Deep cerebellar nuclei inhibition by DREADDs modulates motor skill learning in mice

VARANI ANDRÉS P.; MAILHES-HAMON CAROLINE; YOUMIR RIHAM ; LÉNA CLÉMENT; POPA DANIELA

Congreso; 10th FENS Forum of Neuroscience; 2016

Clinical and preclinical studies demonstrate that the cerebellum is involved in motor skill learning. However, how cerebellar outputs could modulate this behavior remains unclear. Here, we investigated the effects of a specific and transient silencing in the neuronal activity of cerebellar outputs during motor skill learning in mice. We virally expressed inhibitory hM4Di-DREADDs (designer receptors exclusively activated by designer drugs) in the deep cerebellar nuclei (Dentate, Interpositus and Fastigial nuclei), and examined the effects of this inhibitory action during motor skill learning using the accelerating rotarod test after clozapine-N-oxide (CNO) injection. By using a learning protocol (7 trials per day during 7 days) we observed distinct early (acquisition, Day 1) and late (consolidation, Days 2-7) phases in motor learning task. Importantly, our results showed that inhibition of deep cerebellar neurons produced an impairment in the beginning of the consolidation phase (Days 2-5) and then a retrieval effect was observed, suggesting that adaptive mechanisms could compensate for the lack of neuronal activity in deep cerebellar nuclei. The motor learning performance was not affected by CNO treatment in control mice. Open-field, horizontal bar, vertical pole and footprint tests were applied to evaluate locomotor activity and motor coordination. No significant differences were observed between the experimental conditions in any of these behavioral tests. In conclusion, our results indicate that deep cerebellar nuclei participate in the consolidation of motor skill learning.