Control of firing patterns through modulation of axon initial segment T‐type calcium channels

Non‐technical summary Spontaneous bursting, in which neurons spontaneously fire clusters of action potentials, underlies a variety of neuronal functions, including breathing and sleep rhythms. The cellular mechanisms that underlie spontaneous burst generation are poorly understood. Here, we show that calcium‐permeable ion channels, recently shown to be localized to the site of action potential initiation in the initial segment of axons, are crucial for the generation of spontaneous bursts in auditory brainstem neurons. Block of calcium influx at this site was sufficient to convert spontaneous bursting neurons into neurons which fired in a regular pattern. Block could also be mediated by the neurotransmitter dopamine, which alters calcium channel activity through a kinase dependent mechanism. These results are the first to show that spontaneous firing mode can be controlled by neuromodulators acting on a specific cellular compartment, and highlight the importance of these calcium channels in the generation of spontaneous neuronal rhythm.