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Bell-shaped D-serine actions on hippocampal long-term depression and spatial memory retrieval
Zhi Zhang1, Neng Gong, Wei Wang
1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Abstract:
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.
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