TY - JOUR
T1 - Nicotinic Acetylcholine Receptors Contribute to Learning-induced Metaplasticity in the Hippocampus
AU - Becker, Benjamin
AU - Klein, Eva M.
AU - Striepens, Nadine
AU - Mihov, Yoan
AU - Schlaepfer, Thomas E.
AU - Reul, Juergen
AU - Goossens, Liesbet
AU - Schruers, Koen
AU - Kendrick, Keith M.
AU - Hurlemann, Rene
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
U2 - 10.1162/jocn_a_00383
DO - 10.1162/jocn_a_00383
M3 - Article
C2 - 23469888
SN - 0898-929X
VL - 25
SP - 986
EP - 997
JO - Journal of Cognitive Neuroscience
JF - Journal of Cognitive Neuroscience
IS - 7
ER -