Suppressive action produced by β-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

Abstract

Extracellular recordings of field potential from CA1 region of rat hippocampal slices were used to observe the effects of a shorter synthetic fragment of β-amyloid peptide (A β 31–35) 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 μM Aβ 31–35 suppressed the induction of LTP in a similar mode as the longer fragment Aβ 25–35, did, while they did not change the amplitude of the baseline population spike (PS); (2) when PSs were recorded separately in Mg 2+ – free medium, which unveils the N-methyl- d-aspartate (NMDA)-mediated responses, both Aβ 31–35 and Aβ 25–35 showed little effect on the components of multiple PSs; (3) two concentrations of 0.1 μM or 1.0 μM (−)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 μM concentration could block most of the suppressive action induced by Aβ 31–35 or Aβ 25–35 upon the LTP. The results suggest that the shorter fragment Aβ 31–35, 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.