neuromodulation;
peptide;
central pattern generator;
stomatogastric;
期刊名称：
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
i s s n：
0270-6474
年卷期：
2018 年
38 卷
40 期
页 码：
8549-8562
页 码：
摘 要：
Multiple neuromodulators act in concert to shape the properties of neural circuits. Different neuromodulators usually activate distinct receptors but can have overlapping targets. Therefore, circuit output depends on neuromodulator interactions at shared targets, a poorly understood process. We explored quantitative rules of co-modulation of two principal targets of neuromodulation: synapses and voltage-gated ionic currents. In the stomatogastric ganglion of the male crab Cancer borealis, the neuropeptides proctolin (Proc) and the crustacean cardioactive peptide (CCAP) modulate synapses of the pyloric circuit and activate a voltage-gated current (I-MI) in multiple neurons. We examined the validity of a simple dose-dependent quantitative rule, that co-modulation by Proc and CCAP is predicted by the linear sum of the individual effects of each modulator up to saturation. We found that this rule is valid for co-modulation of synapses, but not for the activation of I-MI , in which co-modulation was sublinear. The predictions for the co-modulation of I-MI activation were greatly improved if we assumed that the intracellular pathways activated by two peptide receptors inhibit one another. These findings suggest that the pathways activated by two neuromodulators could have distinct interactions, leading to distinct co-modulation rules for different targets even in the same neuron. Given the evolutionary conservation of neuromodulator receptors and signaling pathways, such distinct rules for co-modulation of different targets are likely to be common across neuronal circuits.
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