title: α7nAchR/NMDAR coupling affects NMDAR function and object recognition.
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.
authors.forename: Shupeng
authors.initials: S
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Nai
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Lipina
authors.forename: John C
authors.initials: JC
authors.lastname: Roder
authors.affiliation: Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, Ontario M5T 1R8, Canada. f.liu.a@utoronto.ca.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D010455:Peptides; D016194:Receptors, N-Methyl-D-Aspartate; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002794:Choline