Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum.
Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum.
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DOI：
10.1523/jneurosci.4344-10.2010
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发表时间：
2010-11-10
期刊：
影响因子：
--
通讯作者：
Hansel C
中科院分区：
文献类型：
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作者：
Piochon C;Levenes C;Ohtsuki G;Hansel C
小脑生理学的一种经典观点认为，浦肯野细胞不表达功能性的N-甲基-D-天冬氨酸(NMDA)受体，因此，突触后NMDA受体不参与浦肯野细胞突触平行纤维(PF)处长时抑制(LTD)的诱导。最近的研究表明，功能性的NMDA受体在小鼠的浦肯野细胞突触的攀升纤维(CF)处表达，在出生后2个月左右达到完全表达水平。在这里，我们表明，在成熟的小鼠小脑LTD(由Pf和Cf成对激活引起)，但不能阻止Pf对浦肯野细胞的长时程增强(LTP；单独Pf刺激)突触被NMDA受体拮抗剂D-APV浴应用。当非竞争性NMDA通道阻断剂MK-801加入到贴片吸管生理盐水中时，LTD也被阻断，这表明突触后表达的NMDA受体是LTD诱导所必需的。使用共聚焦钙成像，我们发现在D-APV存在的情况下，树突棘中由CF引起的钙瞬变减少。这一观察结果证实了NMDA受体信号发生在CF突触，并提示在CF输入部位NMDA受体介导的钙瞬变可能参与了LTD的诱导。最后，我们对大鼠浦肯野细胞进行树突状膜片钳记录。当应用D-APV时，树突状记录的CF反应减少。综上所述，这些数据表明，突触后NMDA受体在CF突触至浦肯野细胞的发育后期表达与向NMDA受体依赖的LTD诱导机制的转换有关。
A classic view in cerebellar physiology holds that Purkinje cells do not express functional N-methyl-D-aspartate (NMDA) receptors and that, therefore, postsynaptic NMDA receptors are not involved in the induction of long-term depression (LTD) at parallel fiber (PF) to Purkinje cell synapses. Recently, it has been demonstrated that functional NMDA receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in mice, reaching full expression levels at about 2 months after birth. Here, we show that in the mature mouse cerebellum LTD (induced by paired PF and CF activation), but not long-term potentiation (LTP; PF stimulation alone) at PF to Purkinje cell synapses is blocked by bath application of the NMDA receptor antagonist D-APV. A blockade of LTD, but not LTP, was also observed when the non-competitive NMDA channel blocker MK-801 was added to the patch-pipette saline, suggesting that postsynaptically expressed NMDA receptors are required for LTD induction. Using confocal calcium imaging, we show that CF-evoked calcium transients in dendritic spines are reduced in the presence of D-APV. This observation confirms that NMDA receptor signaling occurs at CF synapses, and suggests that NMDA receptor-mediated calcium transients at the CF input site might contribute to LTD induction. Finally, we performed dendritic patch-clamp recordings from rat Purkinje cells. Dendritically recorded CF responses were reduced when D-APV was bath-applied. Together, these data suggest that the late developmental expression of postsynaptic NMDA receptors at CF synapses onto Purkinje cells is associated with a switch towards an NMDA receptor-dependent LTD induction mechanism.