Brustein Edna, Drapeau Pierre
Center for Research in Neuroscience, Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada H3G 1A4.
J Neurosci. 2005 Nov 16;25(46):10607-16. doi: 10.1523/JNEUROSCI.2017-05.2005.
During development, neural networks progress through important functional changes such as the generation of spontaneous activity, the expression of a depolarizing chloride gradient, and the appearance of neuromodulation. Little is known about how these processes are integrated to yield mature behaviors. We showed previously that, during the maturation of the locomotor network of the zebrafish, endogenous serotonin (5HT) increased motor activity by reducing intervals of inactivity, without affecting the active swim periods that are the target of 5HT in other and more mature preparations. Because membrane properties were constant during the rest intervals, we examined here whether 5HT modulates chloride homeostasis. We compared the effects of blocking (inward) chloride cotransport with bumetanide to the effects of 5HT and its antagonists, both behaviorally by video imaging and cellularly by whole-cell and gramicidin-perforated patch recordings. Bumetanide mimicked the effects of 5HT antagonists, by prolonging rest intervals without affecting the properties of swim episodes (duration; frequency; extent of depolarization) either behaviorally or during fictive swimming. Furthermore, bumetanide and 5HT antagonists suppressed the amplitude of depolarizing responses evoked by ionophoresis of glycine onto spinal neurons in the presence of tetrodotoxin and transiently suppressed the amplitude of responses to glycine measured after fictive swimming. The effects of bumetanide contrasted with and occluded the effects of 5HT. We suggest that, during development, endogenous 5HT modulates chloride homeostasis during the quiescent intervals and thereby offsets the long periods of quiescence commonly observed in developing networks to allow expression of sustained and behaviorally relevant activity.
在发育过程中，神经网络会经历重要的功能变化，如自发活动的产生、去极化氯离子梯度的表达以及神经调节的出现。对于这些过程如何整合以产生成熟行为，我们知之甚少。我们之前表明，在斑马鱼运动网络成熟过程中，内源性血清素（5HT）通过减少静止间隔来增加运动活性，而不影响在其他更成熟的标本中作为5HT作用靶点的主动游泳期。由于在静止间隔期间膜特性保持恒定，我们在此研究5HT是否调节氯离子稳态。我们通过视频成像在行为学上以及通过全细胞和短杆菌肽穿孔膜片钳记录在细胞水平上比较了用布美他尼阻断（内向）氯离子共转运的效果与5HT及其拮抗剂的效果。布美他尼模拟了5HT拮抗剂的作用，通过延长静止间隔，而在行为学上或在虚拟游泳期间均不影响游泳发作的特性（持续时间、频率、去极化程度）。此外，布美他尼和5HT拮抗剂在存在河豚毒素的情况下抑制了甘氨酸离子导入脊髓神经元所诱发的去极化反应的幅度，并短暂抑制了虚拟游泳后测得的对甘氨酸反应的幅度。布美他尼的作用与5HT的作用形成对比并掩盖了5HT的作用。我们认为，在发育过程中，内源性5HT在静止间隔期间调节氯离子稳态，从而抵消发育中的网络中常见的长时间静止，以允许表达持续的和与行为相关的活性。
