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通过体内电化学研究大鼠中脑多巴胺能神经元释放的多巴胺与脉冲流之间的非线性关系。

Nonlinear relationship between impulse flow and dopamine released by rat midbrain dopaminergic neurons as studied by in vivo electrochemistry.

作者信息

Gonon F G

机构信息

INSERM U 171, Hôpital Ste Eugénie, St Genis Laval, France.

出版信息

Neuroscience. 1988 Jan;24(1):19-28. doi: 10.1016/0306-4522(88)90307-7.

DOI:10.1016/0306-4522(88)90307-7
PMID:3368048
Abstract

Mesolimbic dopaminergic neurons discharge either in a single spike mode or in a bursting pattern. In order to investigate the influence of these patterns on dopamine release, extracellular dopamine was electrochemically monitored in vivo in the olfactory tuberculum of anaesthetized rats by means of two approaches. In the first, a pure signal, unequivocally corresponding to extracellular dopamine, was recorded every minute from pargyline treated rats by differential normal pulse voltammetry combined with electrochemically treated carbon fibre electrodes. In the second, the differential current solely due to oxidation of all the catechols was monitored every 1 s in drug-free rats by differential pulse amperometry. In basal conditions this current was mainly due to extracellular DOPAC. However, electrical stimulation of the dopaminergic pathway for 20 s elicited an immediate increase in this signal. This effect was due to evoked dopamine release since it was strongly enhanced by amphetamine (2 mg/kg) or pargyline (75 mg/kg) injections. As studied with both approaches, the evoked increase in extracellular dopamine concentration was immediate and lasted as long as the stimulation. The amplitude of the effect depended on the frequency of the stimulation (from 3 to 14 Hz) in an exponential manner but never exceeded 1 microM dopamine. Bursting stimulations (frequency within the trains: 14 Hz) were twice as potent as regularly spaced ones, having the same average frequency (5 Hz). In conditions which mimicked the spontaneous activity of dopaminergic neurons when they switch from one pattern to the other (4 Hz regularly spaced stimulation versus trains at a mean frequency of 6 Hz), the bursting stimulations were found to be up to 6 times more potent. Therefore, as regards the functional efficacy of DA neurons, bursting might be much more important than mean firing frequency.

摘要

中脑边缘多巴胺能神经元以单峰模式或爆发模式放电。为了研究这些模式对多巴胺释放的影响,通过两种方法在体内对麻醉大鼠的嗅结节进行细胞外多巴胺的电化学监测。第一种方法,使用经电化学处理的碳纤维电极,通过差分正常脉冲伏安法每分钟从帕吉林处理的大鼠中记录一个明确对应于细胞外多巴胺的纯信号。第二种方法,在未用药的大鼠中,通过差分脉冲安培法每秒监测一次仅由所有儿茶酚氧化产生的差分电流。在基础条件下,该电流主要归因于细胞外二羟基苯乙酸(DOPAC)。然而,对多巴胺能通路进行20秒的电刺激会立即引起该信号增加。这种效应是由于诱发的多巴胺释放,因为苯丙胺(2毫克/千克)或帕吉林(75毫克/千克)注射会强烈增强这种效应。使用这两种方法研究发现,诱发的细胞外多巴胺浓度增加是即时的,并且只要刺激持续就会持续。效应的幅度以指数方式取决于刺激频率(3至14赫兹),但多巴胺浓度从未超过1微摩尔。爆发性刺激(串内频率:14赫兹)的效力是平均频率相同(5赫兹)的等间隔刺激的两倍。在模拟多巴胺能神经元从一种模式转换到另一种模式时的自发活动的条件下(4赫兹等间隔刺激与平均频率为6赫兹的串刺激),发现爆发性刺激的效力高达6倍。因此,就多巴胺能神经元的功能效力而言,爆发可能比平均放电频率重要得多。

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