MGE-derived nNOS+ interneurons promote fear acquisition in nNOS-/- mice.
MGE-derived nNOS+ interneurons promote fear acquisition in nNOS-/- mice.
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DOI：
10.1016/j.bbrc.2017.09.158
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发表时间：
2017-12
影响因子：
3.1
通讯作者：
Lin Zhang;Hong-Jin Yuan;Bo Cao;Cheng-Cheng Kong-Cheng;Fang Yuan;Jun Li;Huanyu Ni;Haiyin Wu;Lei Chang;Yan Liu;Chunxia Luo
中科院分区：
文献类型：
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作者：
Lin Zhang;Hong-Jin Yuan;Bo Cao;Cheng-Cheng Kong-Cheng;Fang Yuan;Jun Li;Huanyu Ni;Haiyin Wu;Lei Chang;Yan Liu;Chunxia Luo
神经元型一氧化氮合酶（neuronalnitricoxidesynthase，nNOS）1主要负责中枢神经系统（centralnervoussystem，CNS）2中NO的释放，在多种生理功能中发挥重要作用。然而，nNOS+中间神经元在恐惧学习中的功能还没有得到太多的探讨。在这里，我们专注于内侧神经节隆起（MGE）3衍生的nNOS+中间神经元在恐惧学习。为了确定nNOS+中间神经元的来源，我们在体外培养神经元从MGE，皮质，外侧神经节隆起（LGE）4，尾神经节隆起（CGE）5和视前区（POA）6。结果表明，MGE含有最丰富的nNOS+中间神经元前体。E12.5胚胎的供体细胞中nNOS阳性神经元的阳性率最高，而E11.5、E12、E13、E13.5和E14胚胎的供体细胞中nNOS阳性神经元的阳性率最低。此外，这些来自E12.5胚胎的细胞在培养10天后显示出长轴突和丰富的树突，表明移植后在宿主神经回路中分散和整合的能力。为了研究MGE衍生的nNOS+中间神经元在恐惧学习中的作用，将供体MGE细胞移植到nNOS敲除（nNOS−/−）或野生型小鼠的齿状回（DG）7中。结果表明，移植MGE细胞促进了nNOS−/−的获得，而不是野生型小鼠，这表明nNOS+神经元在恐惧获得中的重要性。此外，我们将来自nNOS−/−小鼠或野生型小鼠的MGE细胞移植到nNOS−/-小鼠的DG中，发现只有来自野生型小鼠的MGE细胞而不是nNOS−/−小鼠的MGE细胞挽救了nNOS−/−小鼠的获得缺陷，进一步证实了nNOS+神经元在恐惧学习中的积极作用。
Neuronal nitric oxide synthase (nNOS)1, mainly responsible for NO release in central nervous system (CNS)2, plays a significant role in multiple physiological functions. However, the function of nNOS+interneurons in fear learning has not been much explored. Here we focused on the medial ganglionic eminences (MGE)3-derived nNOS+interneurons in fear learning. To determine the origin of nNOS+interneurons, we cultured neurons in vitro from MGE, cortex, lateral ganglionic eminence (LGE)4, caudal ganglionic eminences (CGE)5and preoptic area (POA)6. The results showed that MGE contained the most abundant precursors of nNOS+interneurons. Moreover, donor cells from E12.5 embryos demonstrated the highest positive rate of nNOS+interneurons compared with other embryonic periods (E11.5, E12, E13, E13.5 and E14). Additionally, these cells from E12.5 embryos showed long axonal and abundant dendritic arbors after 10 days culture, indicating the capability to disperse and integrate in host neural circuits after transplantation. To investigate the role of MGE-derived nNOS+interneurons in fear learning, donor MGE cells were transplanted into dentate gyrus (DG)7of nNOS knock-out (nNOS−/−) or wild-type mice. Results showed that the transplantation of MGE cells promoted the acquisition of nNOS−/−but not the wild-type mice, suggesting the importance of nNOS+neurons in fear acquisition. Moreover, we transplanted MGE cells from nNOS−/−mice or wild-type mice into DG of the nNOS−/-mice and found that only MGE cells from wild-type mice but not the nNOS−/−mice rescued the deficit in acquisition of the nNOS−/−mice, further confirming the positive role of nNOS+neurons in fear learning.