Long-term survival, migration, and differentiation of neural cells withoutfunctional NMDA receptors in vivo

The NMDA receptor, one of the two major ionotropic glutamate receptors, has been proposed to play fundamental roles in the survival, migration, differ entiation, 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 post natal neurons. The properties of cells lacking the NR1 subunit of NMDA rece ptors 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 trans plantation (Brustle et at, 1995, Neuron 15, 1275-1285). The transplanted ce lls took part in the normal development of the host brain where they surviv ed after migration into a large number of brain structures. Morphological a nd immunohistochemical analysis suggests that NR1 -/- cells can differentia te normally in these sites. The results provide evidence that NMDA-receptor -initiated signals are not required for the postnatal differentiation and s urvival of many types of neurons in the central nervous system, in a noncel l autonomous fashion after transplantation into a wild-type environment. (C ) 2001 Academic Press.