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 s ite on NMDA-Rs is saturated. If this site were not saturated then glycine r eleased from glycinergic synaptic terminals might 'spill-over' and activate NMDA-Rs. Since motoneurons have both NMDA and glycine synapses these neuro ns present an optimal substrate for testing whether the glycine binding sit e of NMDA-Rs is activated by transmitter released from glycine synaptic ter minals. Using an in vitro brainstem slice preparation we report on initial experiments to investigate whether the glycine binding site of NMDA-Rs is s aturated in motoneurons. Specifically, we investigated the question of whet her the response of neonatal rat hypoglossal motoneurons (HMs) to a brief a pplication of NMDA is enhanced by the presence of exogenous glycine. We fou nd that exogenously applied glycine (1 mM) enhanced the NMDA activated memb rane current. We conclude that in brainstem slices the glycine site at moto neuronal NMDA-Rs is not saturated, and that synaptically-released glycine m ay modulate NMDA-Rs mediated responses. (C) Elsevier, Paris.