JournalNeural Excitability, Synapses, and Glia

Graded Control of Climbing-Fiber-Mediated Plasticity and Learning by Inhibition in the Cerebellum

Control of synaptic plasticity by molecular layer interneurons. (A) Pairing protocol used to generate associative plasticity in floccular slices. Below are averaged test postsynaptic potentials evoked by parallel fiber stimulation from the same cell before and after the pairing protocol. (B) Conjunctive Climbing fibers stimulation occurring coincident with a moderate level of Channelrhodopsin-induced molecular layer interneurons activation. Below are averaged test postsynaptic potentials evoked by parallel fiber stimulation from the same cell before and after the pairing protocol. (C) Climbing fibers were stimulated coincident with intensive activation of molecular layer interneurons during the pairing procedure. Below are averaged test postsynaptic potentials evoked by parallel fiber stimulation from the same cell before and after the pairing protocol. (D) During the stimulus protocol, molecular layer interneurons were activated following the parallel fiber tetanus.

Purkinje cell dendrites convert excitatory climbing fiber input into signals that instruct plasticity and motor learning. Modulation of instructive signaling may increase the range in which learning is encoded, yet the mechanisms that allow for this are poorly understood. We found that optogenetic activation of molecular layer interneurons (MLIs) that inhibit Purkinje cells suppressed climbing-fiber-evoked dendritic Ca2+ spiking. Inhibitory suppression of Ca2+ spiking depended on the level of MLI activation and influenced the induction of associative synaptic plasticity, converting climbing-fiber-mediated potentiation of parallel fiber-evoked responses into depression. In awake mice, optogenetic activation of floccular climbing fibers in association with head rotation produced an adaptive increase in the vestibulo-ocular reflex (VOR). However, when climbing fibers were co-activated with MLIs, adaptation occurred in the opposite direction, decreasing the VOR. Thus, MLIs can direct a continuous spectrum of plasticity and learning through their influence on Purkinje cell dendritic Ca2+ signaling.


Matthew J.M. Rowan, Audrey Bonnan, Ke Zhang, Samantha B. Amat, Chikako Kikuchi, Hiroki Taniguchi, George J. Augustine, and Jason M. Christie. Neuron 2018, Online Publication.
https://www.cell.com/neuron/abstract/S0896-6273(18)30598-1

Share