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https://www.readbyqxmd.com/read/29337302/critical-roles-of-%C3%AE-ii-spectrin-in-brain-development-and-epileptic-encephalopathy
#1
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
https://www.readbyqxmd.com/read/29325992/quantitative-analysis-of-lipid-debris-accumulation-caused-by-cuprizone-induced-myelin-degradation-in-different-cns-areas
#2
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
https://www.readbyqxmd.com/read/29284749/visualizing-long-term-single-molecule-dynamics-in-vivo-by-stochastic-protein-labeling
#3
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
https://www.readbyqxmd.com/read/29242502/impact-of-electrode-position-on-the-elicitation-of-sodium-spikes-in-retinal-bipolar-cells
#4
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
https://www.readbyqxmd.com/read/29228786/oxidative-stress-induces-disruption-of-the-axon-initial-segment
#5
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
https://www.readbyqxmd.com/read/29217687/role-of-the-axon-initial-segment-in-the-control-of-spontaneous-frequency-of-nigral-dopaminergic-neurons-in-vivo
#6
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...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29180442/kca2-channel-localization-and-regulation-in-the-axon-initial-segment
#7
Krithika Abiraman, Anastasios V Tzingounis, George Lykotrafitis
Small conductance calcium-activated potassium (KCa2) channels are expressed throughout the CNS and play a critical role in synaptic and neuronal excitability. KCa2 channels have a somatodendritic distribution with their highest expression in distal dendrites. It is unclear whether KCa2 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 KCa2 channels-predominantly the KCa2...
November 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29174588/trimethylene-carbonate-caprolactone-conduit-with-poly-p-dioxanone-microfilaments-to-promote-regeneration-after-spinal-cord-injury
#8
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...
November 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29170630/heterogeneity-of-the-axon-initial-segment-in-interneurons-and-pyramidal-cells-of-rodent-visual-cortex
#9
Felix Höfflin, Alexander Jack, Christian Riedel, Julia Mack-Bucher, Johannes Roos, Corinna Corcelli, Christian Schultz, Petra Wahle, Maren Engelhardt
The microdomain that orchestrates action potential initiation in neurons is the axon initial segment (AIS). It has long been considered to be a rather homogeneous domain at the very proximal axon hillock with relatively stable length, particularly in cortical pyramidal cells. However, studies in other brain regions paint a different picture. In hippocampal CA1, up to 50% of axons emerge from basal dendrites. Further, in about 30% of thick-tufted layer V pyramidal neurons in rat somatosensory cortex, axons have a dendritic origin...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29167400/tonotopic-variation-of-the-t-type-ca2-current-in-avian-auditory-coincidence-detector-neurons
#10
Ryota Fukaya, Rei Yamada, Hiroshi Kuba
Neurons in avian nucleus laminaris (NL) are binaural coincidence detectors for sound localization and are characterized by striking structural variations in dendrites and axon initial segment (AIS) according to their acoustic tuning (characteristic frequency, CF). T-type Ca2+ (CaT) channels regulate synaptic integration and firing behavior at these neuronal structures. However, whether or how CaT channels contribute to the signal processing in NL neurons is not known. In this study, we addressed this issue with whole-cell recording and two-photon Ca2+ imaging in brain slices of posthatch chicks of both sexes...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29136108/perturbation-of-gabaergic-synapses-at-the-axon-initial-segment-of-basolateral-amygdala-induces-trans-regional-metaplasticity-at-the-medial-prefrontal-cortex
#11
Rinki Saha, Kuldeep Shrivastava, Liang Jing, Rachel Schayek, Mouna Maroun, Martin Kriebel, Hansjürgen Volkmer, Gal Richter-Levin
GABAergic synapses in the basolateral amygdala (BLA) play an important role in fear memory generation. We have previously reported that reduction in GABAergic synapses innervating specifically at the axon initial segment (AIS) of principal neurons of BLA, by neurofascin (NF) knockdown, impairs fear extinction. BLA is bidirectionally connected with the medial prefrontal cortex (mPFC), which is a key region involved in extinction of acquired fear memory. Here, we showed that reducing AIS GABAergic synapses within the BLA leads to impairment of synaptic plasticity in the BLA-mPFC pathway, as well as in the ventral subiculum (vSub)-mPFC pathway, which is independent of BLA involvement...
November 9, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29109270/m-current-inhibition-rapidly-induces-a-unique-ck2-dependent-plasticity-of-the-axon-initial-segment
#12
Jonathan Lezmy, Maya Lipinsky, Yana Khrapunsky, Eti Patrich, Lia Shalom, Asher Peretz, Ilya A Fleidervish, Bernard Attali
Alterations in synaptic input, persisting for hours to days, elicit homeostatic plastic changes in the axon initial segment (AIS), which is pivotal for spike generation. Here, in hippocampal pyramidal neurons of both primary cultures and slices, we triggered a unique form of AIS plasticity by selectively targeting M-type K(+) channels, which predominantly localize to the AIS and are essential for tuning neuronal excitability. While acute M-current inhibition via cholinergic activation or direct channel block made neurons more excitable, minutes to hours of sustained M-current depression resulted in a gradual reduction in intrinsic excitability...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29093056/first-person-richard-eva
#13
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Richard Eva is the first author on 'EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment', published in Journal of Cell Science. Richard is a research associate in the laboratory of Prof. James Fawcett, investigating the intrinsic mechanisms preventing brain and spinal cord axons from regenerating after injury in order to identify novel strategies for enhancing repair...
November 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29079505/a-constitutively-active-ikk-complex-at-the-axon-initial-segment
#14
Hans-Georg König, Orla Watters, Sinéad Kinsella, Mohammed Ameen, Beau J Fenner, Jochen H M Prehn
BACKGROUND: Previous studies provided evidence for an accumulation of IκB-kinase (IKK) α/β at the axon initial segment (AIS), a neuronal compartment defined by ankyrin-G expression. Here we explored whether the presence of the IKK-complex at the AIS was associated with the activation of IKK signaling at this site. METHODS AND RESULTS: Proximity-ligation assays (PLAs) using pan-IKK α/β, phospho-IKK α/β -specific as well as ankyrin-G specific antibodies validated their binding to proximal epitopes in the AIS, while antibodies to other phosphorylated signaling proteins showed no preference for the AIS...
October 24, 2017: Brain Research
https://www.readbyqxmd.com/read/29060460/a-continuum-model-of-electrical-stimulation-of-multi-compartmental-retinal-ganglion-cells
#15
Abdulrahman Alqahtani, Amr Al Abed, Tianruo Guo, Nigel H Lovell, Socrates Dokos
A continuum multi-domain model of electrical stimulation of the retina is presented. Each point in the retinal ganglion cell layer could be thought of as representing a single cell, whose biophysics is described using a four-compartment formulation incorporating varying ion channel expressions in the soma, axon initial segment, dendrites and axon. Our continuum model was validated against a discrete morphologically-realistic OFF RGC model, using intra- and extra-cellular electrical stimulation scenarios. Simulations from the continuum model reproduced the same results as that of the discrete model...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29055053/expression-patterns-of-ion-channels-and-structural-proteins-in-a-multimodal-cell-type-of-the-avian-optic-tectum
#16
Katharina Lischka, Simone Ladel, Harald Luksch, Stefan Weigel
The midbrain is an important subcortical area involved in distinct functions such as multimodal integration, movement initiation, bottom-up and top-down attention. Our group is particularly interested in cellular computation of multisensory integration. We focus on the visual part of the avian midbrain, the optic tectum (TeO, counterpart to mammalian superior colliculus). This area has a layered structure with the great advantage of distinct in- and output regions. In chicken, the TeO is organized in 15 layers where visual input targets the superficial layers while auditory input terminates in deeper layers...
October 21, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29042434/trafficking-of-kv2-1-channels-to-the-axon-initial-segment-by-a-novel-non-conventional-secretory-pathway
#17
Camilla Stampe Jensen, Shoji Watanabe, Jeroen Ingrid Stas, Jessica Klaphaak, Ayaka Yamane, Nicole Schmitt, Søren-Peter Olesen, James S Trimmer, Hanne Borger Rasmussen, Hiroaki Misonou
Kv2.1 is a major delayed rectifier voltage-gated potassium channel widely expressed in neurons of the central nervous system. Kv2.1 localizes in high-density cell surface clusters in the soma and proximal dendrites as well as in the axon initial segment. Given the crucial roles of both of these compartments in integrating signal input and then generating output, this localization of Kv2.1 is ideal for regulating the overall excitability of neurons. Here we used fluorescence recovery after photobleaching (FRAP) imaging, mutagenesis and pharmacological interventions to investigate the molecular mechanisms that control the localization of Kv2...
October 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29038243/an-%C3%AE-ii-spectrin-based-cytoskeleton-protects-large-diameter-myelinated-axons-from-degeneration
#18
Claire Yu-Mei Huang, Chuansheng Zhang, Daniel R Zollinger, Christophe Leterrier, Matthew N Rasband
Axons must withstand mechanical forces including tension, torsion, and compression. Spectrins and actin form a periodic cytoskeleton proposed to protect axons against these forces. However, since spectrins also participate in assembly of axon initial segments (AIS) and nodes of Ranvier, it is difficult to uncouple their roles in maintaining axon integrity from their functions at AIS and nodes. To overcome this problem and to determine the importance of spectrin cytoskeletons for axon integrity, we generated mice with αII spectrin-deficient peripheral sensory neurons...
October 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29038240/%C3%AE-ii-spectrin-forms-a-periodic-cytoskeleton-at-the-axon-initial-segment-and-is-required-for-nervous-system-function
#19
Claire Yu-Mei Huang, Chuansheng Zhang, Tammy Szu-Yu Ho, Juan Oses-Prieto, Alma L Burlingame, Joshua Lalonde, Jeffrey L Noebels, Christophe Leterrier, Matthew N Rasband
Spectrins form a submembranous cytoskeleton proposed to confer strength and flexibility to neurons and to participate in ion channel clustering at axon initial segments (AIS) and nodes of Ranvier. Neuronal spectrin cytoskeletons consist of diverse β subunits and αII spectrin. Although αII spectrin is found in neurons in both axonal and somatodendritic domains, using proteomics, biochemistry, and super-resolution microscopy we show that αII and βIV spectrin interact and form a periodic AIS cytoskeleton...
October 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28993757/painful-and-prolonged-muscle-cramps-following-insulin-injections-in-a-patient-with-type-2-diabetes-mellitus-revisiting-the-1992-duke-case
#20
Rami A Ballout, Asma Arabi
A 56-year-old middle-eastern male with a long-standing history of poorly controlled type 2 diabetes mellitus presented to us complaining of severely painful bilateral upper and lower extremity cramps occurring shortly after his rapid-acting insulin analog injection(s). The cramps had started 6 months ago and have been occurring intermittently in non-predictable episodes since then. He had otherwise never experienced any insulin-related adverse reaction(s) before. His cramps are very painful and debilitating, interfering with his daily activities and placing him in a state of constant fear/anxiety of re-experiencing them...
2017: Frontiers in Endocrinology
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