Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum
Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum
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DOI：
10.1016/s0896-6273(02)00695-5
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发表时间：
2002-05-30
期刊：
影响因子：
16.2
通讯作者：
Regehr, WG
中科院分区：
文献类型：
--
作者：
Kreitzer, AC;Carter, AG;Regehr, WG
内源性大麻素在许多大脑区域充当逆行信使。这些可扩散的亲脂性分子由突触后细胞释放并调节突触前神经递质的释放。在这里，我们描述了一种介导内源性大麻素信号传导至远处抑制性突触的额外机制。小脑浦肯野细胞的去极化降低了附近中间神经元的放电率，而这种放电率的降低被大麻素受体拮抗剂 AM251 所阻断。大麻素受体激动剂 WIN55,212-2 也降低了中间神经元的放电率，这种抑制作用是由小钾电导的激活引起的。因此，去极化神经元树突释放的内源性大麻素可以抑制附近细胞的放电。由于中间神经元可以投射超过数百微米，这种对放电的抑制使细胞能够在远远超出内源性大麻素扩散限制的距离上调节突触输入。
Endocannabinoids serve as retrograde messengers in many brain regions. These diffusible lipophilic molecules are released by postsynaptic cells and regulate presynaptic neurotransmitter release. Here we describe an additional mechanism that mediates the spread of endocannabinoid signaling to distant inhibitory synapses. Depolarization of cerebellar Purkinje cells reduced the firing rate of nearby interneurons, and this reduction in firing was blocked by the cannabinoid receptor antagonist AM251. The cannabinoid receptor agonist WIN55,212-2 also reduced firing rates in interneurons, and this inhibition arose from the activation of a small potassium conductance. Thus, endocannabinoids released from the dendrites of depolarized neurons can lead to inhibition of firing in nearby cells. Because interneurons can project over several hundred micrometers, this inhibition of firing allows cells to regulate synaptic inputs at distances well beyond the limits of endocannabinoid diffusion.