CB1 Cannabinoid Receptor Expression in the Striatum: Association with Corticostriatal Circuits and Developmental Regulation.
CB1 Cannabinoid Receptor Expression in the Striatum: Association with Corticostriatal Circuits and Developmental Regulation.
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DOI：
10.3389/fphar.2012.00021
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发表时间：
2012
影响因子：
5.6
通讯作者：
Steiner H
中科院分区：
文献类型：
--
作者：
Van Waes V;Beverley JA;Siman H;Tseng KY;Steiner H
皮质纹状体回路介导目标导向行为的各个方面，对于基底神经节相关疾病至关重要。这些回路的活动由内源性大麻素系统通过刺激 CB1 大麻素受体来调节。 CB1 受体在纹状体的投射神经元和选择的中间神经元中高度表达，但不同纹状体区域（功能域）之间的表达水平差异很大。我们通过绘制大鼠皮质输入定义的纹状体区域中的 CB1 mRNA 水平，研究了特定皮质纹状体回路内的 CB1 受体表达。我们还评估了发育过程中纹状体中 CB1 表达的变化。我们的结果表明，CB1 表达在青少年 (P25) 中最高，然后逐渐降低到青少年 (P40) 和成人 (P70) 水平。在每个年龄段，CB1 受体主要在感觉运动纹状体区域表达，在联想和边缘区域表达相当低。此外，对于大多数皮质纹状体回路来说，皮质和纹状体表达水平之间存在反比关系。因此，具有高CB1表达的纹状体区域（感觉运动区域）倾向于接收来自低表达皮质区域的输入，而具有低表达的纹状体区域（联想/边缘区域）接收来自具有较高表达的皮质区域（内侧前额叶皮层）的输入。就 CB1 mRNA 水平反映受体功能而言，我们的研究结果表明不同发育阶段之间以及感觉运动和联想/边缘回路之间的 CB1 信号传导存在差异。 CB1受体表达在纹状体中的区域分布进一步表明，在感觉运动部分，CB1受体主要调节来自投射神经元局部轴突侧支的GABA输入，而在联想/边缘部分，CB1对来自中间神经元的GABA输入和谷氨酸输入的调节可能更重要。
Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains). We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25) and then progressively decreases toward adolescent (P40) and adult (P70) levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors) tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors) receive inputs from cortical regions with higher expression (medial prefrontal cortex). In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important.
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