Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission
Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission
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DOI：
10.1523/jneurosci.21-23-09506.2001
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发表时间：
2001-12-01
影响因子：
5.3
通讯作者：
Freund, TF
中科院分区：
文献类型：
--
作者：
Katona, I;Rancz, EA;Freund, TF
大麻素是世界上最流行的用于娱乐目的的非法药物。然而，到目前为止，它们改变情绪能力的神经生物学基础尚未阐明。在这里，我们报告CB1大麻素受体在某些杏仁核中高水平表达，特别是在外侧核和基底核中，但在其他核中不存在（例如，在中央核和内侧核中）。CB1蛋白的表达仅限于与大胆囊收缩素阳性细胞相对应的gaba能中间神经元的不同亚群。详细的电镜研究表明，CB1受体位于突触前，位于胆囊收缩素阳性轴突末端，与突触后靶点建立对称的gaba能突触。这种特殊的解剖定位的生理后果是通过全细胞膜片钳记录外侧核和基底核的主要细胞。CB1受体激动剂WIN 55,212-2和CP 55,940降低了GABA(A)受体介导的诱发和自发ipsc的振幅，而不依赖动作电位的微型ipsc则未受到显著影响。相比之下，CB1受体激动剂对改变大鼠中央核和CB1敲除小鼠基底核中IPSCs的振幅无效。这些结果表明大麻素针对特定杏仁核神经元网络中的特定元素，在那里它们突触前调节gaba能突触传递。我们提出，这些解剖和生理特征，CB1受体在几个前脑区域的特征，代表了内源性大麻素参与逆行突触信号传导的神经元底物，并可能解释大麻素暴露的一些情感相关行为影响。
Cannabinoids are the most popular illicit drugs used for recreational purposes worldwide. However, the neurobiological substrate of their mood-altering capacity has not been elucidated so far. Here we report that CB1 cannabinoid receptors are expressed at high levels in certain amygdala nuclei, especially in the lateral and basal nuclei, but are absent in other nuclei (e.g., in the central nucleus and in the medial nucleus). Expression of the CB1 protein was restricted to a distinct subpopulation of GABAergic interneurons corresponding to large cholecystokinin-positive cells. Detailed electron microscopic investigation revealed that CB1 receptors are located presynaptically on cholecystokinin-positive axon terminals, which establish symmetrical GABAergic synapses with their postsynaptic targets. The physiological consequence of this particular anatomical localization was investigated by whole-cell patch-clamp recordings in principal cells of the lateral and basal nuclei. CB1 receptor agonists WIN 55,212-2 and CP 55,940 reduced the amplitude of GABA(A) receptor-mediated evoked and spontaneous IPSCs, whereas the action potential-independent miniature IPSCs were not significantly affected. In contrast, CB1 receptor agonists were ineffective in changing the amplitude of IPSCs in the rat central nucleus and in the basal nucleus of CB1 knock-out mice. These results suggest that cannabinoids target specific elements in neuronal networks of given amygdala nuclei, where they presynaptically modulate GABAergic synaptic transmission. We propose that these anatomical and physiological features, characteristic of CB1 receptors in several forebrain regions, represent the neuronal substrate for endocannabinoids involved in retrograde synaptic signaling and may explain some of the emotionally relevant behavioral effects of cannabinoid exposure.