School of Psychology and Neuroscience, University of St Andrews, St Andrews, Fife, United Kingdom.
J Neurophysiol. 2014 Feb;111(3):659-74. doi: 10.1152/jn.00378.2013. Epub 2013 Nov 20.
Spinal motor control networks are regulated by neuromodulatory systems to allow adaptability of movements. The present study aimed to elucidate the role of nitric oxide (NO) in the modulation of mammalian spinal locomotor networks. This was investigated with isolated spinal cord preparations from neonatal mice in which rhythmic locomotor-related activity was induced pharmacologically. Bath application of the NO donor diethylamine NONOate (DEA/NO) decreased the frequency and modulated the amplitude of locomotor-related activity recorded from ventral roots. Removal of endogenous NO with coapplication of a NO scavenger (PTIO) and a nitric oxide synthase (NOS) blocker [nitro-l-arginine methyl ester (l-NAME)] increased the frequency and decreased the amplitude of locomotor-related activity. This demonstrates that endogenously derived NO can modulate both the timing and intensity of locomotor-related activity. The effects of DEA/NO were mimicked by the cGMP analog 8-bromo-cGMP. In addition, the soluble guanylyl cyclase (sGC) inhibitor ODQ blocked the effects of DEA/NO on burst amplitude and frequency, although the frequency effect was only blocked at low concentrations of DEA/NO. This suggests that NO-mediated modulation involves cGMP-dependent pathways. Sources of NO were studied within the lumbar spinal cord during postnatal development (postnatal days 1-12) with NADPH-diaphorase staining. NOS-positive cells in the ventral horn exhibited a rostrocaudal gradient, with more cells in rostral segments. The number of NOS-positive cells was also found to increase during postnatal development. In summary, we have shown that NO, derived from sources within the mammalian spinal cord, modulates the output of spinal motor networks and is therefore likely to contribute to the fine-tuning of locomotor behavior.
脊髓运动控制网络受神经调质系统调节，以允许运动的适应性。本研究旨在阐明一氧化氮（NO）在调节哺乳动物脊髓运动网络中的作用。这是通过在新生小鼠的离体脊髓标本中进行研究的，其中通过药理学诱导产生节律性运动相关活动。NO 供体二乙胺 NONO 酸盐（DEA/NO）的浴应用降低了记录自腹根的运动相关活动的频率并调节其幅度。内源性 NO 的去除与内源性 NO 清除剂（PTIO）和一氧化氮合酶（NOS）阻断剂 [硝基-l-精氨酸甲酯（l-NAME）] 的共应用增加了运动相关活动的频率并降低了其幅度。这表明内源性衍生的 NO 可以调节运动相关活动的时间和强度。DEA/NO 的作用被 cGMP 类似物 8-溴-cGMP 模拟。此外，可溶性鸟苷酸环化酶（sGC）抑制剂 ODQ 阻断了 DEA/NO 对爆发幅度和频率的影响，尽管仅在 DEA/NO 的低浓度下阻断了频率效应。这表明 NO 介导的调节涉及 cGMP 依赖性途径。在出生后发育期间（出生后 1-12 天）在腰椎脊髓中研究了 NO 的来源，用 NADPH 黄递酶染色。腹角中的 NOS 阳性细胞表现出头尾梯度，在头段有更多的细胞。还发现 NOS 阳性细胞的数量在出生后发育过程中增加。总之，我们已经表明，源自哺乳动物脊髓内的 NO 调节脊髓运动网络的输出，因此可能有助于运动行为的微调。
