Hardwiring the brain:: Endocannabinoids shape neuronal connectivity
Hardwiring the brain:: Endocannabinoids shape neuronal connectivity
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DOI：
10.1126/science.1137406
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发表时间：
2007-05-25
期刊：
影响因子：
56.9
通讯作者：
Harkany, Tibor
中科院分区：
文献类型：
--
作者：
Berghuis, Paul;Rajnicek, Ann M.;Harkany, Tibor
内源性大麻素信号在中枢神经系统发育过程中的作用尚不清楚。我们报道了CB 1大麻素受体（CB（1）Rs）在妊娠晚期啮齿类动物皮层中富含γ-氨基丁酸（GABA能）中间神经元的轴突生长锥。内源性大麻素通过激活RhoA触发CB 1 R内化和从丝状伪足消除，并诱导化学排斥和这些GABA能中间神经元的轴突生长锥的塌陷。类似地，内源性大麻素减少非洲爪蟾脊髓神经元的亲电性。这些发现，连同缺乏CB（1）Rs的皮质GABA能中间神经元的受损的靶选择，将内源性大麻素鉴定为轴突引导线索，并证明内源性大麻素信号传导调节体内突触发生和靶选择。
The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB1 cannabinoid receptors (CB(1)Rs) are enriched in the axonal growth cones of gamma-aminobutyric acid-containing ( GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB1R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB(1)Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.