中缝背核GABA能神经元通过外侧缰核投射调控小鼠焦虑样行为  

The GABAergic projections from the dorsal raphe nucleus to lateral habenula regulates anxiety-like behaviors in mice

作　　者：吴慧敏 郭晓雨 李冰清 王丹 董海龙 WU Huimin;GUO Xiaoyu;LI Bingqing;WANG Dan;DONG Hailong(Shaanxi University of Chinese Medicine,Xianyang 712046;Department of Anesthesiology and Perioperative Medicine,Xijing Hospital,Air Force Medical University,Xi’an 710032,China)

机构地区：[1]陕西中医药大学,咸阳712046 [2]空军军医大学西京医院麻醉与围术期医学科,西安710032

出　　处：《神经解剖学杂志》2024年第2期179-186,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(82101343)。

摘　　要：目的:结合神经环路示踪及光遗传调控技术探讨中缝背核(DRN)中GABA能神经元投射至外侧缰核(LHb)神经末梢在焦虑行为中的调控作用。方法:将特异性逆向示踪病毒AAV retro-Ef1α-DIO-mCherry注射到Vgat-Cre小鼠LHb脑区,病毒表达后,采用多脑片玻片扫描显微镜成像,观察全脑范围LHb脑区接收GABA能神经投射的上游脑区分布情况。通过逆向示踪结果,将光遗传激活病毒AAV_(2/9)-Ef1a-DIO-ChR2-mCherry(ChR2组)和对照病毒AAV 2/9-Ef1a-DIO-mCherry(mCherry组)分别注射到Vgat-cre小鼠DRN核团,病毒表达后,使用光遗传激活DRN GABA神经元以及DRN GABA-LHb神经投射,观察其在焦虑样行为中的作用。结果:根据逆向示踪结果显示,中脑DRN脑区是LHb核团的GABA能神经投射上游脑区之一。光遗传刺激DRN^(GABA)神经元,与mCherry组相比,ChR2组在旷场(OFT)中的总距离以及在中央区运动时间、距离均显著增加;在高架十字迷宫(EPM)的开放臂停留时间和距离明显增加。与mCherry组相比,兴奋DRN GABA-LHb神经末梢,小鼠在OFT的中央区运动时间、距离和总运动距离显著增加;在EPM的开放臂停留时间显著延长。结论:特异性光激活DRN GABA神经元及DR^(GABA)-LHb神经末梢,均可显著改善小鼠焦虑样行为,为治疗焦虑、抑郁等精神疾病提供了新的思路和证据。Objective:Combined retrograde tracing with optogenetic methods,we are investigating the functional role of dorsal raphe nucleus(DRN)GABAergic neurons projecting to lateral habenula(LHb)terminals in anxiety-like behaviors.Methods:The specific retrograde tracing virus AAV retro-Ef1α-DIO-mCherry was injected into the LHb of Vgat-Cre mice.After the viral expression,Multi-brain slides scanning microscope imaging scan and observe the upstream distribution of GABAergic neural projection in LHb.By retrograde tracing,opto-activated virus AAV_(2/9)-Ef1a-DIO-ChR2-mCherry(ChR2 group)and control virus AAV 2/9-Ef1a-DIO-mCherry(mCherry group)were injected into the DRN of Vgat-cre mice respectively.Three weeks after virus expression,DRN^(GABA)neurons and the DRN ^(GABA)-LHb neural terminals were activated by optogenetic to observe their role in anxiety-like behaviors.Results:According to the results of retrograde tracing,the midbrain DRN is one of the major GABAergic neural projection brain areas in the LHb nucleus.Optogenetic stimulation of DRN^(GABA)neurons,compared with the mCherry group,the ChR2 group showed significantly longer total moving distance,central area moving time and distance in the open field test(OFT);In the elevated plus maze(EPM),the open arm moving time and distance was significantly increased.When DRN^(GABA)-LHb neural terminals were stimulated,compared with the mCherry group,the ChR2 group showed a significantly longer central zone moving time,distance and total moving distance in the OFT.During the elevated plus maze(EPM),the open arm moving time was significantly increased.Conclusion:The specific activation of the DRN^(GABA)neuron as well as the DRN^(GABA)-LHb neural projections showed that both significantly improved anxiety-like behaviors in mice.This provides new ideas and evidence for the treatment of anxiety,depression and other psychiatric disorders.

关 键 词：GABA能神经元 外侧缰核 中缝背核 神经环路 焦虑样行为 

分 类 号：R749.72[医药卫生—神经病学与精神病学]