Otani S, Blond O, Desce J M, Crépel F
Laboratoire de Neurobiologie et Neuropharmacologie du Développement, Institut des Neurosciences, CNRS Université de Paris VI, Pierre et Marie Curie, France.
Neuroscience. 1998 Aug;85(3):669-76. doi: 10.1016/s0306-4522(97)00677-5.
Using sharp-electrode intracellular recordings, we studied the dopaminergic facilitation of synaptic plasticity in layer I-II afferents--layer V neuron glutamatergic synapses in rat prefrontal cortex in vitro. Tetanic stimulation (100 pulses at 50 Hz, four times at 0.1 Hz) to layer I-II afferents induced N-methyl-D-aspartate receptor-independent long-term depression (>40 min) of the glutamatergic synapses when the stimulation was coupled with a bath-application of dopamine. Tetanic stimulation alone did not induce lasting synaptic changes. Dopamine application alone transiently depressed synaptic responses, which fully recovered within 30 min. Pharmacological analyses with antagonists suggested that dopamine action on either D1-like or D2-like receptors can facilitate the induction of long-term depression. However, results with agonists were not fully consistent with the antagonist results: while a D2 agonist mimicked the facilitatory dopamine effect, D1 agonists failed to mimic the effect. We also analysed the synaptic responses during tetanus and found that dopamine prolongs membrane depolarization during high-frequency inputs. Postsynaptic membrane depolarization is indeed critical for long-term depression induction in the presence of dopamine, since postsynaptic hyperpolarization during tetanus blocked the dopaminergic facilitation of long-term depression induction. Postsynaptic injection of the Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetra-acetic acid (100 mM in the electrode) also blocked long-term depression induction. Our results show that dopamine lowers the threshold for long-term depression induction in rat prefrontal glutamatergic transmission. A possible underlying mechanism of this dopaminergic facilitation is the enhancement of postsynaptic depolarization during tetanus by dopamine, which may increase the amount of Ca2+ entry from voltage-gated channels to the level sufficient for plasticity induction.
我们采用尖锐电极细胞内记录技术，在体外研究了大鼠前额叶皮层I-II层传入纤维与V层神经元之间谷氨酸能突触的多巴胺能介导的突触可塑性。当对I-II层传入纤维施加强直刺激（50 Hz，100个脉冲，0.1 Hz重复4次）并同时浴灌多巴胺时，可诱导谷氨酸能突触产生不依赖N-甲基-D-天冬氨酸受体的长时程抑制（>40分钟）。单独的强直刺激不会诱导持久的突触变化。单独应用多巴胺会短暂抑制突触反应，但在30分钟内可完全恢复。使用拮抗剂的药理学分析表明，多巴胺作用于D1样或D2样受体均可促进长时程抑制的诱导。然而，激动剂的实验结果与拮抗剂的结果并不完全一致：虽然D2激动剂可模拟多巴胺的促进作用，但D1激动剂未能模拟该效应。我们还分析了强直刺激期间的突触反应，发现多巴胺可延长高频输入时的膜去极化。突触后膜去极化在多巴胺存在的情况下对长时程抑制的诱导确实至关重要，因为强直刺激期间的突触后超极化会阻断多巴胺对长时程抑制诱导的促进作用。突触后注射Ca2+螯合剂双（邻氨基苯氧基）-N,N,N',N'-四乙酸（电极内浓度为100 mM）也会阻断长时程抑制的诱导。我们的结果表明，多巴胺可降低大鼠前额叶谷氨酸能传递中长时程抑制诱导的阈值。这种多巴胺能促进作用的一个潜在机制可能是多巴胺增强了强直刺激期间的突触后去极化，这可能会增加从电压门控通道进入的Ca2+量，使其达到足以诱导可塑性的水平。
