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Published on: May 25, 2011
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Sodium channel endocytosis drives axon initial segment plasticity
Amélie Fréal1,2, Nora Jamann1,2, Jolijn Ten Bos2
1Axonal Signaling Group, Netherlands Institute for Neurosciences (NIN), Royal Netherlands Academy for Arts and Sciences (KNAW), Amsterdam, Netherlands.
Science Advances
|September 15, 2023
Summary
Neurons adapt to network activity through changes at the axon initial segment (AIS). NMDA receptor activation rapidly removes sodium channels from the AIS, increasing the action potential threshold.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Activity-dependent plasticity allows neurons to adjust their electrical output.
- The axon initial segment (AIS) is crucial for action potential initiation, relying on clustered sodium channels.
- Molecular mechanisms governing AIS plasticity and sodium channel regulation are not well understood.
Purpose of the Study:
- To investigate the nanoscale organization and plasticity of the axon initial segment (AIS).
- To elucidate the molecular mechanisms underlying activity-dependent regulation of AIS sodium channels.
Main Methods:
- Development of genetic tools for labeling endogenous sodium channels and scaffolding proteins.
- Longitudinal imaging of AIS plasticity in hippocampal neurons (in slices and primary cultures).
- Utilizing N-methyl-d-aspartate receptor activation as a stimulus.
Main Results:
- NMDA receptor activation induces both long-term synaptic depression and rapid internalization of AIS sodium channels.
- Sodium channel internalization occurs via clathrin-mediated endocytosis at the distal AIS.
- This internalization event leads to an increased threshold for action potential generation.
Conclusions:
- A fundamental mechanism for rapid, activity-dependent reorganization of the AIS has been identified.
- Plasticity of intrinsic neuronal excitability shares conserved features with synaptic plasticity.
- This study provides insights into how neurons adapt their firing properties in response to network activity.
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