Activation of nicotinic α7 acetylcholine receptor enhances long term potentation in wild type mice but not in APPswe/PS1ΔE9 mice

Amyloid β (Aβ) plays a central role in Alzheimer's disease (AD) and binds to the nicotinic α7 receptor (α7 nAChR). Little is known about the degree to which the binding of Aβ to the α7 nAChR influences the role of this receptor in long-term potentiation (LTP), however. We have studied the effect of the partial α7 nAChR agonist SSR180711 on hippocampal slice preparations from normal wild type (Wt) and APPswe/PS1ΔE9 transgenic (Tg) mice. In the hippocampal slices from the 6 months old Wt mice, the application of both nicotine (5 μM) and SSR180711 (300 nM) resulted in a significant enhancement of LTP expressed in area CA1. However, in the Tg mice the application of SSR180711 did not result in an increase in LTP beyond control levels. The amount of binding of the α7 nAChR ligand 125-I-α-bungarotoxin was not different between in Tg and Wt mice. These findings indicate that the α7 nAChR is functionally blocked in the hippocampal neurons, downstream of the α7 nAChR, and that this is likely due to an interaction between the receptor and Aβ, which leads to changes in LTP.

Research highlights▶ It is reported that a novel α7 acetylcholine receptor agonist SSR180711 elicit long term potentiation in vitro. ▶ The most interesting finding is that the effect of SSR180711 is only demonstrated in wild-type animals, but not in animals with accumulation of amyloid. ▶ It is shown that the number of binding sites is normal in transgene animals. ▶ These data support recent literature that interaction between α7 acetylcholine receptors and amyloids has functional consequences, and now directly focuses on a central element in memory formation.