PLASTICITY OF NMDA RECEPTOR EXPRESSION DURING MOUSE CEREBELLAR GRANULE CELL-DEVELOPMENT

A period of hypersensitivity to N-methyl-D-aspartate (NMDA) has been d escribed during the early development of different types of neuron. Si nce activation of NMDA receptors can also induce rapid neuron death, t he hypersensitivity to NMDA may be tightly controlled. In the present study we show that mouse cerebellar granule neurons become transiently hypersensitive to NMDA between days 10 and 14 after plating in a cult ure medium containing 30 mM K+. The NMDA sensitivity is higher when ce lls are cultured in the presence of an NMDA receptor antagonist [30 mM K+ plus 100 mu M +/-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic a cid (CPP)], and no hypersensitivity is observed when cells are culture d in the continuous presence of NMDA (12.5 mM K+ plus 100 mu M NMDA). The high NMDA sensitivity in control cells is associated with a higher density of NMDA receptors than that measured in NMDA-treated cells, s uggesting that the sensitivity to NMDA may be partly controlled by act ivity-dependent NMDA receptor down-regulation. We also examined the le vel of NMDA-zeta 1 mRNA and found no correlation between this paramete r and the transient pattern of NMDA sensitivity. Such NMDA receptor pl asticity may be of importance in the central nervous system, protectin g developing cells from excitotoxicity at critical developmental stage s.