Stimulation of the N-methyl-d-aspartate receptor has a trophic effect on differentiating cerebellar granule cells

Abstract N- methyl- d -aspartate (NMDA) supplementation of cerebellar cultures enriched in granule neurones (about 90%) prevented the extensive cell loss which occurs when cultivation takes place, in serum containing media, in the presence of ‘low’ K + (5–15 mM). Estimation of tetanus toxin receptors and N-CAM contents indicated that NMDA rescued primarily nerve cells. The influence of NMDA in promoting cell survival was blocked by the receptor antagonist, 2-amino-5-phosphonovalerate. The effect depended both on the concentration of NMDA and on the degree of depolarization of cells, the affinity in the presence of 15 mM K + being similar to that of NMDA receptor binding. The results attest a new role for excitatory amino acid transmitters by showing that they can exert a stage-dependent trophic action on developing nerve cells.