MIGRATION OF NEOCORTICAL NEURONS IN THE ABSENCE OF FUNCTIONAL NMDA RECEPTORS

A variety of factors, from cell adhesion to changes in intracellular c alcium, are thought to influence neuronal migration. Here we examine t he possibility that calcium influx mediated via NMDA receptors regulat es migration of neocortical neurons. We have examined the cytoarchitec ture of the cortex in transgenic mice lacking functional NMDA receptor s. Using cell birthdating techniques we found that cells in the develo ping neocortex of NMDAR-1 mutant mice have a distribution indistinguis hable from that in animals with functional NMDA receptors, implying no rmal rates and routes of migration. These observations contrast with p revious in vitro pharmacological studies of cerebellar granule cell mi gration, in which a role for NMDA receptors has been demonstrated. Thu s, either different mechanisms are responsible for controlling neurona l migration in neocortex versus cerebellum or, more likely, neocortica l neurons in NMDAR-1 mutant mice have acquired compensatory mechanisms for cell migration.