Zhang Zhi, Gong Neng, Wang Wei, Xu Lin, Xu Tian-Le
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Cereb Cortex. 2008 Oct;18(10):2391-401. doi: 10.1093/cercor/bhn008. Epub 2008 Feb 14.
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.
D-丝氨酸是N-甲基-D-天冬氨酸受体（NMDARs）的内源性协同激动剂，被认为是一种重要的胶质递质，对长时程增强的诱导至关重要。然而，关于D-丝氨酸在另一种形式的突触可塑性——长时程抑制（LTD）中的作用，人们了解较少。在本研究中，我们发现外源性D-丝氨酸通过以相同方式调节NMDARs的功能，以“钟形”浓度依赖性方式调节海马CA1区的LTD，而内源性D-丝氨酸则以活动依赖性方式释放，进而在低频刺激期间促进LTD的诱导。此外，用氟乙酸钠（NaFAC）损害胶质细胞功能会降低LTD的幅度，外源性D-丝氨酸可使其恢复，这表明内源性D-丝氨酸在LTD诱导过程中主要来源于胶质细胞。更有趣的是，与对LTD的影响类似，外源性D-丝氨酸以钟形剂量依赖性方式增强了Morris水迷宫中的空间记忆检索，并挽救了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，我们的研究提供了直接证据，证明D-丝氨酸对海马LTD和空间记忆检索具有钟形作用，并强调了D-丝氨酸在突触可塑性、学习和记忆中的重要性。
