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臂旁核乙酰胆碱转移酶阳性神经元与小鼠恐惧记忆形成的关系 被引量:2

Relationship between choline acetyltransferase positive neurons in parabrachial nucleus and development of fear memory in mice
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摘要 目的评价臂旁核乙酰胆碱转移酶(ChAT)阳性神经元与小鼠恐惧记忆形成的关系。方法健康雄性ChAT-ires-cre小鼠18只,8~9周龄,体重22~25 g,采用随机数字表法分为3组(n=6):Cre依赖AAV-DIO-hM3Dq-mcherry(Gq)病毒/氯氮平-N-氧化物(CNO)组、Gq/生理盐水(NS)组和Cre依赖AAV-DIO-mcherry(mc)病毒/CNO组。Gq/CNO组小鼠臂旁核注射Gq病毒,3周后腹腔注射CNO 2 mg/kg;Gq/NS组小鼠臂旁核注射Gq病毒,3周后腹腔注射等容量生理盐水;mc/CNO组小鼠臂旁核注射mc病毒,3周后腹腔注射CNO 2 mg/kg。3组小鼠均于腹腔注射后30 min进行条件性恐惧实验。再进行全脑切片,观察病毒表达情况及ChAT阳性神经元投射脑区。结果与Gq/CNO组比较,Gq/NS组和mc/CNO组测试阶段僵立状态时间百分比升高(P<0.05)。Gq/mc病毒携带的荧光蛋白mcherry表达于小鼠臂旁核神经元,并与mcherry-ChAT存在共表达;ChAT阳性神经元的神经纤维投射到红核、黑质、中央杏仁核、丘脑前背侧核、终纹床核。结论臂旁核ChAT阳性神经元参与了恐惧记忆形成的调控,其被激活后会导致恐惧记忆受损,此调控可能是通过中央杏仁核实现的。 Objective To evaluate the relationship between choline acetyltransferase(ChAT)positive neurons in parabrachial nucleus and development of fear memory in mice.Methods Eighteen healthy male ChAT-ires-cre mice,aged 8-9 weeks,weighing 22-25 g,were divided into 3 groups(n=6 each)using a random number table method:Cre-dependent AAV-DIO-hM3Dq-mcherry(Gq)virus/clozapine-N-oxide(CNO)group(group Gq/CNO),Gq/normal saline(NS)group(group Gq/NS)and Cre-dependent AAV-DIO-mcherry(mc)virus/CNO group(group mc/CNO).Gq virus was injected into parabrachial nucleus,and CNO 2 mg/kg was injected intraperitoneally 3 weeks later in group Gq/CNO.Gq virus was injected into parabrachial nucleus,and the equal volume of normal saline was injected intraperitoneally 3 weeks later in group Gq/NS.In group mc/CNO,mc virus was injected into parabrachial nucleus,and CNO 2 mg/kg was injected intraperitoneally 3 weeks later.The fear conditioning test was performed at 30 min after intraperitoneal injection in all the 3 groups.The brains were then removed and sliced.The virus expression and areas of the brain projected by ChAT positive neurons were observed.Results Compared with group Gq/CNO,the percentage of freezing time was significantly increased during testing phase in Gq/NS and mc/CNO groups(P<0.05).Gq/mc virus carrying fluorescent protein mcherry was expressed in parabrachial nucleus and was co-expressed with mcherry-ChAT.The fibers of ChAT positive neurons projected to the red nucleus,substantia nigra,central amygdala,anterodorsal thalamic nucleus and bed nucleus of stria terminalis.Conclusion The ChAT positive neurons in parabrachial nucleus are involved in the regulation of the development of fear memory in mice,which can impair fear memory,and the regulation is carried out probably through central amygdala.
作者 杜肖南 田雪 严虹 Du Xiaonan;Tian Xue;Yan Hong(Department of Anesthesia,Central Hospital of Wuhan Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430014,China)
出处 《中华麻醉学杂志》 CAS CSCD 北大核心 2021年第8期965-969,共5页 Chinese Journal of Anesthesiology
基金 武汉市医学科研项目(WX19C29)。
关键词 臂旁核 胆碱O-乙酰转移酶 记忆 Parabrachial nucleus Choline O-acetyltransferase Memory
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