Climbing fiber synapses rapidly inhibit neighboring Purkinje cells via ephaptic coupling

Climbing fibers (CFs) from the inferior olive (IO) provide strong excitatory inputs onto the dendrites of cerebellar Purkinje cells (PC), and trigger distinctive responses known as complex spikes (CSs). We find that in awake, behaving mice, a CS in one PC suppresses conventional simple spikes (SSs) in neighboring PCs for several milliseconds. This involves a novel form of ephaptic coupling, in which an excitatory synapse nonsynaptically inhibits neighboring cells by generating large negative extracellular signals near their dendrites. The distance dependence of CS-SS ephaptic signaling, combined with the known divergence of CF synapses made by IO neurons, allows a single IO neuron to influence the output of the cerebellum by synchronously suppressing the firing of potentially over one hundred PCs. Optogenetic studies in vivo and dynamic clamp studies in slice indicate that such brief PC suppression can effectively promote firing in neurons in the deep cerebellar nuclei and motor thalamus.