the conditioned response, consolidating the learning process [204, 214]. Future studies will have to reveal to what extent the differences in simple spike modulations during these two forms of climbing fiber dependent motor learning mainly reflect the zebrin-positive and zebrin-negative character of the modules involved, whether they are due to the inherently different temporal character of the tonically driven VOR adaptation and the phasically driven eyeblink conditioning trials (see also [42, 218] for suppression mechanisms in trial by trial learning in zebrin-positive zones), and/or whether they are related to the direction of movements involved [27, 214, 215]. …”

Temporal dynamics of cerebellar and motor cortex physiological processes during motor skill learning

“…Animal work has shown that this form of adaptive learning is mediated, in part, by long-term depression of parallel fiber-Purkinje cell synapse in cerebellar cortex3031. In humans, studies using transcranial magnetic stimulation (TMS) to assess the inhibitory tone the CB exerts over M1 (cerebellar inhibition, CBI) have described changes in cerebellar excitability during motor adaptation studies89.…”

Cerebellar–M1 Connectivity Changes Associated with Motor Learning Are Somatotopic Specific

“…This creates a mismatch between the predicted and actual sensory outcome of a movement, which drives error reduction in healthy individuals (Tseng et al, 2007;Shadmehr et al, 2010). The cerebellum is thought to be critical for learning error-based adaptation tasks (Martin et al, 1996;Diedrichsen et al, 2005;Chen et al, 2006) because patients with cerebellar degeneration show a marked impairment in such learning (Weiner et al, 1983;Martin et al, 1996;Smith and Shadmehr, 2005). In addition, acquisition of a visuomotor adaptation is enhanced when anodal transcranial direct current stimulation, a form of noninvasive excitatory stimulation, is applied over the cerebellum during training (Galea et al, 2011;Block and Celnik, 2013).…”

“…Because this type of learning can transfer to untrained limbs (Sainburg and Wang, 2002;Criscimagna-Hemminger et al, 2003;Wang and Sainburg, 2004;Morton and Bastian, 2006;Savin and Morton, 2008;Balitsky Thompson and Henriques, 2010;Joiner et al, 2013), modulation of CBI in an untrained limb could be related to interlimb transfer (i.e., reflecting a somatotopy-specific plastic mechanism) or it could be a nonspecific response. Therefore, we also investigated CBI in the context of movement preparation in the absence of motor learning.…”