α7nAchR/NMDAR coupling affects NMDAR function and object recognition

Molecular Brain
Shupeng LiFang Liu

Abstract

The α7 nicotinic acetylcholine receptor (nAchR) and NMDA glutamate receptor (NMDAR) are both ligand-gated ion channels permeable to Ca2+ and Na+. Previous studies have demonstrated functional modulation of NMDARs by nAchRs, although the molecular mechanism remains largely unknown. We have previously reported that α7nAchR forms a protein complex with the NMDAR through a protein-protein interaction. We also developed an interfering peptide that is able to disrupt the α7nAchR-NMDAR complex and blocks cue-induced reinstatement of nicotine-seeking in rat models of relapse. In the present study, we investigated whether the α7nAchR-NMDAR interaction is responsible for the functional modulation of NMDAR by α7nAchR using both electrophysiological and behavioral tests. We have found that activation of α7nAchR upregulates NMDAR-mediated whole cell currents and LTP of mEPSC in cultured hippocampal neurons, which can be abolished by the interfering peptide that disrupts the α7nAchR-NMDAR interaction. Moreover, administration of the interfering peptide in mice impairs novel object recognition but not Morris water maze performance. Our results suggest that α7nAchR/NMDAR coupling may selectively affect some aspects of learning and memory.

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Citations

Dec 9, 2014·Pharmacology, Biochemistry, and Behavior·Shaowen TianYong You
May 23, 2014·Frontiers in Cellular Neuroscience·Shupeng LiFang Liu
Mar 23, 2017·Frontiers in Cellular Neuroscience·JianGang WangChengBiao Lu
Oct 27, 2015·Journal of Proteomics·Hailong ZhangFang Liu
Jul 28, 2015·Biochemical Pharmacology·Qing Cheng, Jerrel L Yakel
Jan 4, 2019·Recent Patents on Anti-cancer Drug Discovery·Alessia SantoroPatrizia Russo
Oct 1, 2015·Pharmacological Reviews·Daniel BertrandDiana Donnelly-Roberts
Sep 3, 2019·Frontiers in Molecular Neuroscience·Rhys W LivingstoneJoanna M Williams
Jun 18, 2017·Frontiers in Immunology·Fabiana Maria das Graças Corsi-ZuelliCamila Marcelino Loureiro
Dec 19, 2020·The Journal of Cell Biology·Mar Petit-Pedrol, Laurent Groc

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Methods Mentioned

BETA
co-immunoprecipitation
dissection

Software Mentioned

Mini Analysis
Observer

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