Membrane potential dynamics of cerebellar nuclei neurons during eyeblink conditioning

Abstract

AbstractLearning to associate a cue with its aversive consequence enables animals to prevent harm. Associative conditioning relies on activity within the cerebellum, but little is known about how changes in synaptic inputs to its output neurons shape their membrane potential dynamics during learning. Here we studied these changes in inputs using whole-cell and juxtasomal recordings of cerebellar nucleus neurons in awake mice during eyeblink conditioning and doing post-learning structural analysis. We identified changes in mossy fiber- and Purkinje cell-, but not climbing fiber-, inputs, leading to changes in subthreshold processing that correlate with the level and direction of the conditioned eyelid movements. These changes appear sufficient, as optogenetic stimulation of the inputs evoke incremental eyelid closures over the course of conditioning. Our data reveal how electrophysiological and structural modifications at the level of synaptic inputs to cerebellar output neurons facilitate conditioning of eyelid movements.