Quantitative Proteomics Reveals Distinct Molecular Signatures of Different Cerebellum-Dependent Learning Paradigms

The
cerebellum improves motor performance by adjusting motor gain
appropriately. As de novo protein synthesis is essential for the formation
and retention of memories, we hypothesized that motor learning in
the opposite direction would induce a distinct pattern of protein
expression in the cerebellum. We conducted quantitative proteomic
profiling to compare the level of protein expression in the cerebellum
at 1 and 24 h after training from mice that underwent different paradigms
of cerebellum-dependent oculomotor learning from specific directional
changes in motor gain. We quantified a total of 43 proteins that were
significantly regulated in each of the three learning paradigms in
the cerebellum at 1 and 24 h after learning. In addition, functional
enrichment analysis identified protein groups that were differentially
enriched or depleted in the cerebellum at 24 h after the three oculomotor
learnings, suggesting that distinct biological pathways may be engaged
in the formation of three oculomotor memories. Weighted correlation
network analysis discovered groups of proteins significantly correlated
with oculomotor memory. Finally, four proteins (Snca, Sncb, Cttn,
and Stmn1) from the protein group correlated with the learning amount
after oculomotor training were validated by Western blot. This study
provides a comprehensive and unbiased list of proteins related to
three cerebellum-dependent motor learning paradigms, suggesting the
distinct nature of protein expression in the cerebellum for each learning
paradigm. The proteomics data have been deposited to the ProteomeXchange
Consortium with identifiers .