Functional Î±7Î²2 Nicotinic Acetylcholine Receptors Expressed In Hippocampal Interneurons Exhibit High Sensitivity To Pathological Level Of Amyloid Î² Peptides
Background: Î²-amyloid (AÎ²) accumulation is described as a hallmark of Alzheimer's disease (AD). AÎ² perturbs a number of synaptic components including nicotinic acetylcholine receptors containing Î±7 subunits (Î±7-nAChRs), which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric Î±7Î²2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute AÎ² exposure. To extend our previous work, we evaluated the expression and pharmacology of Î±7Î²2-nAChRs in hippocampal interneurons and their sensitivity to AÎ².Results: GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional Î±7Î²2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-Î²-erythroidine (DHÎ²E), a nAChR Î²2* subunit selective blocker, and Î±7 and Î²2 subunit interaction using immunoprecipitation assay. In addition, Î±7Î²2-nAChRs were sensitive to 1 nM oligomeric AÎ². Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice.Conclusion: These findings suggest that AÎ² modulation of cholinergic signaling in hippocampal GABAergic interneurons via Î±7Î²2-nAChRs could be an early and critical event in AÎ²-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD. Â© 2012 Liu et al.; licensee BioMed Central Ltd.
Digital Object Identifier (DOI)
Liu, Qiang; Huang, Yao; Shen, Jianxin; Steffensen, Scott; and Wu, Jie, "Functional Î±7Î²2 Nicotinic Acetylcholine Receptors Expressed In Hippocampal Interneurons Exhibit High Sensitivity To Pathological Level Of Amyloid Î² Peptides" (2012). Translational Neuroscience. 143.