The latest on the axon initial segment

This paper will review the latest results about the axon initial segment (AIS) revealing physiology details while focusing on the structural organization of the AIS. This highly specialized region of the axon is characterized, among others, by high concentrations of (particular) voltage-gated ion channels, and by highly specialized cytoskeletal networks. These repetitive and regular tiny structures (down to molecular motifs) act in synch for maintaining and modifying the functionalities associated to AIS: action potential initiation, threshold modulation, activity-dependent plasticity, assembly and maintenance, diffusion barrier (bi-directional selective filtering), etc. Significant progress in our understanding of the structural organization of the AIS has developed rapidly in recent years based on advances in high-resolution microscopy. Still, the precise ways through which the regular tiny structures observed are affecting functioning need significantly more effort. As an example here, one can look at the different voltage-gated ion channels and at their positioning, which are affecting the triggering of the action potential. When their variable densities are taken in conjunction with the regular spacing induced by the cytoskeleton, one cannot help but wonder about concepts akin to distributed amplification — which have never been put forward before in this biological context. That is why we conclude with quite a few open questions.

[1]  Greg J. Stuart,et al.  Signal Processing in the Axon Initial Segment , 2012, Neuron.

[2]  C. Nilsson,et al.  Role of the Axonal Initial Segment in Psychiatric Disorders: Function, Dysfunction, and Intervention , 2014, Front. Psychiatry.

[3]  Paul M. Jenkins,et al.  Axonal Membranes and Their Domains: Assembly and Function of the Axon Initial Segment and Node of Ranvier , 2017, Front. Cell. Neurosci..

[4]  Mark Bates,et al.  Three-Dimensional Super-Resolution Imaging by Stochastic Optical Reconstruction Microscopy , 2008, Science.

[5]  Ana I Nascimento.  The Structure and Plasticity of the Proximal Axon of Hippocampal and Dorsal Root Ganglion Neurons , 2016 .

[6]  Stefan W Hell,et al.  STED nanoscopy reveals the ubiquity of subcortical cytoskeleton periodicity in living neurons. , 2015, Cell reports.

[7]  R. Galeazzi,et al.  Node of Ranvier as an Array of Bio-Nanoantennas for Infrared Communication in Nerve Tissue , 2018, Scientific Reports.

[8]  M. Rasband,et al.  Organization of the axon initial segment: Actin like a fence , 2016, The Journal of cell biology.

[9]  Nanoscopic compartmentalization of membrane protein motion at the axon initial segment , 2016, bioRxiv.

[10]  E. Mandelkow,et al.  Axodendritic sorting and pathological missorting of Tau are isoform-specific and determined by axon initial segment architecture , 2017, The Journal of Biological Chemistry.

[11]  J. Dupree,et al.  Oxidative Stress Induces Disruption of the Axon Initial Segment , 2017, ASN Neuro.

[12]  Myosin II activity is required for structural plasticity at the axon initial segment , 2017 .

[13]  Maarten H. P. Kole,et al.  Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential , 2016, Proceedings of the National Academy of Sciences.

[14]  Matthew N. Rasband,et al.  The axon initial segment and the maintenance of neuronal polarity , 2010, Nature Reviews Neuroscience.

[15]  Jiang He,et al.  Prevalent presence of periodic actin–spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species , 2016, Proceedings of the National Academy of Sciences.

[16]  C. Schultz,et al.  Structural Plasticity of Synaptopodin in the Axon Initial Segment during Visual Cortex Development , 2017, Cerebral cortex.

[17]  C. Faivre-Sarrailh,et al.  The Kv1-associated molecules TAG-1 and Caspr2 are selectively targeted to the axon initial segment in hippocampal neurons , 2017, Journal of Cell Science.

[18]  M. Engelhardt,et al.  Activity-Dependent Axonal Plasticity in Sensory Systems , 2018, Neuroscience.

[19]  C. Morris,et al.  Action potential initiation in damaged axon initial segment , 2014, BMC Neuroscience.

[20]  T. Jegla,et al.  Neuronal polarity: an evolutionary perspective , 2015, Journal of Experimental Biology.

[21]  Matthew N. Rasband,et al.  Developmental Changes in Expression of βIV Spectrin Splice Variants at Axon Initial Segments and Nodes of Ranvier , 2017, Front. Cell. Neurosci..

[22]  A. T. Gulledge,et al.  Neuron Morphology Influences Axon Initial Segment Plasticity123 , 2016, eNeuro.

[23]  M. Evans,et al.  Evaluating Tools for Live Imaging of Structural Plasticity at the Axon Initial Segment , 2016, Front. Cell. Neurosci..

[24]  M. Kreutz,et al.  The Segregated Expression of Voltage-Gated Potassium and Sodium Channels in Neuronal Membranes: Functional Implications and Regulatory Mechanisms , 2017, Front. Cell. Neurosci..

[25]  Yihao Zhang,et al.  Modeling of the axon membrane skeleton structure and implications for its mechanical properties , 2017, PLoS Comput. Biol..

[26]  Rei Yamada,et al.  Structural and Functional Plasticity at the Axon Initial Segment , 2016, Front. Cell. Neurosci..

[27]  W. N. Ross,et al.  Imaging with organic indicators and high-speed charge-coupled device cameras in neurons: some applications where these classic techniques have advantages , 2014, Neurophotonics.

[28]  Christophe Leterrier,et al.  Nanoscale architecture of the axon initial segment reveals an organized and robust scaffold , 2015, bioRxiv.

[29]  Christophe Leterrier,et al.  Ankyrin G Membrane Partners Drive the Establishment and Maintenance of the Axon Initial Segment , 2016, bioRxiv.

[30]  P. Wahle,et al.  Heterogeneity of the Axon Initial Segment in Interneurons and Pyramidal Cells of Rodent Visual Cortex , 2017, Front. Cell. Neurosci..

[31]  STORMing towards a clear picture of the cytoskeleton in neurons , 2015, eLife.

[32]  Steven L Jones,et al.  Axon Initial Segment Cytoskeleton: Architecture, Development, and Role in Neuron Polarity , 2016, Neural plasticity.

[33]  K. Bender,et al.  Periadolescent Maturation of GABAergic Hyperpolarization at the Axon Initial Segment. , 2017, Cell reports.

[34]  I. Fleidervish,et al.  Functional implications of axon initial segment cytoskeletal disruption in stroke , 2015, Acta Pharmacologica Sinica.

[35]  Myung Chul Choi,et al.  Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment , 2016, Nature Communications.

[36]  C. Hoogenraad,et al.  Cooperative Interactions between 480 kDa Ankyrin-G and EB Proteins Assemble the Axon Initial Segment , 2016, The Journal of Neuroscience.

[37]  J. Burrone,et al.  Homeostatic Plasticity of Subcellular Neuronal Structures: From Inputs to Outputs , 2016, Trends in Neurosciences.

[38]  Steven L Jones,et al.  Axon initial segment cytoskeleton comprises a multiprotein submembranous coat containing sparse actin filaments , 2014, The Journal of cell biology.

[39]  S. Dib-Hajj,et al.  Preferential Targeting of Nav1.6 Voltage-Gated Na+ Channels to the Axon Initial Segment during Development , 2015, PloS one.

[40]  Christophe Leterrier,et al.  The Axon Initial Segment, 50Years Later: A Nexus for Neuronal Organization and Function. , 2016, Current topics in membranes.

[41]  M. Rasband,et al.  Subcellular patterning: axonal domains with specialized structure and function. , 2015, Developmental cell.

[42]  R. Adachi,et al.  Redistribution of Kv1 and Kv7 enhances neuronal excitability during structural axon initial segment plasticity , 2015, Nature Communications.

[43]  A. Burlingame,et al.  αII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is Required for Nervous System Function , 2017, The Journal of Neuroscience.

[44]  Richard Kempter,et al.  Spikelets in Pyramidal Neurons: Action Potentials Initiated in the Axon Initial Segment That Do Not Activate the Soma , 2017, PLoS Comput. Biol..

[45]  Thomas Deller,et al.  Loss of the cisternal organelle in the axon initial segment of cortical neurons in synaptopodin‐deficient mice , 2007, The Journal of comparative neurology.

[46]  W.R. Hewlett,et al.  Distributed Amplification , 1948, Proceedings of the IRE.