Failure to detect changes in AMPA receptor binding after long-term potentiation

Abstract

Recent experimental evidence suggests that changes in (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/quisqualate receptor mediated currents account for the increase in synaptic responses known as long-term potentiation (LTP). These changes could occur in several parameters including receptor density, binding affinity or in the kinetics and conductance properties of the receptor channel. In this study we tested if LTP modifies the affinity or overall number of binding sites. Hippocampal slices were stimulated electrically in at least 12 locations in the stratum radiatum of CA1 in order to induce potentiation in a maximal number of Schaffer-collateral axons. Sections were then prepared from the middle of the slices, incubated with [3H]AMPA or [3H]CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and processed for autoradiography. To correct for variability among sections, binding in CA1 was expressed relative to that in the molecular layer of the dentate gyrus, which did not receive potentiation. No differences were observed in the absolute or relative amount of binding except for a small decrease of about 5% in [3H]AMPA binding that was not statistically significant. Although the percentage of synapses which were potentiated by our stimulation procedure cannot be determined with certainty, it is unlikely that an increase in the number or affinity of AMPA receptors could explain the 50% LTP effect typically observed in slices.