title: Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides.
abstract: BACKGROUND
  β-amyloid (Aβ) accumulation is described as a hallmark of Alzheimer's disease (AD). Aβ perturbs a number of synaptic components including nicotinic acetylcholine receptors containing α7 subunits (α7-nAChRs), which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric α7β2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Aβ exposure. To extend our previous work, we evaluated the expression and pharmacology of α7β2-nAChRs in hippocampal interneurons and their sensitivity to Aβ.
  
  
  RESULTS
  GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional α7β2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-β-erythroidine (DHβE), a nAChR β2* subunit selective blocker, and α7 and β2 subunit interaction using immunoprecipitation assay. In addition, α7β2-nAChRs were sensitive to 1 nM oligomeric Aβ. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice.
  
  
  CONCLUSIONS
  These findings suggest that Aβ modulation of cholinergic signaling in hippocampal GABAergic interneurons via α7β2-nAChRs could be an early and critical event in Aβ-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.
authors.affiliation: Divisions of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013-4496, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Yao
authors.initials: Y
authors.lastname: Huang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Shen
authors.forename: Scott
authors.initials: S
authors.lastname: Steffensen
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D059330:GABAergic Neurons / Q000378:metabolism* / Q000502:physiology*; D055879:Gene Knock-In Techniques / Q000379:methods; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D016229:Amyloid beta-Peptides; D004079:Dihydro-beta-Erythroidine; D018733:Nicotinic Antagonists; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579166:Chrna7 protein, mouse; C075222:amyloid beta-protein (1-42)