Low resting potential and postnatal upregulation of NMDA receptors may cause Cajal-Retzius cell death

Using in situ patch-clamp techniques in rat telencephalic slices, we have f ollowed resting potential (RP) properties and the functional expression of NMDA receptors in neocortical Cajal-Retzius (CR) cells from embryonic day 1 8 to postnatal day 13, the time around which these cells normally disappear We find that throughout their lives CR cells have a relatively depolarized RP (approximately -50 mV), which can be made more hyperpolarized (approxim ately -70 mV) by stimulation of the Na/K pump with intracellular ATP, The N MDA receptors of CR cells are subjected to intense postnatal upregulation, but their similar properties (EC50, Hill number, sensitivity to antagonists , conductance, and kinetics) throughout development suggest that their subu nit composition remains relatively homogeneous. The low RP of CR cells is w ithin a range that allows for the relief of NMDA channels from Mg2+ blockad e. Our findings are consistent with the hypothesis that CR cells may degene rate and die subsequent to uncontrolled overload of intracellular Ca2+ via NMDA receptor activation by ambient glutamate. In support of this hypothesi s we have obtained evidence showing the protection of CR cells via in vivo blockade of NMDA receptors with dizocilpine.