Jovanović K, Petrov T, Greer J J, Stein R B
Department of Physiology, University of Alberta, Edmonton, Canada.
Exp Brain Res. 1996 Sep;111(1):57-67. doi: 10.1007/BF00229556.
The aims of the present study were to: (1) study the role of serotonin (5-HT) in modulating the central pattern generator (CPG) underlying locomotion in the mudpuppy (Necturus maculatus); (2) investigate whether there is an intrinsic spinal serotonergic system. These aims were achieved by the use of pharmacological and immunocytochemical methods. To study modulation of the locomotor pattern and rhythm, we applied 5-HT, its uptake blocker zimelidine, and a variety of 5-HT receptor agonists and antagonists to an in vitro brainstem-spinal cord preparation isolated from the mudpuppy. The preparation consisted of the first five segments of the spinal cord and the right forelimb attached by the brachial plexus. The spinal CPG for locomotion was activated chemically by adding NMDA to the superfusing solution. During locomotion, bipolar electromyographic (EMG) recordings were made unilaterally from flexor and extensor ulnae muscles. 5-HT on its own did not induce locomotion, but it did have a profound modulatory effect on NMDA-induced locomotion. 5-HT produced a dose-dependent increase in the overall cycle duration and enhanced the EMG burst duration. Use of zimelidine indicated that there is an endogenous release of 5-HT which modulated the locomotor rhythm. The endogenous release was antagonized by 5-HT1/5-HT2 receptor antagonist methiothepin. Immunocytochemical analysis, in which the entire spinal cord of the mudpuppy was used, revealed that there were more than one type of spinal serotonergic neuron. They were differentiated according to the cell diameter, shape, and arborization pattern of their processes. These neurons were located within the central gray matter ventrolateral to the central canal. Our results suggest that 5-HT plays an important role in modulating the locomotor CPG in the mudpuppy, by acting through a well-developed spinal serotonergic system. This is in contrast to what has been reported in higher vertebrates, where serotonergic innervation is derived from supraspinal structures.
（1）研究血清素（5-羟色胺，5-HT）在调节泥螈（斑泥螈，Necturus maculatus）运动的中枢模式发生器（CPG）中的作用；（2）研究是否存在内在的脊髓5-羟色胺能系统。这些目的通过药理学和免疫细胞化学方法得以实现。为了研究运动模式和节律的调节，我们将5-HT、其摄取阻断剂齐美利定以及多种5-HT受体激动剂和拮抗剂应用于从泥螈分离的体外脑干-脊髓标本。该标本由脊髓的前五个节段和通过臂丛神经连接的右前肢组成。通过向灌注液中添加N-甲基-D-天冬氨酸（NMDA）来化学激活用于运动的脊髓CPG。在运动过程中，从尺侧屈肌和伸肌单侧进行双极肌电图（EMG）记录。5-HT自身不会诱发运动，但它对NMDA诱发的运动具有显著的调节作用。5-HT使整个周期时长呈剂量依赖性增加，并延长了EMG爆发持续时间。使用齐美利定表明存在5-HT的内源性释放，它调节了运动节律。5-HT1/5-HT2受体拮抗剂甲硫噻平可拮抗这种内源性释放。使用泥螈的整个脊髓进行免疫细胞化学分析显示，存在不止一种类型的脊髓5-羟色胺能神经元。它们根据细胞直径、形状及其突起的分支模式进行区分。这些神经元位于中央管腹外侧的中央灰质内。我们的结果表明，5-HT通过发育良好的脊髓5-羟色胺能系统发挥作用，在调节泥螈的运动CPG中起重要作用。这与在高等脊椎动物中所报道的情况形成对比，在高等脊椎动物中，5-羟色胺能神经支配源自脊髓上结构。
