Hotchkiss Brain Institute, Departments of Comparative Biology and Experimental Medicine, Physiology and Pharmacology, and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
J Neurophysiol. 2012 Dec;108(12):3370-81. doi: 10.1152/jn.00482.2012. Epub 2012 Sep 19.
Monoamines can modulate the output of a variety of invertebrate and vertebrate networks, including the spinal cord networks that control walking. Here we examined the multiple changes in the output of locomotor networks induced by dopamine (DA). We found that DA can depress the activation of locomotor networks in the neonatal mouse spinal cord following ventral root stimulation. By examining disinhibited rhythms, where the Renshaw cell pathway was blocked, we found that DA depresses a putative recurrent excitatory pathway that projects onto rhythm-generating circuitry of the spinal cord. This depression was D(2) but not D(1) receptor dependent and was not due exclusively to depression of excitatory drive to motoneurons. Furthermore, the depression in excitation was not dependent on network activity. We next compared the modulatory effects of DA on network function by focusing on a serotonin and a N-methyl-dl-aspartate-evoked rhythm. In contrast to the depressive effects on a ventral root-evoked rhythm, we found that DA stabilized a drug-evoked rhythm, reduced the frequency of bursting, and increased amplitude. Overall, these data demonstrate that DA can potentiate network activity while at the same time reducing the gain of recurrent excitatory feedback loops from motoneurons onto the network.
单胺类物质可以调节多种无脊椎动物和脊椎动物网络的输出，包括控制行走的脊髓网络。在这里，我们研究了多巴胺 (DA) 引起的运动网络输出的多种变化。我们发现，DA 可以抑制新生儿小鼠脊髓腹根刺激后的运动网络激活。通过检查去抑制节律（阻断 Renshaw 细胞通路），我们发现 DA 抑制了一种投射到脊髓节律产生电路的假定的复发性兴奋性通路。这种抑制是 D2 而不是 D1 受体依赖性的，并且不仅仅是由于对运动神经元的兴奋性驱动的抑制。此外，兴奋的抑制不依赖于网络活动。接下来，我们通过关注 5-羟色胺和 N-甲基-dl-天冬氨酸诱发的节律，比较了 DA 对网络功能的调制作用。与对腹根诱发节律的抑制作用相反，我们发现 DA 稳定了药物诱发的节律，降低了爆发的频率，并增加了幅度。总的来说，这些数据表明，DA 可以增强网络活动，同时降低来自运动神经元的复发性兴奋性反馈回路对网络的增益。
