Occurrence of long-term depression in the cerebellar flocculus during adaptation of optokinetic response

Takuma Inoshita,Tomoo Hirano

doi:10.7554/elife.36209

Abstract

Long-term depression (LTD) at parallel fiber (PF) to Purkinje cell (PC) synapses has been considered as a main cellular mechanism for motor learning. However, the necessity of LTD for motor learning was challenged by demonstration of normal motor learning in the LTD-defective animals. Here, we addressed possible involvement of LTD in motor learning by examining whether LTD occurs during motor learning in the wild-type mice. As a model of motor learning, adaptation of optokinetic response (OKR) was used. OKR is a type of reflex eye movement to suppress blur of visual image during animal motion. OKR shows adaptive change during continuous optokinetic stimulation, which is regulated by the cerebellar flocculus. After OKR adaptation, amplitudes of quantal excitatory postsynaptic currents at PF-PC synapses were decreased, and induction of LTD was suppressed in the flocculus. These results suggest that LTD occurs at PF-PC synapses during OKR adaptation.

Highlights

If Long-term depression (LTD) occurs during optokinetic response (OKR) training, the synaptic transmission at parallel fiber (PF)-Purkinje cell (PC) synapses should be depressed
The present results suggest that LTD occurs during OKR adaptation and support the involvement of LTD in motor learning
Previous study reported that OKR training reduced the number of AMPAtype glutamate receptors at PF-PC synapses in the H zone (Wang et al, 2014)

Summary

Introduction

LTD induction by different conditioning stimulation in the above transgenic mice was reported (Yamaguchi et al, 2016), and the ideas that multiple types of synaptic plasticity in the cerebellum contribute to motor learning, and that some types of plasticity might compensate defects of the other have been proposed (Boyden et al., 2004; Dean et al, 2010; Gao et al, 2012; Hirano, 2013). We used adaptation of optokinetic response (OKR) as a model of cerebellum-dependent motor learning and examined how it influenced LTD. Previous studies reported that the horizontal (H) zone of flocculus, a small region of cerebellum, is necessary for adaptation of horizontal OKR (Robinson, 1981; Nagao, 1988; du Lac et al, 1995; Boyden et al, 2004).

Results

Discussion

Materials and methods