Intrastriatal inhibition of extracellular signal-regulated kinases impaired the consolidation phase of motor skill learning

Abstract

It is well known that motor skill learning is characterized by rapid improvement in performances within the first training session and a slower progression in the following sessions that is correlated to the consolidation phase. Our goal was to establish the regional mapping of neural activity in relation to the motor skill learning included in the accelerating rotarod task using Zif268, c-Fos and ERK 1/2. As ERK 1/2 activity is also a marker of adaptive response to synaptic activation for newly learned events, its role was also verified. Learning the rotarod task did not affect levels of Zif268, but induced a selective upregulation of c-Fos in the cerebellum, motor cortex M1 and M2, cingulate cortex CG1 and CG2 as well as dorsal striatum. Notably, levels of phosphorylated ERK 1/2 were selectively increased in this later region during consolidation phase. To further study this effect, we injected inhibitors of ERK activation, the SL327 intraperitoneally or the PD98059 directly into the dorsal striatum, and observed that motor performances were exclusively impaired in this phase. These findings indicate that ERK 1/2 activity of the dorsal striatum is critical for the consolidation of late but not early phase of motor skill memory.