A DISINHIBITORY MICROCIRCUIT FOR GATED CEREBELLAR LEARNING

Performance motor errors trigger animals’ adaptive learning behaviors to improve the accuracy and efficiency of the movement. The cerebellum is one of the key brain centers for encoding motor performance and motor learning. Climbing fibers relay information related to motor errors to the cerebellar cortex, evoking elevation of intracellular Ca2+ signals at Purkinje cell dendrites and inducing plasticity at coactive parallel fiber synapses, ultimately recalibrating sensorimotor associations to alter behavior. Molecular layer interneurons (MLIs) inhibit Purkinje cells to modulate dendritic excitability and action potential output. How MLIs contribute to the regulation and encoding of climbing fiber-evoked adaptive movements remains poorly understood. In this dissertation, I used genetic tools to manipulate the activity of MLIs while monitoring Purkinje cell dendritic activity during a cerebellum-dependent motor learning task with different contexts to evaluate how MLIs are involved in this process. The results show that by suppressing dendritic Ca2+ signals in Purkinje cells, MLI activity coincident with climbing fiber-mediated excitation prevents the occurrence of learning when adaptation is not necessary. On the other hand, with error signals present, disinhibition onto Purkinje cells, mediated by MLI-MLI microcircuit, unlocked the ability of climbing fibers to induce plasticity and motor learning.