NMDA receptor content of synapses in stratum radiatum of the hippocampal CA1 area

Glutamate receptors activated by NMDA (NMDARs) or AMPA (AMPARs) are cluster ed on dendritic spines of pyramidal cells. Both the AMPAR-mediated postsyna ptic responses and the synaptic AMPAR immunoreactivity show a large intersy napse variability. Postsynaptic responses mediated by NMDARs show less vari ability. To assess the variability in NMDAR content and the extent of their coexistence with AMPARs in Schaffer collateral-commissural synapses of adu lt rat CA1 pyramidal cells, electron microscopic immunogold localization of receptors has been used. Immunoreactivity of NMDARs was detected in virtua lly all synapses on spines, but AMPARs were undetectable, on average, in 12 % of synapses. A proportion of synapses had a very high AMPAR content relat ive to the mean content, resulting in a distribution more skewed toward lar ger values than that of NMDARs. The variability of synaptic NMDAR content [ coefficient of variation (CV), 0.64-0.70] was much lower than that of the A MPAR content (CV, 1.17-1.45). Unlike the AMPAR content, the NMDAR content s howed only a weak correlation with synapse size. As reported previously for AMPARs, the immunoreactivity of NMDARs was also associated with the spine apparatus within spines. The results demonstrate that the majority of the s ynapses made by CA3 pyramidal cells onto spines of CA1 pyramids express bot h NMDARs and AMPARs, but with variable ratios. A less-variable NMDAR conten t is accompanied by a wide variability of AMPAR content, indicating that th e regulation of expression of the two receptors is not closely linked. Thes e findings support reports that fast excitatory transmission at some of the se synapses is mediated by activation mainly of NMDARs.