Mereu G, Lilliu V, Casula A, Vargiu P F, Diana M, Musa A, Gessa G L
Department of Experimental Biology, B. Loddo, University of Cagliari, Italy.
Neuroscience. 1997 Apr;77(4):1029-36. doi: 10.1016/s0306-4522(96)00474-5.
Dopamine neurons in midbrain coronal slices from adult rats (40-70 days old) discharged only in pacemaker-like mode. Irregular or bursting mode was never observed. In contrast, dopamine neurons in slices from immature rats (15-21 days old) exhibited not only pacemaker-like firing (53.4% of neurons), but also irregular and bursting patterns (28.3 and 18.3%, respectively). Glutamate and kainate increased the firing rate but failed to induce bursts in dopamine neurons from either adult or immature rats. N-Methyl-D-aspartate augmented the firing rate in all neurons from adult rats and produced a modest increase of bursts in only three out of 18 cells. In slices from immature rats, N-methyl-D-aspartate activated the discharge rate in all neurons and also induced bursts in 37 and 53% of pacemaker and irregular neurons, respectively, and increased the occurrence of spikes in bursts in 76% of spontaneously bursting neurons. The selective N-methyl-D-aspartate receptor antagonist (+/-)2-amino,5-phosphonopentanoic acid prevented N-methyl-D-aspartate-induced changes and also reduced spontaneous bursts, suggesting that bursting discharge is mediated by N-methyl-D-aspartate receptor activation. While pacemaker neurons from immature and from adult rats exhibited the same sensitivity to N-methyl-D-aspartate-induced stimulation of firing rate, spontaneously bursting neurons were more sensitive than pacemaker neurons from either immature or adult rats. The present study indicates that spontaneous bursting, dependent on N-methyl-D-aspartate receptor activation, is present, and may be induced, in dopamine neurons in slices from immature rats. Its absence from cells in slices from adult rats may reflect a reduced sensitivity of N-methyl-D-aspartate receptors on dopamine or the loss of the N-methyl-D-aspartate-activated burst generator.
成年大鼠（40 - 70日龄）中脑冠状切片中的多巴胺能神经元仅以类似起搏器的模式放电。从未观察到不规则或爆发性模式。相比之下，未成熟大鼠（15 - 21日龄）切片中的多巴胺能神经元不仅表现出类似起搏器的放电（53.4%的神经元），还表现出不规则和爆发性模式（分别为28.3%和18.3%）。谷氨酸和 kainate 增加了放电频率，但未能在成年或未成熟大鼠的多巴胺能神经元中诱导出爆发。N - 甲基 - D - 天冬氨酸增加了成年大鼠所有神经元的放电频率，并且仅在18个细胞中的3个细胞中产生了适度的爆发增加。在未成熟大鼠的切片中，N - 甲基 - D - 天冬氨酸激活了所有神经元的放电频率，并且分别在37%的起搏器神经元和53%的不规则神经元中诱导出爆发，并且在76%的自发爆发神经元中增加了爆发中的尖峰出现率。选择性N - 甲基 - D - 天冬氨酸受体拮抗剂（±）2 - 氨基 - 5 - 膦酰基戊酸阻止了N - 甲基 - D - 天冬氨酸诱导的变化，并且还减少了自发爆发，表明爆发性放电是由N - 甲基 - D - 天冬氨酸受体激活介导的。虽然未成熟和成年大鼠的起搏器神经元对N - 甲基 - D - 天冬氨酸诱导的放电频率刺激表现出相同的敏感性，但自发爆发神经元比未成熟或成年大鼠的起搏器神经元更敏感。本研究表明，依赖于N - 甲基 - D - 天冬氨酸受体激活的自发爆发在未成熟大鼠切片中的多巴胺能神经元中存在，并且可能被诱导。成年大鼠切片中的细胞缺乏这种现象可能反映了多巴胺上N - 甲基 - D - 天冬氨酸受体敏感性的降低或N - 甲基 - D - 天冬氨酸激活的爆发发生器的丧失。
