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Open Access Highly Accessed Research article

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

Qiang Liu1, Yao Huang2, Jianxin Shen3, Scott Steffensen4 and Jie Wu135*

Author Affiliations

1 Divisions of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, 85013-4496, USA

2 Department of Obstetrics and Gynecology, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, 85004, USA

3 Department of Physiology, Shantou University Medical College, Guangdong, 515041, China

4 Department of Psychology, Brigham Young University Provo, Provo, UT, 84602, USA

5 Departments of Bioengineering, Arizona State University, Tempe, AZ, 85287, USA

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BMC Neuroscience 2012, 13:155  doi:10.1186/1471-2202-13-155

Published: 29 December 2012

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.

Keywords:
Nicotinic acetylcholine receptor; Amyloid; Hippocampal interneuron; Patch-clamp; Acutely dissociated neuron