Master’s Thesis in Molecular Medical Biology

Fine motor skills are learned through repetitive practice and once learned, last for a long time. Skilled reaching is linked to structural and functional changes in multiple brain regions including, in particular, the primary motor cortex. Previous studies demonstrated that fine motor skill learning is associated with cortical synaptogenesis and motor map reorganization. At present, studies have implicated an indispensable role of epigenetic alterations in both hippocampal-and striatal-dependent memory formations, while examinations into the epigenetic changes in the primary motor cortex are lacking. The current study was aimed to identify epigenetic changes in motor cortex as a result of extensive motor skill learning using the single pellet skilled reaching task. Male Wistar rats were trained in the single pellet skilled reaching task (n = 6) for 10 consecutive days or were, under similar conditions, given access to pellets that did not require skilled reaches (n = 6). Skilled motor trained rats exhibited a rapid increase in successful reaches during the first four days of motor training before reaching a plateau, indicative of the acquisition and consolidation of the learned task, respectively. Expression profiles of chromatin modifying enzymes were screened using epigenetic-targeted PCR arrays. Results suggest that gene expression levels of multiple chromatin regulatory enzymes were down-regulated in the motor cortex of trained animals compared to controls following 10 days of motor training in the skilled reaching task. Among the chromatin modifying enzymes, the transcription level of Smyd1 (SET and MYND domain containing 1; NM_001106595) was lower (-2.17 fold-change) in motor cortex after 10 days of training compared to controls. Our results point to an epigenetic regulation of chromatin modification markers in the primary motor cortex that possibly underlie the mechanisms of synaptic plasticity, synaptogenesis and the formation of procedural memory.