J. Shi et al., TEMPORAL CORRELATIONS BETWEEN FUNCTIONAL AND MOLECULAR-CHANGES IN NMDA RECEPTORS AND GABA NEUROTRANSMISSION IN THE SUPERIOR COLLICULUS, The Journal of neuroscience, 17(16), 1997, pp. 6264-6276
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.