Ionotropic NMDA Receptor Signaling Is Required for the Induction of Long-Term Depression in the Mouse Hippocampal CA1 Region
Ionotropic NMDA Receptor Signaling Is Required for the Induction of Long-Term Depression in the Mouse Hippocampal CA1 Region
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DOI：
10.1523/jneurosci.5419-13.2014
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发表时间：
2014-04-09
影响因子：
5.3
通讯作者：
O'Dell, Thomas J.
中科院分区：
文献类型：
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作者：
Babiec, Walter E.;Guglietta, Ryan;O'Dell, Thomas J.
以往的研究已经为NMDAR介导的突触后钙离子增加在诱导长期抑郁(LTD)中起关键作用的观点提供了强有力的支持。然而，这一观点最近受到了挑战，因为研究结果表明，LTD的诱导转而归因于一种离子通道非依赖的、代谢形式的NMDAR信号。因此，为了探索离子型和代谢型NMDAR信号在LTD中的作用，我们研究了改变细胞外钙水平或用MK-801阻断NMDAR通道离子通量对LTD和NMDAR信号在小鼠海马CA1区的影响。我们发现，成年小鼠海马区LTD的诱导对细胞外钙水平高度敏感，MK-801阻断了成年和未成熟小鼠海马区NMDAR依赖的LTD。此外，MK-801抑制NMDAR介导的p38-MAPK的激活和AMPAR GluA1亚基在LTD相关位点的去磷酸化。因此，我们的结果表明，LTD在海马CA1区的诱导依赖于电离性而不是代谢性的NMDAR信号。
Previous studies have provided strong support for the notion that NMDAR-mediated increases in postsynaptic Ca2+ have a crucial role in the induction of long-term depression (LTD). This view has recently been challenged, however, by findings suggesting that LTD induction is instead attributable to an ion channel-independent, metabotropic form of NMDAR signaling. Thus, to explore the role of ionotropic versus metabotropic NMDAR signaling in LTD, we examined the effects of varying extracellular Ca2+ levels or blocking NMDARchannel ion fluxes with MK-801 on LTD and NMDARsignaling in the mouse hippocampal CA1 region. We find that the induction of LTD in the adult hippocampus is highly sensitive to extracellular Ca2+ levels and that MK-801 blocks NMDAR-dependent LTD in the hippocampus of both adult and immature mice. Moreover, MK-801 inhibits NMDAR-mediated activation of p38-MAPK and dephosphorylation of AMPAR GluA1 subunits at sites implicated in LTD. Thus, our results indicate that the induction of LTD in the hippocampal CA1 region is dependent on ionotropic, rather than metabotropic, NMDAR signaling.