Grenhoff J, Ugedo L, Svensson T H
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Acta Physiol Scand. 1988 Sep;134(1):127-32. doi: 10.1111/j.1748-1716.1988.tb08468.x.
Dopamine neurons of the substantia nigra (A9) and the ventral tegmental area (A10), giving rise to the nigrostriatal and mesolimbic dopamine pathways, respectively, are commonly supposed to show similar electrophysiological activity. There are, however, instances where the two systems are differently modulated. To assess possible physiological differences in the neuronal activity of A9 and A10 neurons, randomly sampled single cells were extracellularly recorded in the chloral hydrate-anaesthetized male rat. In addition to firing rate, the degree of burst firing and the regularity of firing were quantitatively analysed. Our results show that although A9 and A10 do not differ in firing rates, A10 neuronal activity is markedly less regular and shows a higher degree of burst firing, as judged from analysis of inter-spike time interval histograms. Mean burst firing values were 3% for the A9, and 23% for the A10 neurons. Regularity was described by variation coefficients of inter-spike time interval histograms. The mean variation coefficient was 38.4% in the A9 group and 63.8% in the A10 group, i.e. the A10 neuronal firing was less regular. The difference in regularity is partly, but not fully, dependent on the difference in burst firing. Previous biochemical and physiological studies strongly support the functional significance of modulatory changes in midbrain dopamine-cell firing patterns. Since the firing pattern of midbrain dopamine cells seems to be controlled by synaptic inputs, our results indicate a higher tonic modulatory influence on the A10 than on the A9 neurons. Thus the present results imply the pharmacological possibility of preferentially affecting A10 versus A9 dopamine cell function.
黑质(A9)和腹侧被盖区(A10)的多巴胺能神经元分别形成黑质纹状体和中脑边缘多巴胺能通路,通常认为它们表现出相似的电生理活动。然而,也存在这两个系统受到不同调节的情况。为了评估A9和A10神经元神经活动可能存在的生理差异,在水合氯醛麻醉的雄性大鼠中对随机采样的单个细胞进行细胞外记录。除了放电频率外,还对爆发式放电程度和放电规律性进行了定量分析。我们的结果表明,虽然A9和A10在放电频率上没有差异,但从峰间时间间隔直方图分析判断,A10神经元活动的规律性明显较差,且爆发式放电程度更高。A9神经元的平均爆发式放电值为3%,A10神经元为23%。通过峰间时间间隔直方图的变异系数来描述规律性。A9组的平均变异系数为38.4%,A10组为63.8%,即A10神经元放电的规律性较差。规律性的差异部分但并非完全取决于爆发式放电的差异。先前的生化和生理研究有力地支持了中脑多巴胺能细胞放电模式调节变化的功能意义。由于中脑多巴胺能细胞的放电模式似乎受突触输入控制,我们的结果表明对A10神经元的紧张性调节影响高于A9神经元。因此,目前的结果意味着在药理学上有可能优先影响A10而非A9多巴胺能细胞的功能。