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胆碱能上行通路的中脑边缘成分:电生理药理学研究。

Mesolimbic component of the ascending cholinergic pathways: electrophysiological-pharmacological study.

作者信息

Brudzynski S M, Kadishevitz L, Fu X W

机构信息

Department of Psychology, Brock University, St. Catharines, Ontario L2S 3A1, Canada.

出版信息

J Neurophysiol. 1998 Apr;79(4):1675-86. doi: 10.1152/jn.1998.79.4.1675.

DOI:10.1152/jn.1998.79.4.1675
PMID:9535938
Abstract

The cholinergic input from the pontomesencephalic cholinergic neurons to the diencephalic and basal forebrain structures has been implicated in a number of limbically controlled overt behaviors. The cellular mechanism by which the cholinergic terminals initiate behavioral manifestations is not clear. The objective of this study was to investigate the effects of the ascending cholinergic projection from the laterodorsal tegmental nucleus (LDT) on neuronal firing in the anterior hypothalamic-medial preoptic region (AHMP), known to be involved in agonistic behavior. Experiments were performed on urethan-anesthetized rats. Iontophoretic application of carbachol (CCh) into the vicinity of single cells in the AHMP caused a dose-dependent decrease in the mean firing rate of 83% of units and an increase in 10% of units. The inhibitory effect of CCh, but not the excitatory effect, was reversed by iontophoretic pretreatment with scopolamine. The inhibition of the firing rate was repeatable for the same dose of CCh and dose dependent. Electrical stimulation of neurons in the LDT caused a comparable, current-dependent decrease in the mean firing rate of AHMP neurons that also was reversed by pretreatment of neurons in the AHMP with scopolamine. The antagonizing effects of scopolamine were reversible with time. The same units in the AHMP that inhibited their firing to stimulation of the LDT also responded with a similar inhibition to local iontophoretic CCh. Finally, the fluorescent carbocyanine dye, 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide, (DiA), has been used as a retrograde axonal tracer and was injected into the recording sites immediately after the electrophysiological recordings. After 1 wk, DiA dye was found in numerous neurons in the LDT as shown by the fluorescence confocal microscopy. Results of the study suggest that LDT cholinergic neurons project and terminate in the AHMP and that their activation causes a decrease in the mean firing rate of the AHMP neurons. It is postulated that this inhibitory effect is implicated in the initiation of some of the behavioral patterns like defensive or alarm vocalization and behavioral inhibition.

摘要

脑桥中脑胆碱能神经元向间脑和基底前脑结构发出的胆碱能输入,与多种受边缘系统控制的明显行为有关。胆碱能终末引发行为表现的细胞机制尚不清楚。本研究的目的是探讨来自外侧背盖核(LDT)的上行胆碱能投射对下丘脑前部-内侧视前区(AHMP)神经元放电的影响,已知该区域参与争斗行为。实验在乌拉坦麻醉的大鼠身上进行。将卡巴胆碱(CCh)离子导入AHMP单个细胞附近,导致83%的单位平均放电率呈剂量依赖性下降,10%的单位放电率增加。CCh的抑制作用(而非兴奋作用)可被东莨菪碱离子导入预处理所逆转。相同剂量的CCh对放电率的抑制作用具有重复性且呈剂量依赖性。电刺激LDT中的神经元会导致AHMP神经元的平均放电率出现类似的、与电流相关的下降,这种下降也可被AHMP神经元用东莨菪碱预处理所逆转。东莨菪碱的拮抗作用会随时间可逆。AHMP中那些对LDT刺激放电受到抑制的相同单位,对局部离子导入CCh也有类似的抑制反应。最后,荧光碳青染料4-(4-(二十六烷基氨基)苯乙烯基)-N-甲基碘化吡啶鎓(DiA)被用作逆行轴突示踪剂,并在电生理记录后立即注入记录部位。1周后,通过荧光共聚焦显微镜观察发现,LDT中有许多神经元含有DiA染料。研究结果表明,LDT胆碱能神经元投射并终止于AHMP,其激活会导致AHMP神经元的平均放电率下降。据推测,这种抑制作用与某些行为模式的启动有关,如防御性或警报性发声以及行为抑制。

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