Wang Xueying, Liu Peipei, Ma Lan, Wang Feifei
State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, China.
Neuroreport. 2019 May 22;30(8):592-599. doi: 10.1097/WNR.0000000000001254.
The endogenous opioid system is of great importance to normal brain functions. Opiate acts on GABAergic cells in both the ventral tegmental area and the nucleus accumbens to exert psychological effects. However, the effects of opioid signal transduction on the morphology of GABAergic interneurons (INs) of the medial prefrontal cortex (mPFC), a brain region critical for motivational and addictive behaviors, are unclear. By fluorescent dye injection and morphological reconstruction, we found that the total dendrite length and dendritic complexity of both parvalbumin (PV) INs and somatostatin (SST) INs in mPFC were significantly increased after chronic morphine administration, and such changes lasted 7 days after morphine abstinence. We then downregulated the endogenous μ-opioid and δ-opioid receptors (ORs) in the mPFC by adeno-associated virus-mediated shRNA expression. Results showed that downregulating either μ-OR or δ-OR decreased the total dendrite length and dendritic complexity of SST-INs, whereas downregulating neither μ-OR nor δ-OR affected the morphology of PV-INs. Furthermore, δ-OR but not μ-OR knockdown impaired the dendritic structure of SST-INs in the mice upon single morphine administration. Our findings indicate the differential roles of endogenous ORs in the dendritic remodeling of SST-INs and PV-INs in mPFC.
内源性阿片系统对正常脑功能至关重要。阿片类药物作用于腹侧被盖区和伏隔核中的γ-氨基丁酸(GABA)能细胞,以发挥心理效应。然而,阿片信号转导对内侧前额叶皮质(mPFC)中GABA能中间神经元(INs)形态的影响尚不清楚,而mPFC是对动机和成瘾行为至关重要的脑区。通过荧光染料注射和形态重建,我们发现慢性吗啡给药后,mPFC中小清蛋白(PV)INs和生长抑素(SST)INs的总树突长度和树突复杂性均显著增加,且这些变化在吗啡戒断后持续7天。然后,我们通过腺相关病毒介导的短发夹RNA(shRNA)表达下调mPFC中的内源性μ-阿片受体和δ-阿片受体(ORs)。结果显示,下调μ-OR或δ-OR均会降低SST-INs的总树突长度和树突复杂性,而下调μ-OR和δ-OR均不影响PV-INs的形态。此外,单次给予吗啡后,敲低δ-OR而非μ-OR会损害小鼠中SST-INs的树突结构。我们的研究结果表明内源性ORs在mPFC中SST-INs和PV-INs的树突重塑中具有不同作用。