Cerebello-thalamo-cortical network modulates motor skill learning in mice

VARANI ANDRÉS P.; MAILHES-HAMON CAROLINE; YOUMIR RIHAM; PERRIN ELODIE; MENARDY FABIEN; LÉNA CLÉMENT; POPA DANIELA

Congreso; GDR Neuralet, 7th annual meeting.; 2016

Clinical and preclinical studies demonstrate that the cerebello-thalamo-cortical network is involved in motor skill learning. However, how cerebellar outputs could modulate this behavior remains unclear. On one hand, we evaluated the role of cerebello-thalamo-cortical network during motor skill learning (7 trials per day during 7 days) by using in vivo multi-channels recordings. At behavioral level, we were able to distinguish early (acquisition, Day 1) and late (consolidation, Days 2-7) phases in motor learning task. In addition, the electrophysiological recordings have shown decreased thalamic and thalamic-cortical activity during the early and late phases, respectively. On the other hand, 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 (designed receptors exclusively activated by drugs) in the deep cerebellar nuclei (Dentate, Interpositus and Fastigial nuclei), and we examined the effects of this inhibitory action during motor skill learning using the accelerating rotarod test after clozapine-N-oxide (CNO) injection. 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 the 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 cerebello-thalamo-cortical network participates in the consolidation of motor skill learning.