Neuromodulation of neurons and synapses

•Modulation of synaptic strength can occur through changes in short-term plasticity.•Modulators can shape or induce long-term synaptic plasticity.•Modulators can have spatially specific and divergent targets in single neurons.•Modulators can change neuronal excitability qualitatively and nonlinearly.•Classical ionotropic receptors can exert unambiguously modulatory effects.

Neuromodulation underlies the flexibility of neural circuit operation and behavior. Individual neuromodulators can have divergent actions in a neuron by targeting multiple physiological mechanisms. Conversely, multiple neuromodulators may have convergent actions through overlapping targets. The divergent and convergent neuromodulator actions can be unambiguously synergistic or antagonistic, but neuromodulation often entails balanced adjustment of nonlinear membrane and synaptic properties by targeting ion channel and synaptic dynamics rather than just excitability or synaptic strength. In addition, neuromodulators can exert effects at multiple timescales, from short-term adjustments of neuron and synapse function to persistent long-term regulation. This short review summarizes some highlights of the diverse actions of neuromodulators on ion channel and synaptic properties.