Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, China.
PLoS One. 2013 Aug 20;8(8):e71880. doi: 10.1371/journal.pone.0071880. eCollection 2013.
Dopamine (DA) receptors in the prefrontal cortex (PFC) modulate both synaptic and intrinsic plasticity that may contribute to cognitive processing. However, the ionic basis underlying DA actions to enhance neuronal plasticity in PFC remains ill-defined. Using whole-cell patch-clamp recordings in layer V-VI pyramidal cells in prepubertal rat PFC, we showed that DA, via activation of D1/5, but not D2/3/4, receptors suppress a Ca(2+)-dependent, apamin-sensitive K(+) channel that mediates post-spike/burst afterhyperpolarization (AHP) to enhance neuronal excitability of PFC neurons. This inhibition is not dependent on HCN channels. The D1/5 receptor activation also enhanced an afterdepolarizing potential (ADP) that follows the AHP. Additional single-spike analyses revealed that DA or D1/5 receptor activation suppressed the apamin-sensitive post-spike mAHP, further contributing to the increase in evoked spike firing to enhance the neuronal excitability. Taken together, the D1/5 receptor modulates intrinsic mechanisms that amplify a long depolarizing input to sustain spike firing outputs in pyramidal PFC neurons.
前额叶皮层（PFC）中的多巴胺（DA）受体调节突触和内在可塑性，这可能有助于认知加工。然而，增强 PFC 中神经元可塑性的 DA 作用的离子基础仍未明确。我们在青春期前大鼠 PFC 的 V-VI 层锥体神经元中使用全细胞膜片钳记录，结果表明，DA 通过激活 D1/5 受体，但不激活 D2/3/4 受体，抑制钙依赖性、蜂毒明肽敏感的钾（K+）通道，该通道介导尖峰/爆发后超极化（AHP），从而增强 PFC 神经元的兴奋性。这种抑制不依赖于 HCN 通道。D1/5 受体的激活也增强了 AHP 之后的去极化后电位（ADP）。进一步的单尖峰分析显示，DA 或 D1/5 受体的激活抑制了蜂毒明肽敏感的尖峰后 mAHP，这进一步增加了诱发尖峰放电，从而增强了神经元的兴奋性。综上所述，D1/5 受体调节内在机制，放大长时去极化输入，以维持 PFC 锥体神经元的尖峰放电输出。
