Liu_2012_BMC.Neurosci_13_155

BACKGROUND: beta-amyloid (Abeta) accumulation is described as a hallmark of Alzheimer's disease (AD). Abeta perturbs a number of synaptic components including nicotinic acetylcholine receptors containing alpha7 subunits (alpha7-nAChRs), which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric alpha7beta2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Abeta exposure. To extend our previous work, we evaluated the expression and pharmacology of alpha7beta2-nAChRs in hippocampal interneurons and their sensitivity to Abeta.
RESULTS: GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional alpha7beta2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-beta-erythroidine (DHbetaE), a nAChR beta2* subunit selective blocker, and alpha7 and beta2 subunit interaction using immunoprecipitation assay. In addition, alpha7beta2-nAChRs were sensitive to 1 nM oligomeric Abeta. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice. CONCLUSION: These findings suggest that Abeta modulation of cholinergic signaling in hippocampal GABAergic interneurons via alpha7beta2-nAChRs could be an early and critical event in Abeta-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.