小鼠中枢组胺能神经元的特异性投射环路
|
摘要
目的探讨小鼠中枢组胺能神经元的特异性投射环路。方法将腺相关病毒(AAV)携带的人源绿色荧光蛋白作为示踪剂(AAV-hrGFP)微量注射至组胺脱羧酶Cre小鼠的结节乳头核,免疫荧光染色显示hrGFP的脑内分布,确定组胺能神经元的投射环路。结果绿色荧光蛋白hrGFP特异性表达在结节乳头核的组胺能神经元,并投射至大脑皮层、尾壳核、伏隔核、隔核、基底前脑、外侧下丘脑、杏仁核、终纹床核、丘脑、导水管周围灰质及臂旁核等脑区。结论中枢组胺能神经的特异性投射至脑内广泛区域,该研究结果有利于进一步阐明其调节觉醒、情绪等行为的神经功能环路。
Objective To identify the specific projections of the histaminergic neurons in the mouse brain.Methods The AAV-lox-Stop-hrGFP was stereotaxic injected into the tuberomammillary nucleus(TMN) in the histidine decarboxylase( HDC)-Cre mice. Then the projections of histaminergic TMN neurons were detected by the hrG FP fluorescence in the brain slices. Results The hrGFP-positive neurons were co-localized with the HDC immunoreactivity neurons,which were presented in the TMN in the mouse brain. The histaminergic TMN neurons innervated almost all central nervous system,including cerebral cortex,caudate-putman,nucleus accumbens,septal nucleus,basal forebrain,lateral hypothalamus,amygdala,bed nuclei of the stria terminalis,thalamus,periaqueductal gray and parabrachial nucleus. Conclusion The specific pathways of histaminergic TMN neurons are clarified,which may provide the foundation to reveal the neuronal circuits of histaminergic system in the regulation of wakefulness,mood and other behaviors.
Objective To identify the specific projections of the histaminergic neurons in the mouse brain.Methods The AAV-lox-Stop-hrGFP was stereotaxic injected into the tuberomammillary nucleus(TMN) in the histidine decarboxylase( HDC)-Cre mice. Then the projections of histaminergic TMN neurons were detected by the hrG FP fluorescence in the brain slices. Results The hrGFP-positive neurons were co-localized with the HDC immunoreactivity neurons,which were presented in the TMN in the mouse brain. The histaminergic TMN neurons innervated almost all central nervous system,including cerebral cortex,caudate-putman,nucleus accumbens,septal nucleus,basal forebrain,lateral hypothalamus,amygdala,bed nuclei of the stria terminalis,thalamus,periaqueductal gray and parabrachial nucleus. Conclusion The specific pathways of histaminergic TMN neurons are clarified,which may provide the foundation to reveal the neuronal circuits of histaminergic system in the regulation of wakefulness,mood and other behaviors.
引文
[1] Huang Z L,Mochizuki T,Qu W M,et al.Altered sleep-wake characteristics and lack of arousal response to H3 receptor antagonist in histamine H1 receptor knockout mice[J].Proc Natl Acad Sci U S A,2006,103(12):4687-92.
[2] He C,Luo F,Chen X,et al.Superficial layer-specific histaminergic modulation of medial entorhinal cortex required for spatial learning[J].Cereb Cortex,2016,26(4):1590-8.
[3] Haas H L,Sergeeva O A.,Selbach O.Histamine in the nervous system[J].Physiol Rev,2008,88(3):1183-41.
[4] Gautron L,Lazarus M,Scott M M,et al.Identifying the efferent projections of leptin-responsive neurons in the dorsomedial hypothalamus using a novel conditional tracing approach[J].J Comp Neurol,2010,518(11):2090-108.
[5] 丁丁,丁睿,吴芳,等.大鼠下丘脑腹外侧视前区和结节乳头体核的直接神经纤维投射研究[J].安徽医科大学学报,2014,49(10):1376-8.
[6] Zhang J P,Xu Q,Yuan X S,et al.Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation[J].Front Neuroanat,2013,7:43.
[7] Lantos T A,Gorcs T J,Palkovits M.Immunohistochemical mapping of neuropeptides in the premamillary region of the hypothalamus in rats[J].Brain Res Brain Res Rev,1995,20(2):209-49.
[8] 洪艳,施伍,梁悦,等.剥夺小鼠睡眠后促觉醒中枢TMN内小胶质细胞在睡眠-觉醒中的变化[J].安徽医科大学学报,2018,53(5):657-4.
[9] 刘天雅,洪宗元,曲卫敏,等.中枢组胺能神经系统调节睡眠-觉醒机制研究进展[J].药学学报,2011,46(3):247-52.
[10] Chu M,Huang Z L,Qu W M,et al.Extracellular histamine level in the frontal cortex is positively correlated with the amount of wakefulness in rats[J].Neurosci Res,2004,49(4):417-20.
[11] Wang Y Q,Takata Y,Li R,et al.Doxepin and diphenhydramine increased non-rapid eye movement sleep through blockade of histamine H1 receptors[J].Pharmacol Biochem Behav,2015,129:56-64.
[12] Oishi Y,Xu Q,Wang L,et al.Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice[J].Nat Commun,2017,8(1):734.
[2] He C,Luo F,Chen X,et al.Superficial layer-specific histaminergic modulation of medial entorhinal cortex required for spatial learning[J].Cereb Cortex,2016,26(4):1590-8.
[3] Haas H L,Sergeeva O A.,Selbach O.Histamine in the nervous system[J].Physiol Rev,2008,88(3):1183-41.
[4] Gautron L,Lazarus M,Scott M M,et al.Identifying the efferent projections of leptin-responsive neurons in the dorsomedial hypothalamus using a novel conditional tracing approach[J].J Comp Neurol,2010,518(11):2090-108.
[5] 丁丁,丁睿,吴芳,等.大鼠下丘脑腹外侧视前区和结节乳头体核的直接神经纤维投射研究[J].安徽医科大学学报,2014,49(10):1376-8.
[6] Zhang J P,Xu Q,Yuan X S,et al.Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation[J].Front Neuroanat,2013,7:43.
[7] Lantos T A,Gorcs T J,Palkovits M.Immunohistochemical mapping of neuropeptides in the premamillary region of the hypothalamus in rats[J].Brain Res Brain Res Rev,1995,20(2):209-49.
[8] 洪艳,施伍,梁悦,等.剥夺小鼠睡眠后促觉醒中枢TMN内小胶质细胞在睡眠-觉醒中的变化[J].安徽医科大学学报,2018,53(5):657-4.
[9] 刘天雅,洪宗元,曲卫敏,等.中枢组胺能神经系统调节睡眠-觉醒机制研究进展[J].药学学报,2011,46(3):247-52.
[10] Chu M,Huang Z L,Qu W M,et al.Extracellular histamine level in the frontal cortex is positively correlated with the amount of wakefulness in rats[J].Neurosci Res,2004,49(4):417-20.
[11] Wang Y Q,Takata Y,Li R,et al.Doxepin and diphenhydramine increased non-rapid eye movement sleep through blockade of histamine H1 receptors[J].Pharmacol Biochem Behav,2015,129:56-64.
[12] Oishi Y,Xu Q,Wang L,et al.Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice[J].Nat Commun,2017,8(1):734.