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axon initial segment

Maarten Hp Kole, Romain Brette
The axon initial segment (AIS) is a unique domain of the proximal axon serving critical electrical and structural roles including the initiation of action potentials and maintenance of cellular polarity. Recent experimental and theoretical advances demonstrate that the anatomical site for initiation is remarkably diverse. The AIS location varies not only axially, along the axon, but axons also emerge variably from either the soma or proximal dendrites. Here, we review the evidence that the diversity of AIS and axon location has a substantial impact on the electrical properties and speculate that the anatomical heterogeneity of axon locations expands synaptic integration within cell types and improves information processing in neural circuits...
March 10, 2018: Current Opinion in Neurobiology
Laura F Gumy, Casper C Hoogenraad
The polarized long-distance transport of neuronal cargoes depends on the presence of functional and structural axonal subcompartments. Given the heterogeneity of neuronal cargoes, selective sorting and entry occurs in the proximal axon where multiple subcellular specializations such as the axon initial segment, the pre-axonal exclusion zone, the MAP2 pre-axonal filtering zone and the Tau diffusion barrier provide different levels of regulation. Cargoes allowed to pass through the proximal axon spread into the more distal parts...
March 3, 2018: Current Opinion in Neurobiology
Marcus K Giacci, Carole A Bartlett, Minh Huynh, Matt R Kilburn, Sarah A Dunlop, Melinda Fitzgerald
Following injury to the central nervous system, axons and myelin distinct from the initial injury site undergo changes associated with compromised function. Quantifying such changes is important to understanding the pathophysiology of neurotrauma; however, most studies to date used 2 dimensional (D) electron microscopy to analyse single sections, thereby failing to capture changes along individual axons. We used serial block face scanning electron microscopy (SBF SEM) to undertake 3D reconstruction of axons and myelin, analysing optic nerves from normal uninjured female rats and following partial optic nerve transection...
March 5, 2018: Scientific Reports
Jesse M Resnick, Gabrielle E O'Brien, Jay T Rubinstein
Since cochlear implant function involves direct depolarization of spiral ganglion neurons (SGNs) by applied current, SGN physiological health must be an important factor in cochlear implant (CI) outcomes. This expected relationship has, however, been difficult to confirm in implant recipients. Suggestively, animal studies have demonstrated both acute and progressive SGN ultrastructural changes (notably axon demyelination), even in the absence of soma death, and corresponding altered physiology following sensorineural deafening...
February 14, 2018: Hearing Research
Timothy B Esler, Robert R Kerr, Bahman Tahayori, David B Grayden, Hamish Meffin, Anthony N Burkitt
Currently, a challenge in electrical stimulation of the retina with a visual prosthesis (bionic eye) is to excite only the cells lying directly under the electrode in the ganglion cell layer, while avoiding excitation of axon bundles that pass over the surface of the retina in the nerve fiber layer. Stimulation of overlying axons results in irregular visual percepts, limiting perceptual efficacy. This research explores how differences in fiber orientation between the nerve fiber layer and ganglion cell layer leads to differences in the electrical activation of the axon initial segment and axons of passage...
2018: PloS One
Zong-Wei Yue, Ye-Lan Wang, Bo Xiao, Li Feng
Cortical dysplasia is the most common etiology of intractable epilepsy. Both excitability changes in cortical neurons and neural network reconstitution play a role in cortical dysplasia epileptogenesis. Recent research shows that the axon initial segment, a subcompartment of the neuron important to the shaping of action potentials, adjusts its position in response to changes in input, which contributes to neuronal excitability and local circuit balance. It is unknown whether axon initial segment plasticity occurs in neurons involved in seizure susceptibility in cortical dysplasia...
February 21, 2018: Neurochemical Research
Josiah R Boivin, Elly Nedivi
A rich literature describes inhibitory innervation of pyramidal neurons in terms of the distinct inhibitory cell types that target the soma, axon initial segment, or dendritic arbor. Less attention has been devoted to how localization of inhibition to specific parts of the pyramidal dendritic arbor influences dendritic signal detection and integration. The effect of inhibitory inputs can vary based on their placement on dendritic spines versus shaft, their distance from the soma, and the branch order of the dendrite they inhabit...
February 15, 2018: Current Opinion in Neurobiology
Thiri W Lin, Zhibing Tan, Arnab Barik, Dong-Min Yin, Egil Brudvik, Hongsheng Wang, Wen-Cheng Xiong, Lin Mei
GABA signaling has been implicated in neural development; however, in vivo genetic evidence is missing because mutant mice lacking GABA activity die prematurely. Here, we studied synapse development by ablating vesicular GABA transporter Vgat in in ErbB4-positive (ErbB4+) interneurons. We show that inhibitory axo-somatic synapses onto pyramidal neurons vary from one cortical layer to another; however, inhibitory synapses on axon initial segments (AISs) were similar across layers. On the other hand, PV-positive (PV+)/ErbB4+ interneurons and PV-only interneurons receive a higher number of inhibitory synapses from PV+ErbB4+ interneurons, compared with ErbB4-only interneurons...
February 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Rinki Saha, Martin Kriebel, Hansjürgen Volkmer, Gal Richter-Levin, Anne Albrecht
Activation of the amygdala is one of the hallmarks of acute stress reactions and a central element of the negative impact of stress on hippocampus-dependent memory and cognition. Stress-induced psychopathologies, such as posttraumatic stress disorder, exhibit a sustained hyperactivity of the amygdala, triggered at least in part by deficits in GABAergic inhibition that lead to shifts in amygdalo-hippocampal interaction. Here, we have utilized lentiviral knock down of neurofascin to reduce GABAergic inhibition specifically at the axon initial segment (AIS) of principal neurons within the basolateral amygdala (BLA) of rats...
February 5, 2018: Molecular Neurobiology
Martin Jacko, Sebastien M Weyn-Vanhentenryck, John W Smerdon, Rui Yan, Huijuan Feng, Damian J Williams, Joy Pai, Ke Xu, Hynek Wichterle, Chaolin Zhang
Neuronal maturation requires dramatic morphological and functional changes, but the molecular mechanisms governing this process are not well understood. Here, we studied the role of Rbfox1, Rbfox2, and Rbfox3 proteins, a family of tissue-specific splicing regulators mutated in multiple neurodevelopmental disorders. We generated Rbfox triple knockout (tKO) ventral spinal neurons to define a comprehensive network of alternative exons under Rbfox regulation and to investigate their functional importance in the developing neurons...
January 29, 2018: Neuron
Stephen L Berger, Alejandra Leo-Macias, Stephanie Yuen, Latika Khatri, Sylvia Pfennig, Yanqing Zhang, Esperanza Agullo-Pascual, Ghislaine Caillol, Min-Sheng Zhu, Eli Rothenberg, Carmen V Melendez-Vasquez, Mario Delmar, Christophe Leterrier, James L Salzer
The axon initial segment (AIS) is the site of action potential generation and a locus of activity-dependent homeostatic plasticity. A multimeric complex of sodium channels, linked via a cytoskeletal scaffold of ankyrin G and beta IV spectrin to submembranous actin rings, mediates these functions. The mechanisms that specify the AIS complex to the proximal axon and underlie its plasticity remain poorly understood. Here we show phosphorylated myosin light chain (pMLC), an activator of contractile myosin II, is highly enriched in the assembling and mature AIS, where it associates with actin rings...
February 7, 2018: Neuron
Christophe Leterrier
At the base of axons sits a unique compartment called the axon initial segment (AIS). The AIS generates and shapes the action potential before it is propagated along the axon. Neuronal excitability thus depends crucially on the AIS composition and position, and these adapt to developmental and physiological conditions. The AIS also demarcates the boundary between the somatodendritic and axonal compartments. Recent studies have brought insights into the molecular architecture of the AIS and how it regulates protein trafficking...
January 29, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yu Wang, Tuo Ji, Andrew D Nelson, Katarzyna Glanowska, Geoffrey G Murphy, Paul M Jenkins, Jack M Parent
The nonerythrocytic α-spectrin-1 (SPTAN1) gene encodes the cytoskeletal protein αII spectrin. Mutations in SPTAN1 cause early infantile epileptic encephalopathy type 5 (EIEE5); however, the role of αII spectrin in neurodevelopment and EIEE5 pathogenesis is unknown. Prior work suggests that αII spectrin is absent in the axon initial segment (AIS) and contributes to a diffusion barrier in the distal axon. Here, we have shown that αII spectrin is expressed ubiquitously in rodent and human somatodendritic and axonal domains...
January 16, 2018: Journal of Clinical Investigation
Attila Ozsvár, Róbert Szipőcs, Zoltán Ozsvár, Judith Baka, Pál Barzó, Gábor Tamás, Gábor Molnár
Degradation of myelin sheath is thought to be the cause of neurodegenerative diseases, such as multiple sclerosis (MS), but definitive agreement on mechanism of how myelin is lost is currently lacking. Autoimmune initiation of MS has been recently questioned by proposing that the immune response is a consequence of oligodendrocyte degeneration. To study the process of myelin breakdown, we induced demyelination with cuprizone and applied coherent anti-Stokes Raman scattering (CARS) microscopy, a non-destructive label-free method to image lipid structures in living tissue...
January 8, 2018: Brain Research Bulletin
Hui Liu, Peng Dong, Maria S Ioannou, Li Li, Jamien Shea, H Amalia Pasolli, Jonathan B Grimm, Patricia K Rivlin, Luke D Lavis, Minoru Koyama, Zhe Liu
Our ability to unambiguously image and track individual molecules in live cells is limited by packing of multiple copies of labeled molecules within the resolution limit. Here we devise a universal genetic strategy to precisely control copy number of fluorescently labeled molecules in a cell. This system has a dynamic range of ∼10,000-fold, enabling sparse labeling of proteins expressed at different abundance levels. Combined with photostable labels, this system extends the duration of automated single-molecule tracking by two orders of magnitude...
December 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
Frank Rattay, Hassan Bassereh, Andreas Fellner
Bipolar cells of the magnocellular pathway in the primate retina can generate action potentials because they have an axonal segment with high sodium channel density, comparable to the sodium channel band in retinal ganglion cells or pyramidal cells. The similarity between the non-human primate and the human retina is of interest for the research on retinal implants for the blind, and especially, the conditions to elicit sodium spikes in bipolar cells using extracellular stimulation. A comparison of excitation characteristics of three model neurons, a bipolar cell, a retinal ganglion cell, and a cortical pyramidal cell, demonstrates the similarities and differences regarding stimulation with microelectrodes...
December 14, 2017: Scientific Reports
Kareem Clark, Brooke A Sword, Jeffrey L Dupree
The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear...
November 2017: ASN Neuro
Rodrigo C Meza, Luciana López-Jury, Carmen C Canavier, Pablo Henny
The spontaneous tonic discharge activity of nigral dopamine neurons plays a fundamental role in dopaminergic signaling. To investigate the role of neuronal morphology and architecture with respect to spontaneous activity in this population, we visualized the 3D structure of the axon initial segment (AIS) along with the entire somatodendritic domain of adult male mouse dopaminergic neurons, previously recorded in vivo We observed a positive correlation of the firing rate with both proximity and size of the AIS...
January 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Krithika Abiraman, Anastasios V Tzingounis, George Lykotrafitis
Small conductance calcium-activated potassium (KCa 2) channels are expressed throughout the CNS and play a critical role in synaptic and neuronal excitability. KCa 2 channels have a somatodendritic distribution with their highest expression in distal dendrites. It is unclear whether KCa 2 channels are specifically present on the axon initial segment (AIS), the site at which action potentials are initiated in neurons. Through a powerful combination of toxin pharmacology, single-molecule atomic force microscopy, and dual-color fluorescence microscopy, we report here that KCa 2 channels-predominantly the KCa 2...
January 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Liudmila N Novikova, Mallappa K Kolar, Paul J Kingham, Andreas Ullrich, Sven Oberhoffner, Monika Renardy, Michael Doser, Erhard Müller, Mikael Wiberg, Lev N Novikov
Spinal cord injury (SCI) is often associated with scarring and cavity formation and therefore bridging strategies are essential to provide a physical substrate for axonal regeneration. In this study we investigated the effects of a biodegradable conduit made from trimethylene carbonate and ε-caprolactone (TC) containing poly-p-dioxanone microfilaments (PDO) with longitudinal grooves on regeneration after SCI in adult rats. In vitro studies demonstrated that different cell types including astrocytes, meningeal fibroblasts, Schwann cells and adult sensory dorsal root ganglia neurons can grow on the TC and PDO material...
January 15, 2018: Acta Biomaterialia
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