Activation of presynaptic GABAA receptors induces glutamate release from parallel fiber synapses

Abstract

The parallel fibers relay information coming into the cerebellar cortex from the mossy fibers, and they form synapses with molecular layer interneurons (MLIs) and Purkinje cells. Here we show that activation of ionotropic GABA receptors (GABAARs) induces glutamate release from parallel fibers onto both MLIs and Purkinje cells. These GABA-induced EPSCs have kinetics and amplitudes identical to random spontaneous currents (sEPSCs), but, unlike sEPSCs, they occur in bursts of between one and five successive events. The variation in amplitude of events within bursts is significantly less than the variation of all sEPSC amplitudes, suggesting that the bursts result from repetitive activation of single presynaptic fibers. Electron microscopy of immunogold-labeled α-1 subunits revealed GABAARs on parallel fiber terminals. We suggest that the activation of these receptors underlies the increased amplitude of parallel fiber-evoked Purkinje cell EPSCs seen with application of exogenous GABA or after the release of GABA from local interneurons. These results occur only when molecular layer GABAARs are activated, and the effects are abolished when the receptors are blocked by the GABAAR antagonist gabazine (5 μM). From these data, we conclude that GABAARs located on parallel fibers depolarize parallel fiber terminals beyond the threshold for Na+ channel activation and thereby induce glutamate release onto MLIs and Purkinje cells. Copyright © 2007 Society for Neuroscience.