title: Nicotinic acetylcholine receptors contribute to learning-induced metaplasticity in the hippocampus.
abstract: Hippocampal learning is thought to induce metaplasticity, which can facilitate subsequent learning. Administered at single low doses, the N-methyl-d-aspartate-type glutamate receptor antagonist memantine predominantly blocks α7 nicotinic acetylcholine receptors (α7 nAChRs). Placebo-controlled administration of a single low dose of memantine in a pharmaco-fMRI experiment may thus help characterize the role of α7 nAChRs in hippocampal metaplasticity. We hypothesized that if α7 nAChRs contribute to learning-induced metaplasticity in the hippocampus, blockade of these receptors with low-dose memantine would selectively interfere with a facilitation of subsequent learning without impairing hippocampal learning per se. To specifically test this hypothesis, we devised a randomized controlled trial in which healthy volunteers were administered a 20-mg single oral dose of memantine or placebo and scanned on three subsequent runs of a hippocampal learning task. Our results indicate no discrepancies in behavioral learning between low-dose memantine- and placebo-treated participants in the first and second run of this task. In the third run, however, only the placebo-treated group showed facilitated behavioral learning, an effect paralleled by decreased neural responses in the hippocampal cornu ammonis region. Our findings suggest that blockade of α7 nAChRs selectively interfered with a learning-induced facilitation of subsequent learning while leaving unimpaired hippocampal learning per se. Taken together, our results provide support for a relevant contribution of α7 nAChRs to learning-associated metaplasticity in the hippocampus.
authors.affiliation: University of Bonn, Bonn, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Becker
authors.forename: Eva M
authors.initials: EM
authors.lastname: Klein
authors.forename: Nadine
authors.initials: N
authors.lastname: Striepens
authors.forename: Yoan
authors.initials: Y
authors.lastname: Mihov
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Schlaepfer
authors.forename: Juergen
authors.initials: J
authors.lastname: Reul
authors.forename: Liesbet
authors.initials: L
authors.lastname: Goossens
authors.forename: Koen
authors.initials: K
authors.lastname: Schruers
authors.forename: Keith M
authors.initials: KM
authors.lastname: Kendrick
authors.forename: René
authors.initials: R
authors.lastname: Hurlemann
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008433:Mathematics; D008559:Memantine / Q000494:pharmacology; D008570:Memory, Short-Term / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010364:Pattern Recognition, Visual / Q000187:drug effects; D010775:Photic Stimulation; D011978:Receptors, Nicotinic / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011978:Receptors, Nicotinic; D010100:Oxygen; D008559:Memantine