Essential role of astrocytes in rapid activity-dependent restructuration of the axon initial segment

One key regulator of neuronal excitability is the axon initial segment (AIS), a highly specialized axonal region, enriched in ion channels, where action potentials are initiated. The AIS can undergo significant morphological changes to fine-tune neuronal excitability in response to external perturbations. Long considered solely a homeostatic mechanism operating over long timescales (hours to days) to adjust excitability, we show here that this phenomenon can also occur rapidly, within minutes, following a brief period of high activity in layer 5 pyramidal neurons of the visual cortex. Because astrocytes have been known to regulate neuronal excitability, we explored the effects of gliotransmitters on this process and identified the calcium-binding protein S100β from astrocytes to be required for the rapid reorganization of the AIS.