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 hippocampal slices were used to observe the effects of a shorter synthetic fragment of beta-amyloid peptide (A beta31-35) on the induction of long-term potentiation (LTP) and the action of (-)huperzine A, a potent acetylcholinesterase (AChE) inhibitor on these processes was also observed. The results showed that: (1) 0.1 microM A beta31-35 suppressed the induction of LTP in a similar mode as the longer fragment A beta25-35, did, while they did not change the amplitude of the baseline population spike (PS); (2) when PSs were recorded separately in Mg2+-free medium, which unveils the N-methyl-D-aspartate (NMDA)-mediated responses, both A beta31-35 and A beta25-35 showed little effect on the components of multiple PSs; (3) two concentrations of 0.1 microM or 1.0 microM (-)huperzine A showed no effects on the PS amplitude while the latter could enhance the LTP and (4) co-administration of (-)huperzine A with 0.1 microM concentration could block most of the suppressive action induced by A beta31-35 or A beta25-35 upon the LTP. The results suggest that the shorter fragment A beta31-35, is long enough to suppress the 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.