Modulation of motoneuron N-methyl-D-aspartate receptors by the inhibitory neurotransmitter glycine.

Previous studies in the central nervous system have shown that glycine is a co-agonist with glutamate at central N-methyl-D-aspartate receptors (NMDA-Rs). However, there is considerable controversy as to whether the glycine site on NMDA-Rs is saturated. If this site were not saturated then glycine released from glycinergic synaptic terminals might 'spill-over' and activate NMDA-Rs. Since motoneurons have both NMDA and glycine synapses these neurons present an optimal substrate for testing whether the glycine binding site of NMDA-Rs is activated by transmitter released from glycine synaptic terminals. Using an in vitro brainstem slice preparation we report on initial experiments to investigate whether the glycine binding site of NMDA-Rs is saturated in motoneurons. Specifically, we investigated the question of whether the response of neonatal rat hypoglossal motoneurons (HMs) to a brief application of NMDA is enhanced by the presence of exogenous glycine. We found that exogenously applied glycine (1 mM) enhanced the NMDA activated membrane current. We conclude that in brainstem slices the glycine site at motoneuronal NMDA-Rs is not saturated, and that synaptically-released glycine may modulate NMDA-Rs mediated responses.