Regulation and functional roles of rebound potentiation at cerebellar stellate cell—Purkinje cell synapses

Shin-Ya Kawaguchi,Tomoo Hirano

doi:10.3389/fncel.2014.00042

Abstract

Purkinje cells receive both excitatory and inhibitory synaptic inputs and send sole output from the cerebellar cortex. Long-term depression (LTD), a type of synaptic plasticity, at excitatory parallel fiber–Purkinje cell synapses has been studied extensively as a primary cellular mechanism of motor learning. On the other hand, at inhibitory synapses on a Purkinje cell, postsynaptic depolarization induces long-lasting potentiation of GABAergic synaptic transmission. This synaptic plasticity is called rebound potentiation (RP), and its molecular regulatory mechanisms have been studied. The increase in intracellular Ca2+ concentration caused by depolarization induces RP through enhancement of GABAA receptor (GABAAR) responsiveness. RP induction depends on binding of GABAAR with GABAAR associated protein (GABARAP) which is regulated by Ca2+/calmodulin-dependent kinase II (CaMKII). Whether RP is induced or not is determined by the balance between phosphorylation and de-phosphorylation activities regulated by intracellular Ca2+ and by metabotropic GABA and glutamate receptors. Recent studies have revealed that the subunit composition of CaMKII has significant impact on RP induction. A Purkinje cell expresses both α- and β-CaMKII, and the latter has much higher affinity for Ca2+/calmodulin than the former. It was shown that when the relative amount of α- to β-CaMKII is large, RP induction is suppressed. The functional significance of RP has also been studied using transgenic mice in which a peptide inhibiting association of GABARAP and GABAAR is expressed selectively in Purkinje cells. The transgenic mice show abrogation of RP and subnormal adaptation of vestibulo-ocular reflex (VOR), a type of motor learning. Thus, RP is involved in a certain type of motor learning.

Highlights

The cerebellum consists of cortex and nuclei, and is involved in motor control (Figure 1; Ito, 1984, 2011; Llinás et al, 2004)
At GABAergic synapses formed by stellate cells on Purkinje cells, three types of plasticity induced by postsynaptic depolarization have been reported (Figure 2), namely, depolarizationinduced suppression of inhibition (DSI), depolarization-induced
DSI is short-lasting suppression of presynaptic GABA release mediated by endocannabinoid, which is released from a Purkinje cell and binds to presynaptic cannabinoid receptor (Llano et al, 1991; Yoshida et al, 2002)

Summary

CELLULAR NEUROSCIENCE

Reviewed by: Enrico Cherubini, International School for Advanced Studies, Italy Laurens Bosman, Erasmus MC, Netherlands Purkinje cells receive both excitatory and inhibitory synaptic inputs and send sole output from the cerebellar cortex. Long-term depression (LTD), a type of synaptic plasticity, at excitatory parallel fiber–Purkinje cell synapses has been studied extensively as a primary cellular mechanism of motor learning. At inhibitory synapses on a Purkinje cell, postsynaptic depolarization induces long-lasting potentiation of GABAergic synaptic transmission. This synaptic plasticity is called rebound potentiation (RP), and its molecular regulatory mechanisms have been studied. The functional significance of RP has been studied using transgenic mice in which a peptide inhibiting association of GABARAP and GABAAR is expressed selectively in Purkinje cells.

INTRODUCTION

Cerebellar inhibitory synaptic plasticity

CONCLUSION