Pacemaker neurons and neuronal networks: an integrative view.

Rhythmically active neuronal networks give rise to rhythmic motor activities but also to seemingly non-rhythmic behaviors such as sleep, arousal, addiction, memory and cognition. Many of these networks contain pacemaker neurons. The ability of these neurons to generate bursts of activity intrinsically lies in voltage- and time-dependent ion fluxes resulting from a dynamic interplay among ion channels, second messenger pathways and intracellular Ca2+ concentrations, and is influenced by neuromodulators and synaptic inputs. This complex intrinsic and extrinsic modulation of pacemaker activity exerts a dynamic effect on network activity. The nonlinearity of bursting activity might enable pacemaker neurons to facilitate the onset of excitatory states or to synchronize neuronal ensembles--an interactive process that is intimately regulated by synaptic and modulatory processes.