Bell-shaped D-serine actions on hippocampal long-term depression and spatial memory retrieval.
D-Serine, the endogenous coagonist of N-methyl-D-aspartate receptors (NMDARs), is considered to be an important gliotransmitter, and is essential for the induction of long-term potentiation. However, less is known about the role of D-serine in another form of synaptic plasticity, long-term depression (LTD). In this study, we found that exogenous D-serine regulated LTD in the hippocampal CA1 region in a "bell-shaped" concentration-dependent manner through regulating the function of NMDARs in the same manner, whereas endogenous D-serine was activity-dependently released and, in turn, contributed to the induction of LTD during low-frequency stimulation. Furthermore, impairing glial functions with sodium fluoroacetate (NaFAC) reduced the magnitude of LTD, which could be restored by exogenous D-serine, indicating that endogenous D-serine is mainly glia-derived during LTD induction. More interestingly, similar to the effects on LTD, exogenous D-serine enhanced spatial memory retrieval in the Morris water maze in a bell-shaped dose-dependent manner and rescued the NaFAC-induced impairment of memory retrieval, suggesting links between LTD and spatial memory retrieval. Our study thus provides direct evidence of the bell-shaped D-serine actions on hippocampal LTD and spatial memory retrieval, and underscores the importance of D-serine in synaptic plasticity, learning, and memory.
Zhang
Zhi
Z
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Gong
Neng
N
Wang
Wei
W
Xu
Lin
L
Xu
Tian-Le
TL
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology; D012694:Serine / Q000378:metabolism / Q000494:pharmacology*; D013028:Space Perception / Q000187:drug effects* / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine