TEMPORAL CORRELATIONS BETWEEN FUNCTIONAL AND MOLECULAR-CHANGES IN NMDA RECEPTORS AND GABA NEUROTRANSMISSION IN THE SUPERIOR COLLICULUS

Activation of the NMDA subtype of glutamate receptor is required for a ctivity-dependent structural plasticity in many areas of the young bra in. Previous work has shown that NMDA receptor currents decline approx imately at the time that developmental synaptic plasticity ends, and i n situ hybridization studies have suggested that receptor subunit chan ges may be occurring during the same developmental interval. To establ ish a system in which the relationship between these properties of dev eloping synapses can be explored, we have combined patch-clamp recordi ngs with mRNA- and protein-level biochemical analyses to study the dev elopmental regulation of NMDA receptors in the superficial layers of t he rat superior colliculus. These experiments document an abrupt decre ase in the MDA receptor contribution to synaptic currents that occur b efore eye opening and is closely associated with changes in NR1 protei n, rapidly rising levels of the NMDA receptor subunit NR2A, and decrea sing levels of NR2B. The functional and molecular changes also are cor related with the developmental decline in structural plasticity in the se layers. In addition, both physiological and biochemical methods sho w evidence of GABA-mediated inhibition in the superficial collicular l ayers beginning after eye opening, This may provide an additional hete rosynaptic mechanism for controlling excitation and plasticity in this neuropil by pattern vision. thus our findings lend support to the ide a that high levels of NMDA receptor function are associated with the p otential for structural rearrangement in CNS neuropil and that the fun ctional downregulation of this molecule results, at least partially, f rom changes in its subunit composition.