Williams G V, Millar J
Department of Physiology, Queen Mary and Westfield College, London, U.K.
Neuroscience. 1990;39(1):1-16. doi: 10.1016/0306-4522(90)90217-r.
Voltammetric analysis was combined with single unit recording to measure the effects of endogenous dopamine, released by electrical stimulation of the median forebrain bundle, on neuronal activity in the rat striatum in vivo. Fast differential ramp voltammetry, a more sensitive form of fast cyclic voltammetry, was used to measure extracellular dopamine levels during a 50-ms scan epoch every 500 ms. Using the same carbon fibre microelectrode, neuronal activity was recorded in between the electrochemical epochs. A steady-state electrochemical signal equivalent to about 100 nM dopamine was seen in the unstimulated striatum. The responses of 122 striatal units to stimulated dopamine release were recorded in 37 acute experiments. Ninety-one units which displayed a large spike amplitude (greater than or equal to 50 microV) were recorded during stimulated release of dopamine initially to levels of between 100 and 500 nM. The majority (49) showed a profound excitation, 23 showed inhibition, and nine units gave complex responses. Only 10 units were unresponsive. All the responses of these large units outlasted the transient increase in dopamine levels, often for more than 1 min. In contrast, all the 31 units which displayed a small spike amplitude (less than 50 microV) were powerfully activated by dopamine release within this range. Administration of alpha-methyl-para-tyrosine (250 mg/kg i.p.) abolished both dopamine release and the response of the five large units and four small units examined, indicating that the neuronal response was directly attributable to dopamine. Dopamine release was increased by increasing the stimulus duration over the range 0.25-10 s. With increasing levels of dopamine release the excitatory response of large units rose to a maximum and then decreased until it was eventually transformed entirely into an inhibition at dopamine levels above 1 microM. In contrast, the excitatory response of small units always increased in magnitude with increasing dopamine release to levels greater than 1 microM. The large units that showed inhibition at low levels of dopamine were also inhibited at high levels. Tail-pinch stimuli excited 21/23 large units and all seven small units tested, although this stimulus did not evoke a detectable rise in dopamine levels. We suggest that the fundamental action of dopamine in the striatum is excitation, whether involving D1 or D2 receptors. The small units described here could be inhibitory interneurons which convert the excitatory response of large units into inhibition. Dopamine may regulate striatal function by enhancing particular input-output pathways while also activating lateral inhibitory mechanisms serving to "gate-out" alternative outputs.
伏安法分析与单神经元记录相结合，以测量通过电刺激中脑前脑束释放的内源性多巴胺对大鼠纹状体神经元活动的影响。快速差分斜坡伏安法是快速循环伏安法的一种更灵敏形式，用于每500毫秒的50毫秒扫描期内测量细胞外多巴胺水平。使用同一根碳纤维微电极，在电化学测量期之间记录神经元活动。在未受刺激的纹状体中可观察到相当于约100 nM多巴胺的稳态电化学信号。在37个急性实验中记录了122个纹状体神经元对刺激引起的多巴胺释放的反应。在多巴胺最初释放至100至500 nM水平的过程中，记录到91个具有大动作电位幅度（大于或等于50 μV）的神经元。其中大多数（49个）表现出强烈兴奋，23个表现出抑制，9个神经元给出复杂反应。只有10个神经元无反应。这些大神经元的所有反应都持续超过多巴胺水平的短暂升高，通常超过1分钟。相比之下，所有31个具有小动作电位幅度（小于50 μV）的神经元在此范围内均被多巴胺释放强烈激活。腹腔注射α-甲基-对-酪氨酸（250 mg/kg）消除了多巴胺释放以及所检测的5个大神经元和4个小神经元的反应，表明神经元反应直接归因于多巴胺。通过在0.25至10秒范围内增加刺激持续时间，多巴胺释放增加。随着多巴胺释放水平的增加，大神经元的兴奋反应先上升至最大值，然后下降，直到在多巴胺水平高于1 μM时最终完全转变为抑制。相比之下，小神经元的兴奋反应总是随着多巴胺释放增加至大于1 μM水平而在幅度上增加。在低多巴胺水平表现出抑制的大神经元在高多巴胺水平时也受到抑制。夹尾刺激使所测试的21/23个大神经元和所有7个小神经元兴奋，尽管该刺激未引起可检测到的多巴胺水平升高。我们认为多巴胺在纹状体中的基本作用是兴奋，无论涉及D1还是D2受体。这里描述的小神经元可能是抑制性中间神经元，它们将大神经元的兴奋反应转化为抑制。多巴胺可能通过增强特定的输入-输出通路来调节纹状体功能，同时还激活侧向抑制机制以“排除”其他输出。
