Regulation of PSA-NCAM expression in the developing rat striatum

The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) plays a critical role in the maturation of the nervous system; however, little is known about its regulation. The timing of PSA-NCAM loss during development is region-specific and may indicate a loss of plasticity. In the striatum, PSA-NCAM loss occurs during the fourth postnatal week, after the formation of glutamatergic corticostriatal synapses and concurrently with a decrease in asymmetric synapses. Studies in Xenopus optic tectum and in glial cell cultures suggest that glutamatergic NMDA receptors play a role in the regulation of PSA-NCAM. We hypothesized that loss of PSA-NCAM expression during striatal development is regulated by corticostriatal inputs and NMDA receptor stimulation. Thermocoagulatory lesions of the sensorimotor cortex were performed on postnatal day 14, prior to corticostriatal synapse formation, and PSA-NCAM expression, synapse number and cortical projections were examined in the striatum. In addition, we examined the effects of peripherally and centrally administered NMDA antagonists on PSA-NCAM expression and synapse number in the striatum. Cortical lesions prolonged PSA-NCAM expression in the striatum and triggered the sprouting of crossed corticostriatal afferents from the spared homotypic cortex. In addition, synapse numbers were maintained in the denervated striatum. In contrast to cortical lesions, peripheral and local injections of NMDA antagonists induced a loss of PSA-NCAM and a decrease in asymmetrical synapses in the striatum. Although synapse loss accounts for some of its decrease, PSA-NCAM expression was also down regulated at synapses that were maintained after treatment. This effect was selective for PSA-NCAM, as expression of the adult form of NCAM was maintained. These data provide the first evidence that NMDA receptors play a critical role in the regulation of PSA-NCAM expression during development in mammals. In addition, the data suggest that PSA-NCAM expression in the striatum is regulated by corticostriatal afferents, and that these afferents retain a high level of plasticity as late as postnatal day 14. Finally, the data provide an experimental method for delaying PSA-NCAM loss in the striatum which will aid in defining the critical factors regulating PSA-NCAM expression during development