Dual contributions of cerebellar-thalamic networks to the consolidation and maintenance of a motor learning task.

VARANI ANDRÉS P.; FRONTERA JIMENA L.; MAILHES-HAMON CAROLINE ; POPA DANIELA; SALA ROMAIN; LENA CLEMENT

Congreso; 12th Virtual Forum FENS; 2020

Motor learning has been shown to involve several brain structures, including the cerebellum, the basal ganglia and the motor cortex. The cerebellum is connected to the two other structures by way of distinct pathways. Here, we evaluated the contribution of the cerebello-thalamic pathways targeting the basal ganglia and motor cortex to the acquisition, consolidation and maintenance of a skilled locomotor task in mice. We first found that neurons from the Dentate and Interposed nuclei of the cerebellum were mostly down-modulated by speed along the protocol, in opposition to thalamic neurons who displayed both positive and negative modulations. In the case of the Dentate-Intralaminar thalamus pathway, those modulations seemed to converge during consolidation and maintenance phase, whereas the proportion of similar modulations in the Interposed-Motor thalamus pathway remained stable along the different phases of learning, suggesting an early engagement of this pathway. We then examined the impact on learning of a specific and transient inhibition of cerebellar nuclei neurons using hM4Di-DREADDs. The inhibition of cerebellar nuclei neurons produced impairment in the beginning of the consolidation phase and during the maintenance phase, suggesting that cerebellum has a dual contribution to learning. We then targeted specific cerebello-thalamic pathways by combining injections of viruses in the thalamus and in the cerebellar nuclei. The results confirmed that the pathways targeting the Dentate-intralaminar and Interposed-motor thalamus contributed respectively to the maintenance and consolidation phases of learning. In conclusion, our results suggest that two parallel cerebellar-thalamic pathways perform distinct computations operating on distinct timescales in motor learning.