Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America.
PLoS One. 2011 Feb 24;6(2):e16970. doi: 10.1371/journal.pone.0016970.
Serotonin exerts a powerful influence on neuronal excitability. In this study, we investigated the effects of serotonin on different neuronal populations in prefrontal cortex (PFC), a major area controlling emotion and cognition. Using whole-cell recordings in PFC slices, we found that bath application of 5-HT dose-dependently increased the firing of FS (fast spiking) interneurons, and decreased the firing of pyramidal neurons. The enhancing effect of 5-HT in FS interneurons was mediated by 5-HT₂ receptors, while the reducing effect of 5-HT in pyramidal neurons was mediated by 5-HT₁ receptors. Fluoxetine, the selective serotonin reuptake inhibitor, also induced a concentration-dependent increase in the excitability of FS interneurons, but had little effect on pyramidal neurons. In rats with chronic fluoxetine treatment, the excitability of FS interneurons was significantly increased, while pyramidal neurons remained unchanged. Fluoxetine injection largely occluded the enhancing effect of 5-HT in FS interneurons, but did not alter the reducing effect of 5-HT in pyramidal neurons. These data suggest that the excitability of PFC interneurons and pyramidal neurons is regulated by exogenous 5-HT in an opposing manner, and FS interneurons are the major target of Fluoxetine. It provides a framework for understanding the action of 5-HT and antidepressants in altering PFC network activity.
血清素对神经元兴奋性有很强的影响。在这项研究中，我们研究了血清素对前额叶皮层（PFC）中不同神经元群体的影响，前额叶皮层是控制情绪和认知的主要区域。我们通过在 PFC 切片上进行全细胞记录，发现 5-HT 的浴应用剂量依赖性地增加了 FS（快速尖峰）中间神经元的放电，而降低了锥体神经元的放电。5-HT 在 FS 中间神经元中的增强作用是由 5-HT₂ 受体介导的，而 5-HT 在锥体神经元中的降低作用是由 5-HT₁ 受体介导的。选择性血清素再摄取抑制剂氟西汀也诱导 FS 中间神经元兴奋性的浓度依赖性增加，但对锥体神经元几乎没有影响。在慢性氟西汀处理的大鼠中，FS 中间神经元的兴奋性显著增加，而锥体神经元保持不变。氟西汀注射大大阻断了 5-HT 在 FS 中间神经元中的增强作用，但不改变 5-HT 在锥体神经元中的降低作用。这些数据表明，外源性 5-HT 以相反的方式调节 PFC 中间神经元和锥体神经元的兴奋性，而 FS 中间神经元是氟西汀的主要靶标。它为理解 5-HT 和抗抑郁药在改变 PFC 网络活动中的作用提供了一个框架。
