Mesce K A, Crisp K M, Gilchrist L S
Graduate Program in Neuroscience, University of Minnesota, St. Paul, Minnesota 55108, USA.
J Neurophysiol. 2001 May;85(5):2039-46. doi: 10.1152/jn.2001.85.5.2039.
It is well established that neural networks respond to a wide variety of modulatory substances by which they can become reconfigured, yet few studies have examined the effects of neurotransmitter mixtures on such networks. In a previous study of the medicinal leech using triple intracellular recordings, we found that stimulation of identified mechanosensory neurons activated both the serotonergic cell 21 (a swimgating neuron) and the dorsal lateral octopamine (DLO) cell. Because these findings suggested that serotonin (5-HT) and octopamine (OA) may be released together, we investigated the effects of 5-HT and OA mixtures on isolated nerve cords of Hirudo medicinalis (which contained both head and tail brains). Fifty micromolar OA, 50 microM 5-HT, or a mixture of 50 microM OA and 50 microM 5-HT was bath applied to the nerve cord under constant perfusion conditions. Additional experiments were performed with combinations of either 25 or 100 microM OA and 5-HT. Neural activity was examined specifically in the segmentally repeated dorsal posterior (DP) nerve because it has been shown to contain identified swim motor units. Nonadditive effects of amine combinations were most apparent in their ability to decrease overall activity in the DP nerve and to alter patterned motor activity in the form of fictive swimming. Whereas swim burst activity has been previously shown to increase in nerve cords bathed in either 5-HT or OA solutions alone, we demonstrated that a mixture of the two amines resulted in a robust decrease in the number of swim bursts expressed and an inhibition of swim activity in preparations already swimming. Most compelling was the observation that when the amine mixture was replaced with normal saline, swim burst activity increased dramatically. We discuss that the effects of amine mixtures may be due to their interaction with descending interneurons known to trigger and inhibit swimming as the mixture-induced effects were not observed in nerve cords lacking the head and tail brains. Because the net effect of the two amines was not simply additive (i.e., 5-HT or OA is known to activate swimming, yet the mix inhibits swimming), this result reveals yet another layer of complexity inherent in "simpler" invertebrate nervous systems.
神经网络对多种调节物质产生反应，通过这些调节物质它们能够重新配置，这一点已经得到充分证实，然而很少有研究考察神经递质混合物对这类网络的影响。在先前一项使用三重细胞内记录对药用水蛭进行的研究中，我们发现刺激已鉴定的机械感觉神经元会激活血清素能细胞21（一种摆动门控神经元）和背外侧章鱼胺（DLO）细胞。由于这些发现表明血清素（5 - HT）和章鱼胺（OA）可能会一起释放，我们研究了5 - HT和OA混合物对医用水蛭分离神经索（其中包含头部和尾部神经节）的影响。在持续灌注条件下，将50微摩尔的OA、50微摩尔的5 - HT或50微摩尔OA与50微摩尔5 - HT的混合物浴用于神经索。还进行了25或100微摩尔OA与5 - HT组合的额外实验。特别在节段性重复的背后部（DP）神经中检测神经活动，因为已证明它包含已鉴定的游泳运动单位。胺组合的非加性效应在降低DP神经的整体活动以及以虚构游泳形式改变模式化运动活动的能力方面最为明显。虽然先前已表明单独浸泡在5 - HT或OA溶液中的神经索中游泳爆发活动会增加，但我们证明这两种胺的混合物导致表达的游泳爆发次数大幅减少，并抑制已在游泳的制剂中的游泳活动。最引人注目的是观察到当用生理盐水替换胺混合物时，游泳爆发活动急剧增加。我们讨论胺混合物的作用可能是由于它们与已知触发和抑制游泳的下行中间神经元相互作用，因为在缺乏头部和尾部神经节的神经索中未观察到混合物诱导的效应。由于这两种胺的净效应并非简单相加（即已知5 - HT或OA会激活游泳，但混合物却抑制游泳），这一结果揭示了“更简单”的无脊椎动物神经系统中固有的另一层复杂性。
