Cell-specific functional connectivity of cerebellar outputs for locomotor learning

Everyday behaviours, like mastering dance moves or hiking through uneven terrains, require motor learning.

Although essential, cellular and circuit mechanisms for this type of learning are poorly understood.In the context of locomotion, learning can be induced on a split-belt treadmill, where each side of the body moves at different speeds; this is currently used as a rehabilitative therapy in patients presenting asymmetric gaits following brain damage.

The receiving laboratory recently showed that mouse locomotor learning is remarkably similar to humans. Regaining gait symmetry is achieved through specific adjustments in interlimb coordination. Moreover, the laboratory demonstrated that this form of motor learning depends critically on intermediate cerebellum.

Strikingly, spatial and temporal components of learning (i.e. “where” and “when” paws land) proceeded independently, suggesting that they might be dissociable at the neural circuit level.

However, how cerebellar outputs act to calibrate spatiotemporal coordination between limbs is unknown.IP2adapt aims to decipher the functional connectivity of cerebellar output circuits conveying corrective calibration signals to modify locomotor movements in space and time.

Specifically, we will: 1) Use advanced viral tools to map output circuits downstream of the cerebellum and identify candidates for spatial and temporal calibration signals; 2) Use high-resolution quantitative behavioural analysis and cutting-edge circuit manipulation to test specific functional roles of projection-defined subsets of cerebellar outputs in locomotor learning; 3) Use state-of-the-art recordings of these functionally-defined neurons during learning to understand how the cerebellum transforms locomotor errors into spatial and temporal calibration of limb movement.

This work will reveal unprecedented insights into neural circuits that ensure the adaptability of motor commands, with direct relevance for rehabilitative therapy.