摘要
[目的]蓝斑(LC)去甲肾上腺素(NE)能神经元对嗅球(OB)有神经投射,但LC对OB兴奋性的调控作用未完全阐明。从在体和离体两个层面,探究NE对OB僧帽/簇状细胞(M/Ts)兴奋性的调控作用。[方法]在DBH-Cre小鼠LC注射AAV-DIO-ChR2-e YFP病毒并在OB埋置光电极,在体电生理记录M/Ts的动作电位,观察光激活(40 Hz/473 nm)OB的NE能神经元末梢对M/Ts自发和气味诱发反应的影响;同时采用离体膜片钳技术记录僧帽细胞的动作电位,研究NE对僧帽细胞兴奋性的直接影响。[结果]在体电生理结果显示:光激活OB的NE能神经末梢显著抑制了OB M/Ts自发(0.33±0.19 vs-0.48±0.28,P<0.01)和气味诱发(-0.0045±0.10 vs-0.81±0.13,P<0.0001)的电活动;进一步分析M/Ts气味诱发的反应,发现光激活OB的NE能神经末梢显著降低了M/Ts兴奋性反应的放电频率(4.81±0.42 vs 1.05±0.67,P<0.0001),却增强了抑制性反应的放电频率(-4.31±0.35 vs-3.02±0.50,P<0.0001)。离体膜片钳结果显示:NE增强了僧帽细胞放电频率(3.49±1.50 vs 9.47±2.65,P<0.05)。[结论]在体条件下,40 Hz光激活OB的NE能神经末梢减弱M/Ts自发和气味诱发的反应;而在离体水平上,NE增强了僧帽细胞的兴奋性。该文揭示了NE对OB兴奋性调控的复杂性。
[Objective]The locus coeruleus(LC)noradrenergic(NEergic)neurons project to olfactory bulb(OB).However,the precise manners in which LC modulate the excitability of OB remains unclear.This study aims to elucidate the regulatory effects of norepinephrine(NE)on the excitability of OB mitral/tufted cells(M/Ts)at both in vivo and vitro levels.[Method]In DBH-Cre mice,AAV-DIO-ChR2-eYFP virus was injected into the LC,followed by implantation of an optrode into OB.In vivo electrophysiology recordings was used to monitor the spikes of M/Ts,enabling us to assess the impact of optogenetic ac-tivation(40 Hz/473 nm)of OB NEergic terminals on spontaneous and odor-evoked responses in M/Ts.The patch-clamp re-cording was performed to record the action potential of mitral cells,and investigate the direct effect of NE on the excitability of mitral cells.[Result]In vivo electrophysiological data showed that optostimulation of OB NEergic terminals significantly inhibi-ted both spontaneous(0.33±0.19 vs-0.48±0.28,P<0.01)and odor-evoked(-0.0045±0.10 vs-0.81±0.13,P<0.0001)responses of M/Ts.For odor-evoked responses in M/Ts,optogenetic activation of OB NEergic terminals reduced the rate of single-unit spikes of excitatory responses(4.81±0.42 vs 1.05±0.67,P<0.0001)while enhanced the rate of single-unit spikes of inhibitory responses(-4.31±0.35 vs-3.02±0.50,P<0.0001).In contrast,in vitro patch-clamp experiments revealed that exposure NE significantly increased the firing frequency of mitral cells(3.49±1.50 vs 9.47±2.65,P<0.05).[Conclusion]Optogenetic activation(40 Hz)of OB NEergic terminals decreased the excitability of OB M/Ts in vi-vo,while NE enhanced the excitability of mitral cells in vitro,revealing the complex regulation role of NE in OB neuronal excit-ability.
作者
耿迟
李若晨
李姗
GENG Chi;LI Ruochen;LI Shan(Department of Biochemistry,School of Basic Medical Sciences,Xuzhou Medical University,Xuzhou 221000;Jiangsu Key Laboratory of Brain Disease Bioinformation,Xuzhou Medical University,Xuzhou 221000;National Demonstration Center for Experimental Basic Medical Science Education,Xuzhou Medical University,Xuzhou 221000;Department of Medical Affairs,The Seventh People's Hospital of Xuzhou,Xuzhou 221000,China)
出处
《生物技术》
2025年第6期698-703,共6页
Biotechnology
基金
江苏省“双创博士”(JSSCBS20211255)。
关键词
去甲肾上腺素
嗅球
僧帽/簇状细胞
40
Hz
蓝斑
动作电位
兴奋性反应
抑制性反应
norepinephrine
olfactory bulb
mitral/tufted cells
40 Hz
locus coeruleus
action potential
excitatory respon-ses
inhibitory responses
