N-methyl-D-aspartate receptor blockade affects polysialylated neural cell adhesion molecule expression and synaptic density during striatal development

Glutamatergic neurons innervate the striatum and form asymmetric synapses w ith the dendritic spines of striatal efferent neurons. The role of glutamat e in striatal development, however, remains largely unknown. Previous studi es have shown a dramatic increase in the density of asymmetric synapses in the rat striatum during the third postnatal week, followed by a decrease to adult levels by postnatal day 25. At the same time, the highly polysialyla ted form of the neural cell adhesion molecule becomes progressively restric ted to synaptic regions and then disappears. We have now examined the effec ts of antagonists of the N-methyl-D-aspartate subtype of glutamatergic rece ptors on the expression of the polysialylated form of the neural cell adhes ion molecule and on synaptic density during this late period of striatal de velopment. Peripheral administration of the N-methyl-D-aspartate receptor a ntagonist dizocilpine maleate markedly decreased immunoreactivity for the h ighly polysialylated form of the neural cell adhesion molecule in the dorso lateral striatum and cerebral cortex when drug treatment included postnatal day 20, but not earlier in development. This effect was regionally specifi c and loss of the polysialylated neural cell adhesion molecule in the stria tum was reproduced by the local administration of dizocilpine maleate, DL-2 -amino-5-phosphonovalerate or ketamine on postnatal day 20. Quantitative ul trastructural studies of synaptic density with the physical disector method performed after one of the regimens inducing loss of the polysialylated ne ural cell adhesion molecule (postnatal days 18-20) revealed a 30% decrease in asymmetric synapses in the dorsolateral striatum of treated rats. Symmet ric synapses, which presumably do not use glutamate, were not affected. The data indicate that N-methyl-D-aspartate receptors play a role in the la te stages of synaptogenesis in the striatum and suggest that a subset of sy napses expressing immunoreactivity for the highly polysialylated form of th e neural cell adhesion molecule may be dependent on N-methyl-D-aspartate re ceptor stimulation during a critical period of striatal development. (C) 19 99 IBRO. Published by Elsevier Science Ltd.