Nicotinic acetylcholine receptors contribute to learning-induced Metaplasticity in the hippocampus

Benjamin Becker, Eva M. Klein, Nadine Striepens, Yoan Mihov, Thomas E. Schlaepfer, Juergen Reul, Liesbet Goossens, Koen Schruers, Keith M. Kendrick, René Hurlemann

Research output: Contribution to journalArticlepeer-review

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 acetyl-choline 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 meman-tine or placebo and scanned on three subsequent runs of a hippo-campal 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.

Original languageEnglish (US)
Pages (from-to)986-997
Number of pages12
JournalJournal of cognitive neuroscience
Volume25
Issue number7
DOIs
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Cognitive Neuroscience

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