Presynaptic, activity-dependent modulation of cannabinoid type 1 receptor-mediated inhibition of GABA release
Presynaptic, activity-dependent modulation of cannabinoid type 1 receptor-mediated inhibition of GABA release
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DOI：
10.1523/jneurosci.4587-05.2006
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发表时间：
2006-02-01
影响因子：
5.3
通讯作者：
Soltesz, I
中科院分区：
文献类型：
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作者：
Földy, C;Neu, A;Soltesz, I
内源性大麻素信号偶联活性依赖的突触后Ca2+水平上升，突触前GABA释放减少。在这里，我们从配对记录实验中提出证据，大麻素介导的GABA释放抑制取决于突触前中间神经元的放电速率。事后鉴定的胆囊收缩素阳性CA1细胞的低频动作电位在突触后锥体细胞中引发IPSCs，正如预期的那样，被外源性大麻素受体激动剂win55,215 -2 [R-(+)-（2,3-二氢-5-甲基-3-[（4-morpholinyl）甲基]pyrol[1,2,3-de]-1,4-苯并恶嗪-6-基）（1-萘基）甲烷单甲磺酸]在5 μ m下完全消除。当突触前放电频率增加到>= 20 Hz时，突触前篮细胞从大麻素激动剂诱导的GABA释放抑制中恢复。药理学实验表明，恢复的传输完全依赖于突触前n型Ca2+通道。此外，增加的突触前放电也可以克服甚至完全去极化诱导的抑制，这表明DSI的大小明显取决于篮状细胞的活性水平。这些结果揭示了内源性大麻素信号的活性依赖调节的新位点，并表明内源性大麻素介导的GABA释放抑制可能在不同的行为状态下有所不同。
Endocannabinoid signaling couples activity-dependent rises in postsynaptic Ca2+ levels to decreased presynaptic GABA release. Here, we present evidence from paired recording experiments that cannabinoid-mediated inhibition of GABA release depends on the firing rates of the presynaptic interneurons. Low-frequency action potentials in post hoc identified cholecystokinin-positive CA1 basket cells elicited IPSCs in the postsynaptic pyramidal cells that, as expected, were fully abolished by the exogenous application of the cannabinoid receptor agonist WIN55,212-2 [R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate] at 5 mu M. However, the presynaptic basket cells recovered from the cannabinoid agonist-induced inhibition of GABA release when the presynaptic firing rate was increased to >= 20 Hz. Pharmacological experiments showed that the recovered transmission was exclusively dependent on presynaptic N-type Ca2+ channels. Furthermore, the increased presynaptic firing could also overcome even complete depolarization-induced suppression of inhibition, indicating that the magnitude of DSI markedly depends on the activity levels of basket cells. These results reveal a new locus of activity-dependent modulation for endocannabinoid signaling and suggest that endocannabinoid-mediated inhibition of GABA release may differ in distinct behavioral states.