Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides

Qiang Liu, Yao Huang, Jianxin Shen, Scott Steffensen, Jie Wu

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.Conclusion: 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.

Original languageEnglish (US)
Article number155
JournalBMC Neuroscience
Volume13
Issue number1
DOIs
StatePublished - Dec 29 2012
Externally publishedYes

Keywords

  • Acutely dissociated neuron
  • Amyloid
  • Hippocampal interneuron
  • Nicotinic acetylcholine receptor
  • Patch-clamp

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

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