Sodium channel endocytosis drives axon initial segment plasticity

Amélie Fréal, Nora Jamann, Jolijn Ten Bos, Jacqueline Jansen, Naomi Petersen, Thijmen Ligthart, Casper C Hoogenraad, Maarten H P Kole

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

10 Downloads (Pure)


Activity-dependent plasticity of the axon initial segment (AIS) endows neurons with the ability to adapt action potential output to changes in network activity. Action potential initiation at the AIS highly depends on the clustering of voltage-gated sodium channels, but the molecular mechanisms regulating their plasticity remain largely unknown. Here, we developed genetic tools to label endogenous sodium channels and their scaffolding protein, to reveal their nanoscale organization and longitudinally image AIS plasticity in hippocampal neurons in slices and primary cultures. We find that N-methyl-d-aspartate receptor activation causes both long-term synaptic depression and rapid internalization of AIS sodium channels within minutes. The clathrin-mediated endocytosis of sodium channels at the distal AIS increases the threshold for action potential generation. These data reveal a fundamental mechanism for rapid activity-dependent AIS reorganization and suggests that plasticity of intrinsic excitability shares conserved features with synaptic plasticity.

Originele taal-2Engels
Pagina's (van-tot)eadf3885
TijdschriftScience advances
Nummer van het tijdschrift37
StatusGepubliceerd - 15 sep. 2023


Duik in de onderzoeksthema's van 'Sodium channel endocytosis drives axon initial segment plasticity'. Samen vormen ze een unieke vingerafdruk.

Citeer dit