Adaptation of an organism to its changing environment ultimately depends on the modification of neuronal activity. The dynamic interaction between cellular components within neuronal networks relies on fast synaptic interaction via ionotropic receptors. However, neuronal networks are also subject to modulation mediated by various metabotropic G-protein-coupled receptors that modify synaptic and neuronal function. Modulation increases the functional complexity of a network, because the same cellular components can produce different outputs depending on the behavioural state of the animal. This review, which is part of the TINS Microcircuits Special Feature, provides an overview of neuromodulation in two neuronal circuits that both produce oscillatory activity but differ fundamentally in function. Hippocampal circuits are compared with the spinal networks generating locomotion, with a view to exploring common principles of neuromodulatory activity.