Long-term specification of AMPA receptor properties after synapse formation

AMPA receptors expressed at auditory nerve synapses in the mammalian and avian cochlear nuclei display exceptionally rapid channel gating, an adaptation well suited for acoustic processing. We examined whether cellular interactions during development might determine the subunit composition of these receptors. After synapse formation in the avian nucleus magnocellularis (nMag) in vivo, the rate of receptor desensitization increased threefold, sensitivity to channel block by polyamines increased, and sensitivity to cyclothiazide, an inhibitor of desensitization, increased, indicating a reduction in glutamate receptor subunit 2 and of flip splice variants. This phenotypic switch was prevented, but not reversed, by isolating nMag neurons in a cell-culture environment. We propose that the switch in receptor kinetics is an outcome of cellular interactions during a critical period that result in the long-term determination of receptor phenotype.