PT - JOURNAL ARTICLE AU - Varani, Andres P AU - Mailhes-Hamon, Caroline AU - Sala, Romain W AU - Fouda, Sarah AU - Frontera, Jimena L AU - Léna, Clément AU - Popa, Daniela TI - Multiple Functions of Cerebello-Thalamic Neurons in Learning and Offline Consolidation of a Motor Skill in mice AID - 10.1101/2024.09.11.612475 DP - 2024 Jan 01 TA - bioRxiv PG - 2024.09.11.612475 4099 - http://biorxiv.org/content/early/2024/09/11/2024.09.11.612475.short 4100 - http://biorxiv.org/content/early/2024/09/11/2024.09.11.612475.full AB - Motor skill learning is a complex and gradual process that involves the cortex and basal ganglia, both crucial for the acquisition and long-term retention of skills. The cerebellum, which rapidly learns to adjust the movement, connects to the motor cortex and the striatum via the ventral and intralaminar thalamus respectively. Here, we evaluated the contribution of cerebellar neurons projecting to these thalamic nuclei in a skilled locomotion task in mice. Using a targeted chemogenetic inhibition that preserves the motor abilities, we found that cerebellar nuclei neurons projecting to the intralaminar thalamus contribute to learning and expression, while cerebellar nuclei neurons projecting to the ventral thalamus contribute to offline consolidation. Asymptotic performance, however, required each type of neurons. Thus, our results show that cerebellar neurons belonging to two parallel cerebello-thalamic pathways play distinct, but complementary, roles functioning on different timescales and both necessary for motor skill learning.Competing Interest StatementThe authors have declared no competing interest.