Rapid alteration of synaptic number and postsynaptic thickening length by NMDA: an electron microscopic study in the...

The N-methyl-D-aspartate (NMDA) receptor has been widely implicated in numerous activity-dependent models of neural plasticity, learning, and memory. The formation of new synapses is a major assumption of the neural basis of learning. The current research was conducted to determine whether NMDA receptor activation could induce synaptic formation and, if so, whether this ability would mirror developmental changes in NMDA receptors. Rats at various developmental ages were given a single intraperitoneal injection of NMDA and sacrificed at various brief postinjection intervals (0.5-2 hr). The rats showed an age-dependent decline in the behavioral response to NMDA, as evidenced by reduced seizure activity and duration. Quantitative electron microscopic observations on the molecular layer of the occipital cortex, an area rich in NMDA receptors, revealed a transient increase in the length of postsynaptic thickenings in 17- and 35-day-old animals, appearing within 0.5 hr of injection. At 1 and 2 hr postinjection, an increase in synaptic density (number of synapses) was observed in 8-day-old animals. These results provide evidence that NMDA administration alone is capable of rapidly inducing alterations in synaptic structure and the formation of new synapses, underscoring the importance of the NMDA receptor in synaptogenesis and synaptic structural plasticity.