• The dynamic axon initial segme...

*Result*: The dynamic axon initial segment: From neuronal polarity to network homeostasis.

Title:
The dynamic axon initial segment: From neuronal polarity to network homeostasis.
Authors:
Fréal A; Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Amsterdam, the Netherlands., Hoogenraad CC; Department of Neuroscience, Genentech, Inc, South San Francisco, CA 94080, USA. Electronic address: hoogenraad.casper@gene.com.
Source:
Neuron [Neuron] 2025 Mar 05; Vol. 113 (5), pp. 649-669. Date of Electronic Publication: 2025 Feb 12.
Publication Type:
Journal Article; Review
Language:
English
Journal Info:
Publisher: Cell Press Country of Publication: United States NLM ID: 8809320 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4199 (Electronic) Linking ISSN: 08966273 NLM ISO Abbreviation: Neuron Subsets: MEDLINE
Imprint Name(s):
Original Publication: [Cambridge, Mass. : Cell Press, c1988-
MeSH Terms:
Homeostasis*/physiology , Axon Initial Segment*/physiology , Neuronal Plasticity*/physiology , Cell Polarity*/physiology , Neurons*/physiology , Neurons*/cytology , Nerve Net*/physiology , Axons*/physiology, Action Potentials/physiology ; Animals ; Humans
Contributed Indexing:
Keywords: AIS; actin; ankyrin; axon initial segment; microtubule; neurological disease; neuron; plasticity; self-organization; synapse; transport
Entry Date(s):
Date Created: 20250213 Date Completed: 20250507 Latest Revision: 20250507
Update Code:
20260130
DOI:
10.1016/j.neuron.2025.01.004
PMID:
39947181
Database:
MEDLINE

*Further Information*

*The axon initial segment (AIS) is a highly specialized compartment in neurons that resides in between axonal and somatodendritic domains. The localization of the AIS in the proximal part of the axon is essential for its two major functions: generating and modulating action potentials and maintaining neuron polarity. Recent findings revealed that the incredibly stable AIS is generated from highly dynamic components and can undergo extensive structural and functional changes in response to alterations in activity levels. These activity-dependent alterations of AIS structure and function have profound consequences for neuronal functioning, and AIS plasticity has emerged as a key regulator of network homeostasis. This review highlights the functions of the AIS, its architecture, and how its organization and remodeling are influenced by developmental plasticity and both acute and chronic adaptations. It also discusses the mechanisms underlying these processes and explores how dysregulated AIS plasticity may contribute to brain disorders.
(Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)*

*Declaration of interests C.C.H. is an employee of Genentech, Inc., a member of the Roche group.*