Memory Consolidation in the Cerebellar Cortex

Abstract

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABAA agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage.

Modeling memory consolidation during posttraining periods in cerebellovestibular learning

“…In Pavlovian eyeblink conditioning, a conditioned response seems to be consolidated in the cerebellar cortex (29)(30)(31)(32). Even in OKR adaptation, a trace of long-term memory remains in the cerebellar cortex as the decrease in the number of PF-PC synapses (33,34), which might represent eye movement trajectory or information on OKR phase (35)(36)(37).…”

Classical conditioning of motor responses: What is the learning mechanism?

“…This conditioned response (CR) is abolished or severely impaired by lesioning or pharmacological inactivation of the cerebellum (McCormick, Clark, Lavond, & Thompson, 1982;Yeo, Hardiman, & Glickstein, 1984). Evidence from Yeo and collaborators show that pharmacological inactivation of the cerebellar cortex prevents consolidation of the learning, suggesting that the cortex is the main locus of memory storage (Attwell, Cooke, & Yeo, 2002;Kellett, Fukunaga, Chen-Kubota, Dean, & Yeo, 2010). However, in spite of intensive research the synaptic mechanisms involved have remained unclear.…”

Role of Cerebellar Cortical Protein Synthesis in Transfer of Memory Trace of Cerebellum-Dependent Motor Learning

“…In mice in which feedforward inhibitory inputs to Purkinje cells are removed genetically, the transfer of memory trace of HVOR adaptation is specifically impaired (Wulff et al, 2009). In rabbit eyeblink conditioning, the consolidation of conditioned responses is inhibited by tem- poral inactivation of the cerebellar cortex by muscimol infusion immediately following each training session, whereas the inactivation of cerebellar nuclei after training induced no inhibitory effect (Attwell et al, 2002;Cooke et al, 2004;Kellett et al, 2010).…”