Requirement of α7 Nicotinic Acetylcholine Receptors for Amyloid Beta Protein-Induced Depression of Hippocampal Long-Term Potentiation in CA1 Region of Rats In Vivo

The high density of senile plaques with amyloid beta protein (A beta) and the loss of cholinergic neurons in the brain are the dominated pathological characteristics of Alzheimer's disease (AD). However, the active center of A beta, especially the cholinergic mechanism underlying the A beta neurotoxicity, is mostly unknown. This study examined the effects of different A beta fragments on hippocampal long-term potentiation (LTP) and investigated its probable alpha 7 nicotinic acetylcholine receptors (nAChRs) mechanism. The results show that: (1) intracerebroventicular injection of A beta 25-35 or A beta 31-35 significantly and similarly suppressed hippocampal LTP in CA1 region in rats; (2) choline, a selective alpha 7 nAChR agonist, did not affect the LTP induction but enhanced LTP suppression induced by A beta 31-35; and (3) methyllycaconitine, a specific alpha 7 nAChR antagonist, slightly suppressed hippocamal LTP but effectively prevented against A beta 31-35-induced LTP depression in the presence of A beta 31-35. These results indicate that: (1) the amino acid sequence 31-35 of the A beta peptide might be a shorter active sequence in the full length molecule; (2) alpha 7 nAChRs are required for the A beta-induced suppression of hippocampal LTP. Thus, this study not only provides a new insight into the mechanism by which A beta impairs synaptic plasticity but also strongly suggests that sequence 31-35 in A beta molecule and alpha 7 nAChRs in the brain might be potential therapeutic targets for the treatment of AD. Synapse 65: 1136-1143, 2011. (C) 2011 Wiley-Liss, Inc.