NMDA receptor regulation of neuronal morphology in cultured hippocampal neurons

The relationship of the activity of specific neurotransmitter receptors to neuronal morphology was studied in cultured dentate granule neurons from embryonic rat hippocampus. These experiments were made possible by the development of a defined serum-free culture medium for growth at densities low enough to observe isolated neurons. N-Methyl-D-aspartate (NMDA) and its specific non-competitive antagonist, MK801, affected neuronal morphology in a reciprocal fashion. Like glutamate, NMDA stimulated extensive branching of neuronal processes. Not only was 75% of the branching blocked by MK801, but the longest process was 250% longer in the presence of MK801. These results suggest that neurotransmitters that act on the NMDA receptor may contribute to development and synaptogenesis.