Ionotropic NMDA Receptor Signaling Is Required for the Induction of Long-Term Depression in the Mouse Hippocampal CA1 Region

被引：59

作者：

Babiec, Walter E. ^{[1
]}

Guglietta, Ryan ^{[2
]}

Jami, Shekib A. ^{[3
]}

Morishita, Wade ^{[5
]}

Malenka, Robert C. ^{[5
]}

O'Dell, Thomas J. ^{[1
,4
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Interdept PhD Program Neurosci, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Mol Cellular & Integrat Physiol PhD Program, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, UCLA Integrat Ctr Learning & Memory, Los Angeles, CA 90095 USA

[5] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Nancy Pritzker Lab, Palo Alto, CA 94304 USA

来源：

JOURNAL OF NEUROSCIENCE | 2014年 / 34卷 / 15期

关键词：

hippocampus; long-term depression; MK-801; NMDA receptor; AREA CA1; SYNAPTIC DEPRESSION; RAT HIPPOCAMPUS; PROTEIN-KINASE; AMYLOID-BETA; ACTIVATION; DEPHOSPHORYLATION; POTENTIATION; MECHANISMS; SUBUNIT;

D O I：

10.1523/JNEUROSCI.5419-13.2014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

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.

引用

页码：5285 / 5290

页数：6

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