Effects of mu-opioid receptor modulation on GABAB receptor synaptic function in hippocampal CA1.
Effects of mu-opioid receptor modulation on GABAB receptor synaptic function in hippocampal CA1.
复制标题
mu-阿片受体调节对海马 CA1 区 GABAB 受体突触功能的影响。
DOI：
10.1152/jn.01179.2006
复制
发表时间：
2007
影响因子：
2.5
通讯作者：
McQuiston,ARory
中科院分区：
文献类型：
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作者：
McQuiston,ARory
μ-阿片受体（MORs）的激活改变海马CA1区的信息编码、突触可塑性和空间记忆。在CA 1中，MORs通过仅抑制GABA释放到GABA A和GABA B受体上而起作用。莫尔激活可通过抑制GABA A受体的突触激活来促进CA 1树突层中的兴奋性输入。在这项研究中，我们使用电压敏感染料成像显示，莫尔激活的莫尔激动剂DAMGO抑制GABA抑制性突触后电位在所有层的CA 1。当在荷包牡丹碱（50 μ M）存在下以20 Hz的5个脉冲刺激东方层（SO）、放射层（SR）或腔隙分子层（SLM）的兴奋性输入时，DAMGO（1 μ M）在增加最后一个兴奋性事件的幅度方面最有效。这种作用可被莫尔拮抗剂CTOP（1 μ M）逆转，并被GABA受体激动剂CGP 55845（10 μ M）阻断。与CGP 55845的作用相比，DAMGO在增加后期兴奋性事件的振幅方面效果较差。DAMGO在增加SLM中兴奋性输入的幅度方面相对无效，但当它们传播到皮层（SP）时，对兴奋性事件具有显著更大的影响。当刺激SR时，DAMGO在增加SLM的兴奋幅度方面效果最差，而在SP和SO中效果最好。最后，DAMGO是同样有效的增加兴奋性活动幅度在所有层的CA 1后，刺激SO。因此，莫尔抑制CA1所有层中的GABA突触超极化，并最有效地促进CA1输出层中的兴奋性活动。
Activation of μ-opioid receptors (MORs) alters information coding, synaptic plasticity, and spatial memory in hippocampal CA1. In CA1, MORs act by inhibiting GABA release onto both GABAAand GABABreceptors exclusively. MOR activation can facilitate excitatory inputs in CA1 dendritic layers by inhibiting synaptic activation of GABAAreceptors. In this study, we use voltage-sensitive dye imaging to show that MOR activation by the MOR agonist DAMGO suppressed GABABinhibitory postsynaptic potentials in all layers of CA1. When stimulating excitatory input in stratum oriens (SO), stratum radiatum (SR), or stratum lacunosum-moleculare (SLM) with five pulses at 20 Hz in the presence of bicuculline (50 μM), DAMGO (1 μM) was most effective at increasing the amplitude of the last excitatory event. This effect was reversed by the MOR antagonist CTOP (1 μM) and occluded by the GABABreceptor agonist CGP 55845 (10 μM). DAMGO was less effective at increasing the amplitude of later excitatory events compared with the effect of CGP 55845. DAMGO was relatively ineffective at increasing the amplitude of excitatory inputs in SLM but had significantly greater effects on excitatory events as they propagated to stratum pyramidale (SP). When stimulating in SR, DAMGO was least effective at increasing excitatory amplitudes in SLM and most effective in SP and SO. Finally, DAMGO was equally effective at increasing excitatory activity amplitudes in all layers of CA1 after stimulating in SO. Therefore MOR suppresses GABABsynaptic hyperpolarizations in all layers of CA1 and most effectively facilitates excitatory activity in CA1 output layers.