Segregation of NMDA and non-NMDA receptors at separate synaptic contacts: evidence from spontaneous EPSPs in Xenopus embryo spinal neurons

Many excitatory amino acid (EAA)-mediated synaptic potentials are dual-component as a result of the simultaneous activation of N-methyl-d-asparate (NMDA) and non-NMDA receptor subtypes, the two major classes of EAA receptor in vertebrates. This raises the question of whether the two receptor types are located separately or together at individual synaptic contacts. Support for the segregation of NMDA and non-NMDA receptors in discrete anatomical patches arises from the observation that the fast and slow components of dual-component potentials mediated via NMDA and non-NMDA receptor types can fail independently. We have obtained further support for this by investigating the spontaneous release of EAA neurotransmitter at sensory synapses in the spinal cord of Xenopus leavis embryos. We report the occurence of spontaneous TTX-resistant EPSPs in sensory interneurons that are mediated by EAA receptors. These spontaneous potentials share the same pharmacological sensitivities as EPSPs evoked by skin sensory afferents, being blocked by kynurenic acid and reduced by (±)-2-amino-5-phosphonovaleric acid (APV). The spontaneousEPSPs differ from evoked EPSPs in their time courses: while evoked EPSPs are almost exclusively of the dual-component variety, the spontaneous EPSPs are predominantly either fast or slow. These data suggest that spontaneous EPSPs reflect release of EAA neurotransmitter at synaptic contacts overlying homogeneous populations of either NMDA or non-NMDA receptors. Their relatively large size, up to 50% or more of the amplitude of unitary EPSPs evoked by stimulation, also suggests that synapses between skin afferents and sensory interneurons may comprise relatively few points of synaptic contact. Since the majority of spontaneous EPSPs are of the fast variety we suggest that most synaptic contacts overlie patches of non-NMDA receptors.