Slow glycinergic transmission mediated by transmitter pooling

Abstract

Most fast-acting neurotransmitters are rapidly cleared from synaptic regions. This feature isolates synaptic sites, rendering the timecourse of synaptic responses independent of the number of active synapses. We describe a striking exception at glycinergic synapses on granule cells of the rat dorsal cochlear nucleus. The duration of IPSCs was dependent on the number of presynaptic axons that were stimulated and on the number of vesicles released from each axon. Increasing stimulus number or frequency, or blocking glycine uptake, slowed synaptic decays, while a low-affinity competitive antagonist of GlyRs accelerated IPSC decay. These effects could be explained by unique features of GlyRs when activated by pooling of glycine across synapses. Functionally, increasing the number of IPSPs markedly lengthened the period of spike inhibition following cessation of presynaptic stimulation. Thus, temporal properties of inhibition can be controlled by activity levels in multiple presynaptic cells or by adjusting release probability at individual synapses.