Dopamine increases excitability of pyramidal neurons in primate prefrontal cortex
Dopamine increases excitability of pyramidal neurons in primate prefrontal cortex
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DOI：
10.1152/jn.2000.84.6.2799
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发表时间：
2000-12-01
影响因子：
2.5
通讯作者：
Barrionuevo, G
中科院分区：
文献类型：
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作者：
Henze, DA;González-Burgos, GR;Barrionuevo, G
在人类和非人灵长类动物的工作记忆任务中，背外侧前额叶皮层（PFC）神经元网络的多巴胺能调节被认为在信息处理中起着重要作用。为了了解多巴胺（DA）这些作用的基本细胞机制，我们研究了DA对猕猴PFC 46区第3层锥体细胞细胞特性的影响。在PFC脑切片制备中，用尖形和全细胞膜片钳电极记录细胞内电压。所有记录的神经元在第3层（n = 86）表现出规则的尖峰放电特性与锥体神经元的一致。我们发现DA对这些细胞的静息膜电位和输入电阻没有明显的影响。然而，DA，在低至0.5 μ M的浓度，增加PFC细胞的兴奋性，响应于去极化电流步骤注射在索马。兴奋性增强与动作电位阈值的超极化偏移和第一峰间期缩短相关。这些效应需要激活D1样受体而不是D2样受体，因为它们被D1受体拮抗剂SCH 23390（3 μ M）抑制，但不被D2拮抗剂舒必利（2.5 μ M）显著改变。这些结果表明，第一次，DA调制的第3层锥体神经元在46区的猴背外侧PFC在体外的活动。此外，这些结果表明，通过这些影响单独，DA调制一般会增强PFC锥体神经元的兴奋性电流，达到动作电位起始位点的反应。
Dopaminergic modulation of neuronal networks in the dorsolateral prefrontal cortex (PFC) is believed to play an important role in information processing during working memory tasks in both humans and nonhuman primates. To understand the basic cellular mechanisms that underlie these actions of dopamine (DA), we have investigated the influence of DA on the cellular properties of layer 3 pyramidal cells in area 46 of the macaque monkey PFC. Intracellular voltage recordings were obtained with sharp and whole cell patch-clamp electrodes in a PFC brain-slice preparation. All of the recorded neurons in layer 3 (n = 86) exhibited regular spiking firing properties consistent with those of pyramidal neurons. We found that DA had no significant effects on resting membrane potential or input resistance of these cells. However DA, at concentrations as low as 0.5 muM, increased the excitability of PFC cells in response to depolarizing current steps injected at the soma. Enhanced excitability was associated with a hyperpolarizing shift in action potential threshold and a decreased first interspike interval. These effects required activation of D1-like but not D2-like receptors since they were inhibited by the D1 receptor antagonist SCH23390 (3 muM) but not significantly altered by the D2 antagonist sulpiride (2.5 muM). These results show, for the first time, that DA modulates the activity of layer 3 pyramidal neurons in area 46 of monkey dorsolateral PFC in vitro. Furthermore the results suggest that, by means of these effects alone, DA modulation would generally enhance the response of PFC pyramidal neurons to excitatory currents that reach the action potential initiation site.