Bell-shaped D-serine actions on hippocampal long-term depression and spatial memory retrieval.
Bell-shaped D-serine actions on hippocampal long-term depression and spatial memory retrieval.
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DOI：
10.1093/cercor/bhn008
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发表时间：
2008-10
期刊：
影响因子：
3.7
通讯作者：
Zhi Zhang;Neng Gong;Wei Wang;Line Xu;Tian-Le Xu
中科院分区：
文献类型：
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作者：
Zhi Zhang;Neng Gong;Wei Wang;Line Xu;Tian-Le Xu
d -丝氨酸是n -甲基- d -天冬氨酸受体（NMDARs）的内源性凝聚剂，被认为是一种重要的胶质递质，是诱导长时程增强所必需的。然而，d -丝氨酸在另一种形式的突触可塑性，长期抑制（LTD）中的作用知之甚少。在本研究中，我们发现外源性d -丝氨酸通过同样的方式调节NMDARs的功能，以“钟形”浓度依赖性的方式调节海马CA1区域的LTD，而内源性d -丝氨酸则是活性依赖性的释放，反过来，在低频刺激时促进LTD的诱导。此外，氟乙酸钠（NaFAC）对胶质细胞功能的损害降低了LTD的大小，而外源性d -丝氨酸可以恢复LTD，这表明内源性d -丝氨酸在LTD诱导过程中主要来自胶质细胞。更有趣的是，与对LTD的影响相似，外源性d -丝氨酸以剂量依赖的钟形方式增强Morris水迷宫中的空间记忆检索，并挽救nafac诱导的记忆检索损伤，提示LTD与空间记忆检索之间存在联系。因此，我们的研究为钟形d -丝氨酸对海马LTD和空间记忆检索的作用提供了直接证据，并强调了d -丝氨酸在突触可塑性、学习和记忆中的重要性。
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.