Chergui K, Nomikos G G, Mathé J M, Gonon F, Svensson T H
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Neuroscience. 1996 May;72(1):141-56. doi: 10.1016/0306-4522(95)00513-7.
The present study was designed to evaluate the postsynaptic functional consequences of different presynaptic activity patterns in midbrain dopamine systems using electrical stimulation of the rat medial forebrain bundle and subsequent determination of c-fos expression, used as a marker for neuronal activation, in dopamine target areas, by means of Fos immunohistochemistry. Nerve terminal dopamine release evoked by electrical stimulation of the medial forebrain bundle was monitored in the same animals using in vivo voltammetry. A 5 Hz stimulation consisting of 60 trains of five pulses and lasting 1 min was applied to the medial forebrain bundle. This stimulation was repeated 15 times every 3 min. Its pattern was defined by the interpulse interval which was either 70 ms or 200 ms for burst or regularly spaced stimulation, respectively. Our results show that burst stimulation of the medial forebrain bundle, which increase release of dopamine in target areas, increases the basal Fos-like immunoreactivity in the stimulated hemisphere, while regular stimulation does not affect expression of this protein. Moreover, the increase in Fos-like immunoreactivity induced by burst stimulation is restricted to limbic related structures, i.e. nucleus accumbens shell and intermediate aspect of the lateral septum, and the major island of Calleja, but is not observed in motor related structures (nucleus accumbens core and striatum). Pretreatment with the D1 dopamine receptor antagonist, SCH23390 (0.1 mg/kg, i.p.), blocked the increase in Fos-like immunoreactivity induced by burst stimulation of the medial forebrain bundle, suggesting a role for these receptors in the observed effects. Pretreatment with the 5-hydroxytryptamine2A/2C receptor antagonist ritanserin (0.4 mg/kg, i.p.) did not affect the increase in Fos-like immunoreactivity induced by burst stimulation in the nucleus accumbens shell or in the lateral septum, although it blocked the stimulated enhancement of Fos-like immunoreactivity in the major island of Calleja. The present data indicate that, rather than the absolute mean discharge rate of midbrain dopamine neurons, the temporal organization of the action potentials they generate conveys information to their target areas.
本研究旨在通过电刺激大鼠内侧前脑束并随后借助Fos免疫组织化学法测定多巴胺靶区中作为神经元激活标志物的c-fos表达，来评估中脑多巴胺系统中不同突触前活动模式的突触后功能后果。在同一动物中使用体内伏安法监测内侧前脑束电刺激诱发的神经末梢多巴胺释放。对内侧前脑束施加由60串五个脉冲组成、持续1分钟的5Hz刺激。每3分钟重复此刺激15次。其模式由脉冲间隔定义，对于爆发式或规则间隔刺激，脉冲间隔分别为70毫秒或200毫秒。我们的结果表明，内侧前脑束的爆发式刺激增加了靶区多巴胺释放，同时增加了受刺激半球的基础Fos样免疫反应性，而规则刺激不影响该蛋白的表达。此外，爆发式刺激诱导的Fos样免疫反应性增加仅限于与边缘系统相关的结构，即伏隔核壳、外侧隔的中间部分和主要的Calleja岛，但在与运动相关的结构（伏隔核核心和纹状体）中未观察到。用D1多巴胺受体拮抗剂SCH23390（0.1mg/kg，腹腔注射）预处理可阻断内侧前脑束爆发式刺激诱导的Fos样免疫反应性增加，表明这些受体在观察到的效应中起作用。用5-羟色胺2A/2C受体拮抗剂利坦色林（0.4mg/kg，腹腔注射）预处理不影响伏隔核壳或外侧隔中爆发式刺激诱导的Fos样免疫反应性增加，尽管它阻断了Calleja岛中刺激增强的Fos样免疫反应性。目前的数据表明，中脑多巴胺神经元产生的动作电位的时间组织而非其绝对平均放电率向其靶区传递信息。
