Serotonin Differentially Regulates L5 Pyramidal Cell Classes of the Medial Prefrontal Cortex in Rats and Mice.

Serotonin Differentially Regulates L5 Pyramidal Cell Classes of the Medial Prefrontal Cortex in Rats and Mice.
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DOI:
10.1523/eneuro.0305-17.2018
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发表时间:
2018-01
期刊:
影响因子:
3.4
通讯作者:
Andrade R
Andrade R
中科院分区:
医学3区
文献类型:
--
作者:
Elliott MC;Tanaka PM;Schwark RW;Andrade R

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前额叶皮质接受密集的5-羟色胺能神经支配,在其调节中发挥重要作用。然而,5-羟色胺如何调节该区域不同类型的锥体细胞和中间神经元细胞尚不完全清楚。以前在大鼠身上的研究表明,5-羟色胺对第5层的两类锥体细胞有不同的调节作用。它通过激活5-HT2A受体来兴奋一类细胞,而通过共同激活5-HT1A和5-HT2A受体来更微妙地调节另一类细胞的整合特性。在这里,我们使用电生理记录,结合逆行标记和形态重建,显示第一类细胞对应于远程皮质分离神经元,第二类对应于脑内神经元。这些结果表明,在大鼠中,5-羟色胺促进皮质下的输出,同时更微妙地调节皮质和纹状体的输出。有趣的是,在大鼠身上获得的这些结果与之前报道的小鼠前额叶皮质的结果不同。因此,我们重新研究了5-羟色胺对小鼠的影响,并证实5-羟色胺主要激活长程皮质细胞上的抑制性5-HT1a受体。因此,5-羟色胺对大鼠和小鼠的这些细胞起相反的作用。最后,我们确定了小鼠的皮质5-羟色胺反应性在发育过程中是否受到调节。在出生后早期,5-羟色胺主要引起去极化的内向电流反应,而抑制性的5-HT1A受体介导的反应直到出生后第二周才变得明显。这些结果揭示了大鼠和小鼠在5-羟色胺能调节方面的共性和意想不到的差异。
The prefrontal cortex receives a dense serotonergic innervation that plays an important role in its regulation. However, how serotonin regulates different pyramidal and interneuron cell classes in this area is incompletely understood. Previous work in rats has shown that serotonin differentially regulates two classes of pyramidal cells in layer 5. It excites one class by activating 5-HT2A receptors, whereas it more subtly modulates the integrative properties of the other by co-activating 5-HT1A and 5-HT2A receptors. Here we have used electrophysiological recordings, combined with retrograde labeling and morphological reconstruction, to show that the first cell class corresponds to long range corticofugal neurons and the second corresponds to intratelencephalic neurons. These results suggest that, in rats, serotonin facilitates subcortical output while more subtly modulating cortico-cortical and cortico-striatal output. Interestingly, these results obtained in rats differ from those previously reported for mouse prefrontal cortex. Therefore we reinvestigated the effects of serotonin in mice and confirmed that serotonin predominantly activates inhibitory 5-HT1A receptors on long-range corticofugal cells. Thus serotonin exerts opposite effects on these cells in rats and mice. Finally, we determined whether cortical serotonin responsiveness in mice is regulated during development. Serotonin elicited predominantly depolarizing inward current responses during the early postnatal period, whereas inhibitory 5-HT1A receptor-mediated responses did not become evident until the end of the second postnatal week. These results reveal commonalities as well as unexpected differences in the serotonergic regulation of long-range corticofugal and intratelencephalic neurons of layer 5 in rat and mouse.