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首页> 外文期刊>The European Journal of Neuroscience >Contribution of 5-HT to locomotion - the paradox of Pet-1(-/-) mice.
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Contribution of 5-HT to locomotion - the paradox of Pet-1(-/-) mice.

机译：5-HT对运动的贡献-Pet-1（-/-）小鼠的悖论。

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摘要

Serotonin (5-HT) plays a critical role in locomotor pattern generation by modulating the rhythm and the coordinations. Pet-1, a transcription factor selectively expressed in the raphe nuclei, controls the differentiation of 5-HT neurons. Surprisingly, inactivation of Pet-1 (Pet-1(-/-) mice) that causes a 70% reduction in the number of 5-HT-positive neurons in the raphe does not impair locomotion in adult mice. The goal of the present study was to investigate the operation of the locomotor central pattern generator (CPG) in neonatal Pet-1(-/-) mice. We first confirmed, by means of immunohistochemistry, that there is a marked reduction of 5-HT innervation in the lumbar spinal cord of Pet-1(-/-) mice. Fictive locomotion was induced in the in vitro neonatal mouse spinal cord preparation by bath application of N-methyl-d,l-Aspartate (NMA) alone or together with dopamine and 5-HT. A locomotor pattern characterized by left-right and flexor-extensor alternations was observed in both conditions. Increasing the concentration of 5-HT from 0.5 to 5 mum impaired the pattern in Pet-1(-/-) mice. We tested the role of endogenous 5-HT in the NMA-induced fictive locomotion. Application of 5-HT(2) or 5-HT(7) receptor antagonists affected the NMA-induced fictive locomotion in both heterozygous and homozygous mice although the effects were weaker in the latter strain. This may be, at least partly, explained by the reduced expression of 5-HT(2A) R as observed by means of immunohistochemistry. These results suggest that compensatory mechanisms take place in Pet-1(-/-) mice that make locomotion less dependent upon 5-HT.
机译：5-羟色胺（5-HT）通过调节节奏和协调性在运动模式产生中起关键作用。 Pet-1是一种在缝核中选择性表达的转录因子，它控制5-HT神经元的分化。出人意料的是，Pet-1（Pet-1（-/-）小鼠）的失活导致缝隙中5-HT阳性神经元数量减少70％不会损害成年小鼠的运动。本研究的目的是研究新生的Pet-1（-/-）小鼠的运动中心模式发生器（CPG）的操作。我们首先通过免疫组织化学证实，Pet-1（-/-）小鼠的腰脊髓5-HT神经支配明显减少。通过单独应用N-甲基-d，l-天冬氨酸（NMA）或与多巴胺和5-HT一起应用浴，在体外新生小鼠脊髓制备中诱导了虚构的运动。在两种情况下均观察到以左右交替和屈伸交替为特征的运动模式。 5-HT的浓度从0.5增至5毫米会损害Pet-1（-/-）小鼠的模式。我们测试了内源性5-HT在NMA诱导的虚构运动中的作用。 5-HT（2）或5-HT（7）受体拮抗剂的应用影响NMA诱导的杂合小鼠和纯合小鼠的虚构运动，尽管后者的作用较弱。至少部分地可以通过免疫组织化学观察到5-HT（2A）R表达降低来解释。这些结果表明补偿机制发生在Pet-1（-/-）小鼠中，使运动对5-HT的依赖性降低。

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