Chergui K, Charléty P J, Akaoka H, Saunier C F, Brunet J L, Buda M, Svensson T H, Chouvet G
INSERM U 171 and CNRS URA 1195, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
Eur J Neurosci. 1993 Feb 1;5(2):137-44. doi: 10.1111/j.1460-9568.1993.tb00479.x.
Midbrain dopamine neurons in vivo discharge in a single-spike firing pattern or in a burst-firing pattern. Such activity in vivo strikingly contrasts with the pacemaker activity of the same dopamine neurons recorded in vitro. We have recently shown that burst activity in vivo of midbrain dopamine neurons is due to the local activation of excitatory amino acid receptors, as microapplication of the broad-spectrum antagonist of excitatory amino acids, kynurenic acid, strongly regularized the spontaneous firing pattern of these dopamine neurons. In the present study, we investigated which subtypes of excitatory amino acid receptors are involved in the burst-firing of midbrain dopamine neurons in chloral hydrate-anaesthetized rats, iontophoretic or pressure microejections of 6-cyano, 7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (NMDA) receptor antagonist, did not alter the spontaneous burst firing of dopamine neurons (n = 36). In contrast, similar ejections of (+-)2-amino,5-phosphonopentanoic acid (AP-5), a specific antagonist at NMDA receptors, markedly regularized the firing pattern by reducing the occurrence of bursts (n = 52). In addition, iontophoretic ejections of NMDA, but not kainate or quisqualate, elicited a discharge of these dopamine neurons in bursts (n = 20, 12 and 14, respectively). These data suggest that burst-firing of midbrain dopamine neurons in vivo results from the tonic activation of NMDA receptors by endogenous excitatory amino acids. In view of the critical dependency of catecholamine release on the discharge pattern of source neurons, excitatory amino acid inputs to midbrain dopamine neurons may constitute a major physiological substrate in the control of the dopamine level in target areas.
中脑多巴胺神经元在体内以单峰放电模式或爆发式放电模式进行放电。这种体内活动与在体外记录到的相同多巴胺神经元的起搏器活动形成了鲜明对比。我们最近发现，中脑多巴胺神经元在体内的爆发式活动是由于兴奋性氨基酸受体的局部激活，因为应用兴奋性氨基酸的广谱拮抗剂犬尿喹啉酸进行微量注射，能强烈地使这些多巴胺神经元的自发放电模式趋于规则。在本研究中，我们调查了在水合氯醛麻醉的大鼠中，哪些兴奋性氨基酸受体亚型参与了中脑多巴胺神经元的爆发式放电。离子电泳或压力微量注射非N-甲基-D-天冬氨酸（NMDA）受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX），并不会改变多巴胺神经元的自发放电爆发（n = 36）。相反，特异性NMDA受体拮抗剂（±）-2-氨基-5-膦酰基戊酸（AP-5）进行类似的微量注射，通过减少爆发的发生，显著地使放电模式趋于规则（n = 52）。此外，离子电泳微量注射NMDA，但不是注射海人藻酸或quisqualate，能引发这些多巴胺神经元的爆发式放电（分别为n = 20、12和14）。这些数据表明，中脑多巴胺神经元在体内的爆发式放电是内源性兴奋性氨基酸对NMDA受体进行持续性激活的结果。鉴于儿茶酚胺释放对源神经元放电模式的关键依赖性，中脑多巴胺神经元的兴奋性氨基酸输入可能构成了控制靶区域多巴胺水平的主要生理基础。
