Mercuri N B, Grillner P, Bernardi G
Clinica Neurologica Dip. Sanita' Pubblica, Universita' di Roma Tor Vergata, Italy.
Neuroscience. 1996 Oct;74(3):785-92. doi: 10.1016/0306-4522(96)00189-3.
Repetitive local application of a short train of stimuli to the rat substantia nigra and ventral tegmental area elicited a predominant depolarizing, slow, long-lasting synaptic response in the dopaminergic cells intracellularly recorded in vitro. This slow excitatory postsynaptic potential ranged between 13 and 27 mV at holding potentials of about-75 mV and lasted for 0.2-6 s. It was not greatly affected by the perfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (10-20 microM), while it was potentiated in the presence of bicuculline methiodide (30 microM) or picrotoxin (50-100 microM) and 2-hydroxysaclofen (100-300 microM). In contrast, a substantial component of the slow excitatory postsynaptic potential was reversibly depressed, in a concentration-dependent manner, by the application of the N-methyl-D-aspartate receptor antagonists D,1-2-amino-5-phosphonovalerate (10-100 microM). Furthermore, the slow excitatory postsynaptic potential was reversibly increased by the superfusion of nominally magnesium-free solution. It was graded, increasing in amplitude with increased stimulus intensity, and was blocked by tetrodotoxin (0.5 microM). We suggest that a sustained activation of synaptic terminals containing excitatory amino acids mediates a slow excitatory postsynaptic potential in the dopaminergic cells of the midbrain. N-Methyl-D-aspartate receptors participate in the generation of this slow potential, while the alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate/kainate receptors do not seem to contribute substantially to this potential. This N-methyl-D-aspartate-mediated synaptic event could be implicated in the release of dopamine as well as in the excitotoxic injury of the dopaminergic neurons.
对大鼠黑质和腹侧被盖区进行短串刺激的重复局部应用，在体外细胞内记录的多巴胺能细胞中引发了主要的去极化、缓慢、持久的突触反应。这种缓慢的兴奋性突触后电位在约-75 mV的钳制电位下幅度在13至27 mV之间，持续0.2至6秒。它不受6-氰基-7-硝基喹喔啉-2,3-二酮（10-20 microM）灌注的显著影响，而在甲硫酸荷包牡丹碱（30 microM）或印防己毒素（50-100 microM）以及2-羟基舒氯芬（100-300 microM）存在时会增强。相反，通过应用N-甲基-D-天冬氨酸受体拮抗剂D-(-)-2-氨基-5-膦酰基戊酸（10-100 microM），缓慢兴奋性突触后电位的一个主要成分以浓度依赖性方式可逆性降低。此外，通过灌注名义上无镁的溶液，缓慢兴奋性突触后电位可逆性增加。它是分级的，幅度随刺激强度增加而增加，并被河豚毒素（0.5 microM）阻断。我们认为，含有兴奋性氨基酸的突触终末的持续激活介导了中脑多巴胺能细胞中的缓慢兴奋性突触后电位。N-甲基-D-天冬氨酸受体参与了这种缓慢电位的产生，而α-氨基-3-羟基-5-甲基异恶唑-4-丙酸/海人藻酸受体似乎对该电位没有实质性贡献。这种由N-甲基-D-天冬氨酸介导的突触事件可能与多巴胺的释放以及多巴胺能神经元的兴奋性毒性损伤有关。
