Climbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling

Climbing fibers (CFs) from the inferior olive (IO) make strong excitatory synapses onto cerebellar Purkinje cell (PC) dendrites, and trigger distinctive responses known as complex spikes (CSs). We find that in awake mice, a CS in one PC suppresses conventional simple spikes (SSs) in neighboring PCs for several milliseconds. This involves a novel ephaptic coupling, in which an excitatory synapse generates large negative extracellular signals that nonsynaptically inhibit neighboring PCs. The distance dependence of CS-SS ephaptic signaling, combined with the known CF divergence, 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, either as a result of ephaptic signaling or other mechanisms, can effectively promote firing in neurons in the deep cerebellar nuclei with remarkable speed and precision.