Long-Term Survival, Migration, and Differentiation of Neural Cells without Functional NMDA Receptors in Vivo

Abstract

The NMDA receptor, one of the two major ionotropic glutamate receptors, has been proposed to play fundamental roles in the survival, migration, differentiation, and activity-dependent maturation of neural cells. The NR1 gene encodes the major subunit that is responsible for channel function, and NR1 −/− mice die at birth, inhibiting the study of glutamate signaling in postnatal neurons. The properties of cells lacking the NR1 subunit of NMDA receptors were studied by transplanting dissociated telencephalic, diencephalic, and mesencephalic cells of E14 mouse embryos with a targeted deletion of the NR1 gene into the ventricles of embryonic rats using intrauterine transplantation (Brüstle et al., 1995, Neuron 15, 1275–1285). The transplanted cells took part in the normal development of the host brain where they survived after migration into a large number of brain structures. Morphological and immunohistochemical analysis suggests that NR1 −/− cells can differentiate normally in these sites. The results provide evidence that NMDA-receptor-initiated signals are not required for the postnatal differentiation and survival of many types of neurons in the central nervous system, in a noncell autonomous fashion after transplantation into a wild-type environment.