Dual contributions of cerebellar-thalamic networks to learning and offline consolidation of a complex motor task

Abstract

SUMMARYThe contribution of cerebellum to motor learning is often considered to be limited to adaptation, a short-timescale tuning of reflexes and previous learned skills. Yet, the cerebellum is reciprocally connected to two main players of motor learning, the motor cortex and the basal ganglia, via the ventral and midline thalamus respectively. Here, we evaluated the contribution of cerebellar neurons projecting to these thalamic nuclei in a skilled locomotion task in mice. In the cerebellar nuclei, we found task-specific neuronal activities during the task, and lasting changes after the task suggesting an offline processing of task-related information. Using pathway-specific inhibition, we found that dentate neurons projecting to the midline thalamus contribute to learning and retrieval, while interposed neurons projecting to the ventral thalamus contribute to the offline consolidation of savings. Our results thus show that two parallel cerebello-thalamic pathways perform distinct computations operating on distinct timescales in motor learning.

The cerebellum regulates fear extinction through thalamo-prefrontal cortex interactions in male mice

“…Specific chemogenetic inhibition of the FN neurons projecting to MD was carried out by bilateral injection of 250 nl of a retrograde virus expressing a cre-recombinase in the MD (CAV2-cre-GFP, from Platforme de Vectorologie de Montpellier) in combination with the infusion of 200 nl of inhibitory cre-dependent DREADD (AAV-hSyn-DIO-hM4Di-mCherry, Addgene) bilaterally in FN, adapted from previous works in our team 72 which demonstrated a strong reduction in cerebellar nuclei firing rate upon injection of CNO (1 mg/kg). The behavioral experiments started 10-14 days after the surgery, to ensure the expression of the receptors and the recovery of the mice.…”