Evidence for functional co-activation of N-methyl-D-aspartate receptors by glycine

The excitatory neurotransmitter glutamate acts at several receptor subtypes in the CNS, including N-methyl-D-aspartate (NMDA) receptors. The inhibitory neurotransmitter glycine is a co-agonist of NMDA receptors and functional glycinergic co-activation of NMDA receptors is theoretically possible due to the presence of background glutamate. We report the first high fidelity recording of a distinct NMDA receptor excitatory post-synaptic potential (EPSP) in the intact mammalian CNS. The EPSP was evoked by multi-shock activation of a glycinergic pathway rather than a glutamatergic pathway and had characteristics most compatible with glycine, rather than glutamate, activation of NMDA receptors.