Long-term potentiation depends on release of D-serine from astrocytes.
Long-term potentiation depends on release of D-serine from astrocytes.
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作者：
突触传递的长时程增强（LTP）为研究记忆机制提供了一个实验模型。LTP的经典形式依赖于N-甲基-D-天冬氨酸受体（NMDAR），并且已经出现星形胶质细胞可以通过NMDAR共激动剂D-丝氨酸的Ca 2+依赖性释放来调节它们的激活。从神经胶质释放D-丝氨酸使LTP在文化和解释之间的相关性神经胶质覆盖的突触和LTP在视上核。然而，星形胶质细胞中的Ca 2+升高也可以释放其他信号分子，最突出的是谷氨酸、腺苷-5 ′-三磷酸和肿瘤坏死因子-α，而神经元本身可以合成和供应D-丝氨酸。此外，加载星形胶质细胞与外源性Ca 2+缓冲液不抑制LTP在海马CA 1区，和生理相关性的实验中的文化或强烈的外源性刺激施加到星形胶质细胞已受到质疑。因此，胶质细胞参与LTP诱导仍然存在争议。在这里，我们表明，在个别CA 1星形胶质细胞的钳位内部Ca 2+块LTP诱导附近的兴奋性突触通过减少NMDAR共激动剂位点的占用。这种LTP阻断可以被外源性D-丝氨酸或甘氨酸逆转，而单个星形胶质细胞中D-丝氨酸的耗尽或胞吐作用的破坏可以阻断局部LTP。因此，我们表明，钙依赖性释放的D-丝氨酸从星形胶质细胞控制NMDAR依赖的可塑性在附近发生的兴奋性突触成千上万。
Long-term potentiation (LTP) of synaptic transmission provides an experimental model for studying mechanisms of memory. The classical form of LTP relies on N-methyl-D-aspartate receptors (NMDARs), and it has emerged that astroglia can regulate their activation through Ca2+-dependent release of the NMDAR co-agonist D-serine. Release of D-serine from glia enables LTP in cultures and explains a correlation between glial coverage of synapses and LTP in the supraoptic nucleus. However, Ca2+ elevations in astroglia can also release other signalling molecules, most prominently glutamate, Adenosine-5′-triphosphate, and Tumor-Necrosis-Factor-α whereas neurons themselves can synthesise and supply D-serine. Furthermore, loading an astrocyte with exogenous Ca2+ buffers does not suppress LTP in hippocampal area CA1, and the physiological relevance of experiments in cultures or strong exogenous stimuli applied to astrocytes has been questioned. The involvement of glia in LTP induction thus remains controversial. Here we show that clamping internal Ca2+ in individual CA1 astrocytes blocks LTP induction at nearby excitatory synapses by reducing the occupancy of the NMDAR co-agonist sites. This LTP blockade can be reversed by exogenous D-serine or glycine whereas depletion of D-serine or disruption of exocytosis in an individual astrocyte blocks local LTP. We thus demonstrate that Ca2+-dependent release of D-serine from an astrocyte controls NMDAR-dependent plasticity in many thousands of excitatory synapses occurring nearby.
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影响因子：
4.8
作者：
Kartvelishvily, Elena;Shleper, Maria;Wolosker, Herman
通讯作者：
Wolosker, Herman
影响因子：
7.6
作者：
Duffy, Steven;Labrie, Viviane;Roder, John C.
通讯作者：
Roder, John C.
影响因子：
25
作者：
Oertner, TG;Sabatini, BL;Svoboda, K
通讯作者：
Svoboda, K
影响因子：
56.9
作者：
Pascual, O;Casper, KB;Haydon, PG
通讯作者：
Haydon, PG
DOI：
10.1073/pnas.0408483102
发表时间：
2005-04-12
影响因子：
11.1
作者：
Mothet, JP;Pollegioni, L;Baux, G
通讯作者：
Baux, G