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首页> 外文期刊>Journal of Neurophysiology >The serotonin reuptake blocker citalopram destabilizes fictive locomotor activity in salamander axial circuits through 5-HT1A receptors
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The serotonin reuptake blocker citalopram destabilizes fictive locomotor activity in salamander axial circuits through 5-HT1A receptors

机译：Serotonin Reuptake障碍物CitalOltram通过5-HT1A受体破坏了蝾螈轴向电路中的虚构运动活性

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摘要

Serotoninergic (5-HT) neurons are powerful modulators of spinal locomotor circuits. Most studies on 5-HT modulation focused on the effect of exogenous 5-HT and these studies provided key information about the cellular mechanisms involved. Less is known about the effects of increased release of endogenous 5-HT with selective serotonin reuptake inhibitors. In mammals, such molecules were shown to destabilize the fictive locomotor output of spinal limb networks through 5-HT, A receptors. However, in tetrapods little is known about the effects of increased 5-HT release on the locomotor output of axial networks, which are coordinated with limb circuits during locomotion from basal vertebrates to mammals. Here, we examined the effect of citalopram on fictive locomotion generated in axial segments of isolated spinal cords in salamanders. a tetrapod where raphe 5-HT reticulospinal neurons and intraspinal 5-HT neurons are present as in other vertebrates. Using electrophysiological recordings of ventral roots, we show that fictive locomotion generated by bath-applied glutamatergic agonists is destabilized by citalopram. Citalopram-induced destabilization was prevented by a 5-HT1A receptor antagonist, whereas a 5-HT1A receptor agonist destabilized fictive locomotion. Using immunofluorescence experiments, we found 5-HT-positive fibers and varicosities in proximity with motoneurons and glutamatergic interneurons that are likely involved in rhythmogenesis. Our results show that increasing 5-HT release has a deleterious effect on axial locomotor activity through 5-HT1A receptors. This is consistent with studies in limb networks of turtle and mouse, suggesting that this part of the complex 5-HT modulation of spinal locomotor circuits is common to limb and axial networks in limbed vertebrates.
机译：血清奈宁能（5-HT）神经元是脊柱运动电路的强大调节剂。大多数关于5-HT调制的研究重点是外源5-HT的效果，这些研究提供了有关所涉及的蜂窝机制的关键信息。较少是关于增加内源性5-HT与选择性血清素再摄取抑制剂的影响的效果。在哺乳动物中，示出了这种分子使脊柱肢网络的虚拟运动输出稳定通过5-HT，受体。然而，在Tetrapods中，关于轴向网络的运动量输出上增加的5-HT释放的影响几乎是已知的，这在从基底脊椎动物到哺乳动物时与肢体电路协调。在这里，我们研究了西普拉姆在蝾螈孤立的脊髓轴段中产生的虚拟运动的影响。在其他脊椎动物中存在raphe 5-ht网状神经元和脊柱痉挛的5-Ht神经元的四射点。使用腹侧根的电生理记录，我们表明由浴应用的谷氨酸谷氨酸激动剂产生的虚构运动是由西普拉姆的破坏性。通过5-HT1A受体拮抗剂预防了西普拉克诱导的破坏化，而5-HT1A受体激动剂稳定的虚构运动。使用免疫荧光实验，我们发现5-HT阳性纤维和邻近的含有可能参与节律发生的运动神经元和谷氨酸谷氨酸间核心。我们的研究结果表明，通过5-HT1A受体对轴向运动活性产生有害影响。这与乌龟和小鼠的肢体网络中的研究一致，这表明脊柱运动电路的复杂5-HT调制的这一部分是肢体和血管脊椎动物中的轴向网络。

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