Migration of neocortical neurons in the absence of functional NMDA receptors.

A variety of factors, from cell adhesion to changes in intracellular calcium, are thought to influence neuronal migration. Here we examine the possibility that calcium influx mediated via NMDA receptors regulates migration of neocortical neurons. We have examined the cytoarchitecture of the cortex in transgenic mice lacking functional NMDA receptors. Using cell birthdating techniques we found that cells in the developing neocortex of NMDAR-1 mutant mice have a distribution indistinguishable from that in animals with functional NMDA receptors, implying normal rates and routes of migration. These observations contrast with previous in vitro pharmacological studies of cerebellar granule cell migration, in which a role for NMDA receptors has been demonstrated. Thus, either different mechanisms are responsible for controlling neuronal migration in neocortex versus cerebellum or, more likely, neocortical neurons in NMDAR-1 mutant mice have acquired compensatory mechanisms for cell migration.