Increased small conductance calcium-activated potassium type 2 channel-mediated negative feedback on N-methyl-D-aspartate receptors impairs synaptic plasticity following context-dependent sensitization to morphine.
Increased small conductance calcium-activated potassium type 2 channel-mediated negative feedback on N-methyl-D-aspartate receptors impairs synaptic plasticity following context-dependent sensitization to morphine.
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DOI：
10.1016/j.biopsych.2013.04.026
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发表时间：
2014-01-15
影响因子：
10.6
通讯作者：
Moron, Jose A.
中科院分区：
文献类型：
--
作者：
Fakira, Amanda K.;Portugal, George S.;Carusillo, Brianna;Melyan, Zare;Moron, Jose A.
海马长时程增强（LTP）受损后，重复吗啡给药与新的背景配对。该过程产生运动敏化，其可通过阻断海马中的Ca 2+可渗透的2-氨基-3-（3-羟基-5-甲基-异恶唑-4-基）丙酸受体（AMPAR）来消除。然而，LTP受损的机制仍不清楚。在这里，我们调查的作用N-甲基-D-天冬氨酸受体（NMDARs），AMPARs和小电导钙激活钾2型（SK2）通道在LTP诱导后的上下文依赖性敏化吗啡。小鼠在自主活动（LMA）室中每12小时用生理盐水或递增剂量的吗啡（5、8、10和15 mg/kg）处理，一周后给予5 mg/kg吗啡的攻击剂量。激发后，取出海马以测定磷酸酶2A（PP 2A）活性、NMDAR和SK 2通道突触表达或进行电生理记录。受损的海马LTP，伴随着吗啡诱导的上下文依赖性敏化，不能通过阻断钙渗透AMPAR恢复。对吗啡的上下文依赖性敏化改变了海马NMDAR亚基的组成，并增强了SK2通道介导的NMDAR负反馈。增加PP 2A活动后观察到的上下文依赖性敏化表明，增强SK2通道对NMDAR的影响介导的增加SK2敏感性Ca 2+。最后，抑制SK2通道或PP 2A活性恢复LTP。我们的研究表明，SK2通道-NMDAR反馈回路在阿片诱导的海马可塑性损伤中起作用，并且通过PP 2A活性的增加发生SK2通道的正向调节。这进一步证明了SK通道在药物诱导的可塑性中发挥作用。
Hippocampal long term potentiation (LTP) is impaired following repeated morphine administration paired with a novel context. This procedure produces locomotor sensitization that can be abolished by blocking Ca2+-permeable 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid receptors (AMPARs) in the hippocampus. However, the mechanisms underlying LTP impairment remain unclear. Here, we investigate the role of N-methyl-D-aspartate receptors (NMDARs), AMPARs and small conductance Ca2+-activated potassium type 2 (SK2) channels in LTP induction after context-dependent sensitization to morphine. Mice were treated with saline or escalating doses of morphine (5, 8, 10 and 15 mg/kg) every 12 hours in a locomotor activity (LMA) chamber and a challenge dose of 5mg/kg morphine was given one week later. After the challenge the hippocampi were removed to assay phosphatase 2A (PP2A) activity, NMDAR and SK2 channel synaptic expression or to perform electrophysiological recordings. Impaired hippocampal LTP, which accompanied morphine-induced context-dependent sensitization, could not be restored by blocking Ca2+-permeable AMPARs. Context-dependent sensitization to morphine altered hippocampal NMDAR subunit composition and enhanced the SK2 channel-mediated negative feedback on NMDAR. Increased PP2A activity observed following context-dependent sensitization suggests that the potentiated SK2 channel effect on NMDAR was mediated by increased SK2 sensitivity to Ca2+. Finally, inhibition of SK2 channel or PP2A activity restored LTP. Our studies demonstrate that the SK2 channel-NMDAR feedback loop plays a role in opiate-induced impairment of hippocampal plasticity and that the positive modulation of SK2 channels occurs via increases in PP2A activity. This provides further evidence that SK channels play a role in drug-induced plasticity.
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影响因子：
5.3
作者：
McCutcheon, James E.;Wang, Xiaoting;Marinelli, Michela
通讯作者：
Marinelli, Michela
DOI：
10.1523/jneurosci.4022-09.2010
发表时间：
2010-02-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Foster KA;McLaughlin N;Edbauer D;Phillips M;Bolton A;Constantine-Paton M;Sheng M
通讯作者：
Sheng M
影响因子：
16.2
作者：
Gray JA;Shi Y;Usui H;During MJ;Sakimura K;Nicoll RA
通讯作者：
Nicoll RA
DOI：
10.1523/jneurosci.5703-08.2009
发表时间：
2009-05-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ishikawa M;Mu P;Moyer JT;Wolf JA;Quock RM;Davies NM;Hu XT;Schlüter OM;Dong Y
通讯作者：
Dong Y
影响因子：
25
作者：
Lin, Mike T.;Lujan, Rafael;Maylie, James
通讯作者：
Maylie, James