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, Rene Hurlemann*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-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 alpha 7 nicotinic acetylcholine receptors (alpha 7 nAChRs). Placebo-controlled administration of a single low dose of memantine in a pharmaco-fMRI experiment may thus help characterize the role of alpha 7 nAChRs in hippocampal metaplasticity. We hypothesized that if alpha 7 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 alpha 7 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 alpha 7 nAChRs to learning-associated metaplasticity in the hippocampus.
Original languageEnglish
Pages (from-to)986-997
JournalJournal of Cognitive Neuroscience
Volume25
Issue number7
DOIs
Publication statusPublished - Jul 2013

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