2-Amino-4-phosphonobutyrate selectively eliminates late phases of long-term potentiation in rat hippocampus

The possible involvement of 2-amino-4-phosphonobutyrate (APB) recognition sites in mechanisms enabling the maintenance of long-term potentiation (LTP) was investigated in rat hippocampal slices. The action of D(-)- and L(+)-isomers of APB was tested on orthodromic EPSP and spike responses recorded extracellularly from CA1 pyramidal cells. If a moderate concentration (50 microM) of one or the other APB isomer was present during tetanization, posttetanic and early long-term potentiation developed nearly normally. However, from 2h onward LTP of both EPSP and spike potentiation was eliminated in an irreversible manner (8 h experiment). D-APB (L-isomer not tested) applied shortly after tetanization caused nearly the same delayed decline of LTP. No consistent effects of APB were seen in non-tetanized slices. Considering previous findings these data suggest that besides the obligatory NMDA receptor activation an APB-sensitive component expressed during and after tetanization is a necessary step for subsequent mechanisms enabling the late maintenance of LTP.