Convergent comodulation: Rules and influence on circuit output

Neural circuits are continuously under the influence of multiple chemical neuromodulators. The prevalent view is that neuromodulation increases the flexibility of circuit output. However, different modulators can have overlapping cellular and subcellular targets, and thus convergence and occlusion may limit the repertoire of possible circuit states. We propose a complementary view that convergent comodulation may result in a more consistent circuit activity that, with increasing numbers of modulators, becomes less dependent on the specific identity of the modulators involved. We examine this hypothesis in the crustacean stomatogastric ganglion, where multiple excitatory neuropeptides activate the same ionic current and have similar effects on synapses.