D-Serine augments NMDA-NR2B receptor-dependent hippocampal long-term depression and spatial reversal learning

作者：Duffy Steven^*; Labrie Viviane; Roder John C

来源：Neuropsychopharmacology, 2008, 33(5): 1004-1018.

DOI：10.1038/sj.npp.1301486

• long-term depression
• spatial reversal learning
• NR2B receptor
• Morris water maze
• long-term potentiation
• hippocampus

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.

• 出版日期2008-4
• 单位河北医科大学