New study on Axon Initial Segment plasticity in Science Advances

24 September 2023

A new study led by Amelie Freal (FGA) describes mechanisms controlling Axon Initial Segment plasticity, revealing distinct and dynamic pools of sodium channels that adjust neuronal excitability

Axon Initial Segment (AIS) plasticity is a crucial process for neuronal homeostasis, as it allows neurons to adapt action potentials output to changes in network activity. The initiation and shape of action potential initiation relies on the clustering of voltage-gated sodium channels at the AIS, but how those channels reorganize during plasticity remain largely elusive.
In this study, we have engineered genetic tools to label endogenous sodium channels and their associated scaffolding proteins. This approach allowed us to uncover their nanoscale organization and longitudinally image AIS plasticity in hippocampal neurons.

Our results reveal that NMDA receptors activation triggers both synaptic depression and AIS plasticity. Notably, the distal pool of sodium channels is endocytosed, and this reduction in AIS length is associated with a decrease in neuronal excitability.
Our data reveal a fundamental mechanism for rapid activity-dependent AIS reorganization and suggests that plasticity of intrinsic excitability shares conserved features with synaptic plasticity.

The paper can be found here