Cerebellar interneuron activity is triggered by reach endpoint during learning of a complex locomotor task

Abstract

Locomotion in complex environments depends on the precise timing and active control of single paw movements in order to adapt steps to surface structure and coordinate paws. Such motor control crucially depends on the cerebellum. In turn, cerebellar activity is reported to reflect limb movement kinematics, but how precise action timing in complex environments is controlled by the cerebellar circuit is currently unknown. To address this question, we developed LocoReach: a new task which combines continuous and discrete aspects of motor control by requiring mice to walk on a runged treadmill, where each step involves reaching for the next rung. Over several days of learning, mice became increasingly proficient at LocoReach, so that they made fewer, longer strides with faster swings and fewer missteps. We assessed the cerebellar role during LocoReach learning through pharmacological inhibition as well as real-time optogenetic inhibition of cerebellar activity and electrophysiological recordings of molecular layer interneurons (MLIs), as they are thought to control the timing and gain of the cerebellar cortical output. Inhibiting cerebellar output during the swing phase of a specific paw led to shorter swings of this paw. When analyzing behaviorally-evoked responses in MLIs, we found sharp changes in activity around paw-specific transitions from swing to stance and vice versa. While most MLIs in the left simplex were preferentially modulated by the reach endpoint of the front left paw, a large proportion of cells additionally showed activity variations related to other paws or even multiple paws. Stronger firing rate modulations reflected longer strides made over learning, consistent with previous reports highlighting the role of the intermediate cerebellum in controlling reach endpoint precision. Our results provide the first demonstration that cerebellar inhibitory signals are tuned to specific events in the step cycle which can act as a powerful mechanism for the precise control of paw placements.

Publication
biorXiv
Date
Links
PDF