Suppressive action produced by beta-amyloid peptide fragment 31-35 on long-term potentiation in rat hippocampus is N-methyl-D-aspartate receptor-independent: it's offset by (-)huperzine A

Extracellular recordings of field potential from CA1 region of rat hippocam pal slices were used to observe the effects of a shorter synthetic fragment of beta-amyloid peptide (A beta(31-35)) on the induction of long-term pote ntiation (LTP) and the action of (-)huperzine A, a potent acetylcholinester ase (AChE) inhibitor on these processes was also observed. The results show ed that: (1) 0.1 mu M A beta(31-35) suppressed the induction of LTP in a si milar mode as the longer fragment A beta(25-35), did, while they did not ch ange the amplitude of the baseline population spike (PS); (2) when PSs were recorded separately in Mg2+-free medium, which unveils the N-methyl-D-aspa rtate (NMDA)-mediated responses, both A beta(31-35) and A beta(25-35) showe d little effect on the components of multiple PSs; (3) two concentrations o f 0.1 mu M or 1.0 mu M (-)huperzine A showed no effects on the PS amplitude while the latter could enhance the LTP and (4) co-administration of (-)hup erzine A with 0.1 mu M concentration could block most of the suppressive ac tion induced by A beta(31-35) or A beta(25-35) upon the LTP. The results su ggest that the shorter fragment A beta(31-35), is long enough to suppress t he induction of LTP and these two fragments might suppress the induction of LTP through a NMDA receptor-independent pathway that involves cholinergic terminals in hippocampus. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.