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Authors & Affiliations
Alice Geminiani, Ana Gonçalves, Hugo Gravato Marques, Francesco Costantino, Tatiana Silva, Merit Kruse, Megan R. Carey
Abstract
The cerebellum plays a key role in motor learning, adapting movements in response to perturbations or errors. For simple tasks like eyeblink classical conditioning, climbing fibers originating in the inferior olive and projecting to the cerebellum provide neural instructive signals sufficient to drive learning. For complex whole-body behaviors like locomotion, however, it is not known what role climbing fibers play. We recently demonstrated (Darmohray et al., 2019) that mice running on a split-belt treadmill (that controls the speed under each side of the body independently) exhibit a form of learning called locomotor adaptation that has been extensively characterized in humans. In mice, as in humans, split-belt adaptation is cerebellum-dependent and reflects learned changes in interlimb symmetry.Here, we used optogenetics combined with real-time tracking of limb kinematics to test the hypothesis that climbing fiber activation can induce learned changes in gait symmetry. We find that unilateral optogenetic climbing fiber inhibition or activation, precisely locked to specific phases of the locomotor cycle, is sufficient to drive bidirectional, learned changes in interlimb symmetry, depending on the phase of the locomotor cycle when it occurs. These results reveal powerful climbing fiber control of interlimb coordination and its adaptation to external perturbations and open the door to potential neurotherapeutics for gait asymmetries.