Open AccessClimbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling
Author(s) -
Kwan Hee Han,
Christopher H. Chen,
Mehak Khan,
Chong Guo,
Wade G. Regehr
Publication year - 2020
Publication title -
nature neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 13.403
H-Index - 422
eISSN - 1546-1726
pISSN - 1097-6256
DOI - 10.1038/s41593-020-0701-z
Subject(s) - climbing fiber , neuroscience , parallel fiber , excitatory postsynaptic potential , optogenetics , purkinje cell , cerebellum , deep cerebellar nuclei , synapse , coupling (piping) , extracellular , chemistry , cerebellar cortex , biophysics , biology , inhibitory postsynaptic potential , microbiology and biotechnology , materials science , metallurgy
Climbing fibers from the inferior olive make strong excitatory synapses onto cerebellar Purkinje cell (PC) dendrites and trigger distinctive responses known as complex spikes. We found that, in awake mice, a complex spike in one PC suppressed conventional simple spikes in neighboring PCs for several milliseconds. This involved a new ephaptic coupling, in which an excitatory synapse generated large negative extracellular signals that nonsynaptically inhibited neighboring PCs. The distance dependence of complex spike-simple spike ephaptic signaling, combined with the known CF divergence, allowed a single inferior olive neuron to influence the output of the cerebellum by synchronously suppressing the firing of potentially over 100 PCs. Optogenetic studies in vivo and dynamic clamp studies in slice indicated that such brief PC suppression, as a result of either ephaptic signaling or other mechanisms, could effectively promote firing in neurons in the deep cerebellar nuclei with remarkable speed and precision.