D-SERINE AS A NEUROMODULATOR - REGIONAL AND DEVELOPMENTAL LOCALIZATIONS IN RAT-BRAIN GLIA RESEMBLE NMDA RECEPTORS

D-Serine is localized in mammalian brain to a discrete population of g lial cells near NMDA receptors, suggesting that D-serine is an endogen ous agonist of the receptor-associated glycine site. To explore this p ossibility, we have compared the immunohistochemical localizations of D-serine, glycine, and NMDA receptors in rat brain, In the telencephal on, D-serine is concentrated in protoplasmic astrocytes, which are abu ndant in neuropil in close vicinity to NMDA receptor 2A/B subunits. Ul trastructural examination of the CA1 region of hippocampus reveals D-s erine in the cytosolic matrix of astrocytes that ensheath neurons and blood vessels, whereas NR2A/B is concentrated in dendritic spines. By contrast, glycine immunoreactivity in telencephalon is the lowest in b rain. During postnatal week 2, D-serine levels in cerebellum are compa rable to those in adult cerebral cortex but fall to undetectable level s by day 26. During week 2, we observe parallel ontogeny of D-serine i n Bergmann glia and NR2A/B in Purkinje cells, suggesting a role for as trocytic D-serine in NMDA receptor-mediated synaptogenesis. D-Serine i n the radial processes of Bergmann glia is also well positioned to reg ulate NMDA receptor-dependent granule cell migration, In the inner gra nule layer, D-serine is found transiently in protoplasmic astrocytes s urrounding glomeruli, where it could regulate development of the messy fiber/granule cell synapse. D-Serine seems to be the endogenous ligan d of glycine sites in the telencephalon and developing cerebellum, whe reas glycine predominates in the adult cerebellum, olfactory bulb, and hindbrain.