NR2B-containing receptors mediate cross talk among hippocampal synapses

Under some conditions, synaptically released glutamate can exert long-range actions in the cortical microcircuitry. To what extent glutamate spillover leads to direct cross talk among individual synapses remains unclear. We recorded NMDAR-mediated EPSCs in acute hippocampal slices at 35degreesC by stimulating two independent pathways that converge on the same CA1 pyramidal cell. Activation of a conditioning pathway in the presence of the use-dependent blocker dizocilpine maleate (MK801) resulted in partial NMDA receptor ( NMDAR) blockade in the other, silent pathway. This was accompanied by an increase in the rise time of the EPSCs in the conditioning ( although not the silent) pathway, implying an increase in diffusional distance from release site to NMDARs. We estimated that up to similar to 30% of NMDARs contributing to EPSCs were activated by glutamate released from multiple synaptic sources; however, NMDAR-mediated synaptic cross talk was undetectable when NR2B subunit-containing receptors were blocked ( but could be rescued by blocking glutamate uptake). We propose that NR2B-containing NMDARs can detect glutamate arising from multiple synapses, whereas NR2A-containing NMDARs only normally mediate direct synaptic transmission. These NMDAR isoforms thus play complementary roles in sensing global and local glutamate signals, respectively.