Distinctions among GABAA and GABAB responses revealed by calcium channel antagonists, cannabinoids, opioids, and synaptic plasticity in rat hippocampus.
Distinctions among GABAA and GABAB responses revealed by calcium channel antagonists, cannabinoids, opioids, and synaptic plasticity in rat hippocampus.
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钙通道拮抗剂、大麻素、阿片类药物和大鼠海马突触可塑性揭示了 GABAA 和 GABAB 反应的区别。
DOI：
10.1007/s00213-007-1040-4
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发表时间：
2008
影响因子：
3.4
通讯作者：
Alger,BradleyE
中科院分区：
文献类型：
--
作者：
Lafourcade,CarlosA;Alger,BradleyE
海马中间神经元释放γ-氨基丁酸（GABA）并产生快GABAA-和慢GABAB-抑制性突触后电位（IPSP）。GABABeIPSPs或产生它们的中间神经元的调节还不清楚。目的本研究验证以下假设：（1）所有的中间神经元都能启动GABA A和GABA B抑制性突触后电位：（2）GABA B反应对mGluR触发的内源性大麻素（eCB）介导的抑制性长时程抑制（iLTD）不敏感;（3）γ-氨基丁酸受体（GABA）反应是由表达μOR的中间神经元产生的，（4）γ-氨基丁酸受体（CB 1 R）依赖性反应和μ OR依赖性反应相互作用。高电阻微电极记录从锥体细胞，而interneurons被刺激extradecellular.ResultsGABABresponses被发现产生的interneurons释放GABA通过突触前N-型或P/Q-型钙通道，但他们是不敏感的抑制eCB或eCB介导的iLTD。GABABIPSP对μOR激动剂的抑制敏感，这表明GABAB反应的主要来源是表达μ OR的中间神经元群体。芋螺毒素中持续存在少量eCB-iLTD（eIPSP减少10%）。6/13的脑片eCB-iLTD被μOR激动剂阻断。CB 1 R或μOR激动剂将差异性地改变海马回路中的活性平衡。CB 1 R和μ OR介导的反应可以相互作用。
RationaleHippocampal interneurons release γ-aminobutyric acid (GABA) and produce fast GABAA- and slow GABAB-inhibitory postsynaptic potentials (IPSPs). The regulation of GABABeIPSPs or the interneurons that produce them are not well understood. In addition, while both μ-opioid receptors (μORs) and cannabinoid CB1R receptors (CB1Rs) are present on hippocampal interneurons, it is not clear how these two systems interact.ObjectivesThis study tests the hypotheses that: (1) all interneurons can initiate both GABAAand GABABinhibitory postsynaptic potentials; (2) GABABresponses are insensitive to mGluR-triggered, endocannabinoid (eCB)-mediated inhibitory long-term depression (iLTD); (3) GABABresponses are produced by interneurons that express μOR; and (4) CB1R-dependent and μOR-dependent response interact.Materials and methodsPharmacological and electrophysiological approaches were used in acute rat hippocampal slices. High resistance microelectrode recordings were made from pyramidal cells, while interneurons were stimulated extracellularly.ResultsGABABresponses were found to be produced by interneurons that release GABA via either presynaptic N-type or P/Q-type calcium channels but that they are insensitive to suppression by eCBs or eCB-mediated iLTD. GABABIPSPs were sensitive to suppression by a μOR agonist, suggesting a major source of GABABresponses is the μOR-expressing interneuron population. A small eCB-iLTD (10% eIPSP reduction) persisted in conotoxin. eCB-iLTD was blocked by a μOR agonist in 6/13 slices.ConclusionsGABABresponses cannot be produced by all interneurons. CB1R or μOR agonists will differentially alter the balance of activity in hippocampal circuits. CB1R- and μOR-mediated responses can interact.