Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain
Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain
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DOI：
10.1046/j.1460-9568.1999.00847.x
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发表时间：
1999-12-01
影响因子：
3.4
通讯作者：
Lutz, B
中科院分区：
文献类型：
--
作者：
Marsicano, G;Lutz, B
大麻素可以调节运动行为、学习和记忆、认知和疼痛感知。这些作用与大麻素受体1（CB 1）的表达和大脑中内源性大麻素的存在相关。在试图进一步了解大麻素的调节作用的机制，CB 1阳性神经元确定在小鼠前脑中的单细胞分辨率。我们进行了双重原位杂交研究，以检测结合谷氨酸脱羧酶65 k，神经肽胆囊收缩素（CCK），小清蛋白，calretinin和calbindin D28 k的mRNA的CB 1的mRNA。我们的研究结果表明，CB 1表达细胞可以分为不同的神经元亚群。在含有高水平或低水平CB 1 mRNA的神经元之间存在明显的区别。大多数CB 1高表达细胞是GABA能（γ-氨基丁酸）神经元，主要属于胆囊收缩素阳性和小清蛋白阴性类型的中间神经元（篮状细胞），在较低程度上，属于钙结合蛋白D28 k阳性中近端树突抑制性中间神经元。只有一小部分低表达CB 1的细胞是GABA能的。在海马、杏仁核和内嗅皮质区，CB 1 mRNA以低但显著的水平存在于许多非GABA能细胞中，这些细胞可以被认为是投射的主要神经元。因此，一个复杂的机制似乎是大麻素调节作用的基础。它们可能作用于主要的GABA能回路，也可能调节局部的GABA能抑制回路。CB 1与CCK高度共表达。众所周知，大麻素和CCK通常对行为和生理产生相反的影响。因此，我们认为大麻素和CCK之间可能存在假定的串扰，并将有助于更好地了解大麻素系统的生理学和药理学。
Cannabinoids can modulate motor behaviour, learning and memory, cognition and pain perception. These effects correlate with the expression of the cannabinoid receptor 1 (CB1) and with the presence of endogenous cannabinoids in the brain. In trying to obtain further insights into the mechanisms underlying the modulatory effects of cannabinoids, CB1-positive neurons were determined in the murine forebrain at a single cell resolution. We performed a double in situ hybridization study to detect mRNA of CB1 in combination with mRNA of glutamic acid decarboxylase 65k, neuropeptide cholecystokinin (CCK), parvalbumin, calretinin and calbindin D28k, respectively. Our results revealed that CB1-expressing cells can be divided into distinct neuronal subpopulations. There is a clear distinction between neurons containing CB1 mRNA either at high levels or low levels. The majority of high CB1-expressing cells are GABAergic (gamma-aminobutyric acid) neurons belonging mainly to the cholecystokinin-positive and parvalbumin-negative type of interneurons (basket cells) and, to a lower extent, to the calbindin D28k-positive mid-proximal dendritic inhibitory interneurons. Only a fraction of low CB1-expressing cells is GABAergic. In the hippocampus, amygdala and entorhinal cortex area, CB1 mRNA is present at low but significant levels in many non-GABAergic cells that can be considered as projecting principal neurons. Thus, a complex mechanism appears to underlie the modulatory effects of cannabinoids. They might act on principal glutamatergic circuits as well as modulate local GABAergic inhibitory circuits. CB1 is very highly coexpressed with CCK. It is known that cannabinoids and CCK often have opposite effects on behaviour and physiology. Therefore, we suggest that a putative cross-talk between cannabinoids and CCK might exist and will be relevant to better understanding of physiology and pharmacology of the cannabinoid system.