Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations
Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations
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DOI：
10.1046/j.1460-9568.2000.00217.x
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发表时间：
2000-09-01
影响因子：
3.4
通讯作者：
Freund, TF
中科院分区：
文献类型：
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作者：
Hájos, N;Katona, I;Freund, TF
使用针对大麻素受体（CBI）的C-末端开发的新抗体，海马中的免疫染色显示了相对于先前报道的N-末端抗体的模式的额外轴突末端。由于这种抗体的灵敏度更高，在树突层显示对称（GABA能）突触的大比例的终扣也强烈的免疫反应性CB 1受体，作为轴突末梢的体周抑制细胞含有胆囊收缩素。然而，不对称的（神经元能）突触总是对CB 1呈阴性。为了研究突触前CB 1受体激活对海马抑制的影响，我们记录了主细胞的抑制性突触后电流（IPSC）。CB 1受体激动剂（WIN 55，212-2和CP 55，940）可抑制局部电刺激诱发的IPSC，而CB 1受体拮抗剂SR 141716 A可逆转或阻断这种抑制作用。动作电位驱动的IPSC，诱发的一个子集的中间神经元的药理刺激，也减少了CB 1受体激活。我们还研究了CB 1受体激动剂对Ca 2+非依赖性微型IPSC（mlPSC）的影响。两种激动剂对mlPSC的频率或振幅没有显著影响。CB 1受体激动剂CP 55，940可逆地降低了海马切片CA 3区海人酸诱导的同步γ振荡幅度，这与对IPSC的作用一致。我们使用CB 1（-/-）敲除小鼠来确认抗体和激动剂（WIN 55，212-2）作用的特异性。我们的结论是，突触前CB 1受体的激活减少钙依赖性GABA的释放，从而降低了海马网络振荡的功率。
Using a new antibody developed against the C-terminus of the cannabinoid receptor (CBI), the immunostaining in the hippocampus revealed additional axon terminals relative to the pattern reported previously with an N-terminus antibody. Due to a greater sensitivity of this antibody, a large proportion of boutons in the dendritic layers displaying symmetrical (GABAergic) synapses were also strongly immunoreactive for CB1 receptors, as were axon terminals of perisomatic inhibitory cells containing cholecystokinin. Asymmetrical (glutamatergic) synapses, however, were always negative for CB1. To investigate the effect of presynaptic CB1 receptor activation on hippocampal inhibition, we recorded inhibitory postsynaptic currents (IPSCs) from principal cells. Bath application of CB1 receptor agonists (WIN55,212-2 and CP55,940) suppressed IPSCs evoked by local electrical stimulation, which could be prevented or reversed by the CB1 receptor antagonist SR141716A. Action potential-driven IPSCs, evoked by pharmacological stimulation of a subset of interneurons, were also decreased by CB1 receptor activation. We also examined the effects of CB1 receptor agonists on Ca2+-independent miniature IPSCs (mlPSC). Both agonists were without significant effect on the frequency or amplitude of mlPSCs. Synchronous gamma oscillations induced by kainic acid in the CA3 region of hippocampal slices were reversibly reduced in amplitude by the CB1 receptor agonist CP 55,940, which is consistent with an action on IPSCs. We used CB1(-/-) knock-out mice to confirm the specificity of the antibody and of the agonist (WIN55,212-2) action. We conclude that activation of presynaptic CB1 receptors decreases Ca2+-dependent GABA release, and thereby reduces the power of hippocampal network oscillations.