Journal
NEUROPSYCHOPHARMACOLOGY
Volume 33, Issue 5, Pages 1004-1018Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.npp.1301486
Keywords
long-term depression; spatial reversal learning; NR2B receptor; Morris water maze; long-term potentiation; hippocampus
Categories
Ask authors/readers for more resources
The contributions of hippocampal long-term depression (LTD) to explicit learning and memory are poorly understood. Electrophysiological and behavioral studies examined the effects of modulating NMDA receptor-dependent LTD on spatial learning in the Morris water maze (MWM). The NMDA receptor co-agonist D-serine substantially enhanced NR2B-dependent LTD, but not long-term potentiation (LTP) or depotentiation, in hippocampal slices from adult wild type mice. Exogenous D-serine did not alter MWM acquisition, but substantially enhanced subsequent reversal learning of a novel target location and performance in a delayed-matching-to-place task. Conversely, an NR2B antagonist disrupted reversal learning and promoted perseveration. Endogenous synaptic D-serine likely saturates during LTP induction because exogenous D-serine rescued deficient LTP and MWM acquisition in GrinI(D481N) mutant mice having a lower D-serine affinity. Thus, D-serine may enhance a form of hippocampal NR2B-dependent LTD that contributes to spatial reversal learning. By enhancing this form of synaptic plasticity, D-serine could improve cognitive flexibility in psychiatric disorders characterized by perseveration of aberrant ideation or behaviors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available