Activity-dependent release and actions of endocannabinoids in the rat hypothalamic supraoptic nucleus
Activity-dependent release and actions of endocannabinoids in the rat hypothalamic supraoptic nucleus
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DOI：
10.1113/jphysiol.2005.097477
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发表时间：
2005-12-15
影响因子：
5.5
通讯作者：
Tasker, JG
中科院分区：
文献类型：
--
作者：
Di, S;Boudaba, C;Tasker, JG
外源性大麻素已被证明可以显著改变神经内分泌输出，预示着内源性大麻素作为重要的信号分子出现在稳态和生殖功能的神经内分泌控制中，包括应激反应、能量代谢和性腺调节。我们最近发现，下丘脑室旁核和视上核（SON）的大细胞和小细胞神经内分泌细胞通过释放内源性大麻素作为逆行信使调节谷氨酸的突触释放来响应糖皮质激素。在这里，我们直接显示的第一次，这两个主要的内源性大麻素，花生四烯酸（AEA）和2-花生四烯酸甘油（2-AG），被释放在一个活动依赖的方式从索马/树突的SON magnocellular神经元和抑制突触谷氨酸释放和突触后尖峰。大麻素再吸收阻断可增加SON区域活动依赖性内源性大麻素水平，并导致大细胞神经元突触驱动的尖峰活动受到抑制。总之，这些发现表明AEA和2-AG的活性依赖性释放导致谷氨酸释放的抑制，并且能够在大细胞神经元中形成尖峰活动。内源性大麻素对兴奋性突触输入的这种活性依赖性调节可能在确定刺激条件下大细胞神经元的尖峰模式特征中发挥作用。
Exogenous cannabinoids have been shown to significantly alter neuroendocrine output, presaging the emergence of endogenous cannabinoids as important signalling molecules in the neuroendocrine control of homeostatic and reproductive functions, including the stress response, energy metabolism and gonadal regulation. We showed recently that magnocellular and parvocellular neuroendocrine cells of the hypothalamic paraventricular nucleus and supraoptic nucleus (SON) respond to glucocorticoids by releasing endocannabinoids as retrograde messengers to modulate the synaptic release of glutamate. Here we show directly for the first time that both of the main endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), are released in an activity-dependent fashion from the soma/dendrites of SON magnocellular neurones and suppress synaptic glutamate release and postsynaptic spiking. Cannabinoid reuptake blockade increases activity-dependent endocannabinoid levels in the region of the SON, and results in the inhibition of synaptically driven spiking activity in magnocellular neurones. Together, these findings demonstrate an activity-dependent release of AEA and 2-AG that leads to the suppression of glutamate release and that is capable of shaping spiking activity in magnocellular neurones. This activity-dependent regulation of excitatory synaptic input by endocannabinoids may play a role in determining spiking patterns characteristic of magnocellular neurones under stimulated conditions.