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https://www.readbyqxmd.com/read/28441389/the-basis-of-sharp-spike-onset-in-standard-biophysical-models
#1
Maria Telenczuk, Bertrand Fontaine, Romain Brette
In most vertebrate neurons, spikes initiate in the axonal initial segment (AIS). When recorded in the soma, they have a surprisingly sharp onset, as if sodium (Na) channels opened abruptly. The main view stipulates that spikes initiate in a conventional manner at the distal end of the AIS, then progressively sharpen as they backpropagate to the soma. We examined the biophysical models used to substantiate this view, and we found that spikes do not initiate through a local axonal current loop that propagates along the axon, but through a global current loop encompassing the AIS and soma, which forms an electrical dipole...
2017: PloS One
https://www.readbyqxmd.com/read/28440877/bdnf-nt3-regulate-ais-location-and-affect-neuronal-excitability-in-cultured-hippocampal-neurons
#2
Yu Guo, Zi-Jun Su, Yi-Kun Chen, Zhen Chai
Plasticity of the axon initial segment (AIS) has aroused great interest in recent years because it regulates action potential initiation and neuronal excitability. AIS plasticity manifests as modulation of ion channels or variation in AIS structure. However, the mechanisms underlying structural plasticity of the AIS are not well understood. Here, we combined immunofluorescence, patch-clamp recordings, and pharmacological methods in cultured hippocampal neurons to investigate the factors participating in AIS structural plasticity during development...
April 25, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28436546/corrigendum-the-impact-of-early-environmental-interventions-on-structural-plasticity-of-the-axon-initial-segment-in-neocortex-m-nozari-t-suzuki-m-g-p-rosa-k-yamakawa-and-n-atapour
#3
(no author information available yet)
No abstract text is available yet for this article.
April 24, 2017: Developmental Psychobiology
https://www.readbyqxmd.com/read/28426968/map2-defines-a-pre-axonal-filtering-zone-to-regulate-kif1-versus-kif5-dependent-cargo-transport-in-sensory-neurons
#4
Laura F Gumy, Eugene A Katrukha, Ilya Grigoriev, Dick Jaarsma, Lukas C Kapitein, Anna Akhmanova, Casper C Hoogenraad
Polarized cargo transport is essential for neuronal function. However, the minimal basic components required for selective cargo sorting and distribution in neurons remain elusive. We found that in sensory neurons the axon initial segment is largely absent and that microtubule-associated protein 2 (MAP2) defines the cargo-filtering zone in the proximal axon. Here, MAP2 directs axonal cargo entry by coordinating the activities of molecular motors. We show that distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28424590/geometrical-determinants-of-neuronal-actin-waves
#5
Caterina Tomba, Céline Braïni, Ghislain Bugnicourt, Floriane Cohen, Benjamin M Friedrich, Nir S Gov, Catherine Villard
Hippocampal neurons produce in their early stages of growth propagative, actin-rich dynamical structures called actin waves. The directional motion of actin waves from the soma to the tip of neuronal extensions has been associated with net forward growth, and ultimately with the specification of neurites into axon and dendrites. Here, geometrical cues are used to control actin wave dynamics by constraining neurons on adhesive stripes of various widths. A key observable, the average time between the production of consecutive actin waves, or mean inter-wave interval (IWI), was identified...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28411148/behavioural-characterization-of-ankyring-deficient-mice-a-model-for-ank3-related-disorders
#6
I M van der Werf, D Van Dam, S Missault, B Yalcin, P P De Deyn, G Vandeweyer, R F Kooy
ANK3 encodes AnkyrinG (AnkG), a member of the Ankyrin family that is expressed in several different isoforms in many tissues. A unique serine-rich domain and tail domain in the two largest isoforms of AnkG (270 and 480kDa), restrict AnkG to the axon initial segment and nodes of Ranvier of myelinated neurons. At these sites, AnkG is a master regulator, coordinating the strict clustering of components necessary for proper action potential initiation and propagation along the axon. These components include voltage-gated sodium channels, potassium channels and members of the L1 cell adhesion molecule family...
April 11, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28331203/the-role-of-axonal-kv1-channels-in-ca3-pyramidal-cell-excitability
#7
Sylvain Rama, Mickael Zbili, Aurélie Fékété, Mónica Tapia, Maria José Benitez, Norah Boumedine, Juan José Garrido, Dominique Debanne
Axonal ion channels control spike initiation and propagation along the axon and determine action potential waveform. We show here that functional suppression of axonal Kv1 channels with local puff of dendrotoxin (DTx), laser or mechanical axotomy significantly increased excitability measured in the cell body. Importantly, the functional effect of DTx puffing or axotomy was not limited to the axon initial segment but was also seen on axon collaterals. In contrast, no effects were observed when DTx was puffed on single apical dendrites or after single dendrotomy...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331094/herpes-simplex-virus-ge-gi-and-us9-promote-both-envelopment-and-sorting-of-virus-particles-in-the-cytoplasm-of-neurons-two-processes-that-precede-anterograde-transport-in-axons
#8
Grayson DuRaine, Todd W Wisner, Paul Howard, David C Johnson
Herpes simplex virus (HSV) anterograde transport in neuronal axons is vital, allowing spread from latently-infected ganglia to epithelial tissues where viral progeny are produced in numbers allowing spread to other hosts. HSV membrane proteins gE/gI and US9 initiate the process of anterograde axonal transport ensuring that virus particles are transported from the cytoplasm into the most proximal segments of axons. These proteins do not appear to be important once HSV is inside axons. Previously we described HSV double mutants lacking both gE and US9 that failed to transport virus particles into axons...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28289377/loss-of-saltation-and-presynaptic-action-potential-failure-in-demyelinated-axons
#9
Mustafa S Hamada, Marko A Popovic, Maarten H P Kole
In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28284900/crosstalk-between-glia-extracellular-matrix-and-neurons
#10
REVIEW
Inseon Song, Alexander Dityatev
Extracellular matrix (ECM) molecules in the central nervous system form highly organized ECM structures around cell somata, axon initial segments, and synapses and play prominent roles in early development by guiding cell migration, neurite outgrowth and synaptogenesis, and by regulating closure of the critical period of development, synaptic plasticity and stability, cognitive flexibility, and axonal regeneration in adults. Major components of neural ECM, including chondroitin sulfate proteoglycans (CSPGs), tenascin-R and hyaluronic acid, are synthesized by both neurons and glial cells...
March 8, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28283581/mtcl1-plays-an-essential-role-in-maintaining-purkinje-neuron-axon-initial-segment
#11
Tomoko Satake, Kazunari Yamashita, Kenji Hayashi, Satoko Miyatake, Miwa Tamura-Nakano, Hiroshi Doi, Yasuhide Furuta, Go Shioi, Eriko Miura, Yukari H Takeo, Kunihiro Yoshida, Hiroyuki Yahikozawa, Naomichi Matsumoto, Michisuke Yuzaki, Atsushi Suzuki
The axon initial segment (AIS) is a specialized domain essential for neuronal function, the formation of which begins with localization of an ankyrin-G (AnkG) scaffold. However, the mechanism directing and maintaining AnkG localization is largely unknown. In this study, we demonstrate that in vivo knockdown of microtubule cross-linking factor 1 (MTCL1) in cerebellar Purkinje cells causes loss of axonal polarity coupled with AnkG mislocalization. MTCL1 lacking MT-stabilizing activity failed to restore these defects, and stable MT bundles spanning the AIS were disorganized in knockdown cells...
March 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28283543/kcnq-smit-complex-formation-facilitates-ion-channel-solute-transporter-cross-talk
#12
Daniel L Neverisky, Geoffrey W Abbott
Voltage-gated potassium channels formed by KCNQ2 and KCNQ3 are essential for normal neuronal excitability. KCNQ2/3 channel activity is augmented in vivo by phosphatidylinositol 4,5-bisphosphate (PIP2), which is generated from myo-inositol, an osmolyte transported into cells by sodium-dependent myo-inositol transporters (SMITs). Here, we discovered that KCNQ2/3 channels isoform-specifically colocalize with SMIT1 and SMIT2 at sciatic nerve nodes of Ranvier and in axon initial segments, and form channel-transporter complexes in vitro and in vivo KCNQ2/3 coexpression protected SMIT1 activity from the otherwise inhibitory effects of cellular depolarization imposed by elevating extracellular [K(+)], and KCNQ2 was required for potentiation of SMIT activity by myo-inositol preincubation...
March 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28269490/a-computational-model-of-orientation-dependent-activation-of-retinal-ganglion-cells
#13
Timothy Esler, Anthony N Burkitt, David B Grayden, Robert R Kerr, Bahman Tahayori, Hamish Meffin
Currently, a challenge in electrical stimulation for epiretinal prostheses is the avoidance of stimulation of axons of passage in the nerve fiber layer that originate from distant regions of the ganglion cell layer. A computational model of extracellular stimulation that captures the effect of neurite orientation in anisotropic tissue is developed using a modified version of the standard volume conductor model, known as the cellular composite model, embedded in a four layer model of the retina. Simulations are conducted to investigate the interaction of neural tissue orientation, electrode placement, and stimulation pulse duration and amplitude...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28235725/the-generator-site-in-acquired-autoimmune-neuromyotonia
#14
Miguel Oliveira Santos, Michael Swash, Mamede de Carvalho
OBJECTIVE: To investigate the origin of ectopic activity in neuromyotonia (NMT). METHODS: We studied two patients. In addition to routine studies, we tested synchronicity of spontaneous discharges in different motor units in simultaneous recordings made with two needle electrodes in the first dorsal interosseus muscle. Time-locked fasciculations in these double recordings would represent abnormal ectopic activity initiated in a nerve trunk with ephaptic stimulation of a nearby axon...
April 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/28227742/a-computational-model-of-orientation-dependent-activation-of-retinal-ganglion-cells
#15
Timothy Esler, Anthony N Burkitt, David B Grayden, Robert R Kerr, Bahman Tahayori, Hamish Meffin, Timothy Esler, Anthony N Burkitt, David B Grayden, Robert R Kerr, Bahman Tahayori, Hamish Meffin, Anthony N Burkitt, Timothy Esler, Hamish Meffin, David B Grayden, Robert R Kerr, Bahman Tahayori
Currently, a challenge in electrical stimulation for epiretinal prostheses is the avoidance of stimulation of axons of passage in the nerve fiber layer that originate from distant regions of the ganglion cell layer. A computational model of extracellular stimulation that captures the effect of neurite orientation in anisotropic tissue is developed using a modified version of the standard volume conductor model, known as the cellular composite model, embedded in a four layer model of the retina. Simulations are conducted to investigate the interaction of neural tissue orientation, electrode placement, and stimulation pulse duration and amplitude...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28184187/ankyrin-g-membrane-partners-drive-the-establishment-and-maintenance-of-the-axon-initial-segment
#16
Christophe Leterrier, Nadine Clerc, Fanny Rueda-Boroni, Audrey Montersino, Bénédicte Dargent, Francis Castets
The axon initial segment (AIS) is a highly specialized neuronal compartment that plays a key role in neuronal development and excitability. It concentrates multiple membrane proteins such as ion channels and cell adhesion molecules (CAMs) that are recruited to the AIS by the scaffold protein ankyrin G (ankG). The crucial function of ankG in the anchoring of AIS membrane components is well established, but a reciprocal role of membrane partners in ankG targeting and stabilization remained elusive. In rat cultured hippocampal neurons and cortical organotypic slices, we found that shRNA-mediated knockdown of ankG membrane partners (voltage-gated sodium channels (Nav) or neurofascin-186) led to a decrease of ankG concentration and perturbed the AIS formation and maintenance...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28181483/nf-%C3%AE%C2%BAb-regulates-neuronal-ankyrin-g-via-a-negative-feedback-loop
#17
Hans-Georg König, Robert Schwamborn, Silke Andresen, Sinéad Kinsella, Orla Watters, Beau Fenner, Jochen H M Prehn
The axon initial segment (AIS) is a neuronal compartment defined by ankyrin-G expression. We here demonstrate that the IKK-complex co-localizes and interacts with the cytoskeletal anchor protein ankyrin-G in immunoprecipitation and proximity-ligation experiments in cortical neurons. Overexpression of the 270 kDa variant of ankyrin-G suppressed, while gene-silencing of ankyrin-G expression increased nuclear factor-κB (NF-κB) activity in primary neurons, suggesting that ankyrin-G sequesters the transcription factor in the AIS...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179879/cannabinoid-receptors-modulate-neuronal-morphology-and-ankyring-density-at-the-axon-initial-segment
#18
Mónica Tapia, Ana Dominguez, Wei Zhang, Ana Del Puerto, María Ciorraga, María José Benitez, Carmen Guaza, Juan José Garrido
Neuronal polarization underlies the ability of neurons to integrate and transmit information. This process begins early in development with axon outgrowth, followed by dendritic growth and subsequent maturation. In between these two steps, the axon initial segment (AIS), a subcellular domain crucial for generating action potentials (APs) and maintaining the morphological and functional polarization, starts to develop. However, the cellular/molecular mechanisms and receptors involved in AIS initial development and maturation are mostly unknown...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28139716/adaptor-protein-2-ap-2-complex-is-essential-for-functional-axogenesis-in-hippocampal-neurons
#19
Jae Won Kyung, In Ha Cho, Sukmook Lee, Woo Keun Song, Timothy A Ryan, Michael B Hoppa, Sung Hyun Kim
The complexity and diversity of a neural network requires regulated elongation and branching of axons, as well as the formation of synapses between neurons. In the present study we explore the role of AP-2, a key endocytic adaptor protein complex, in the development of rat hippocampal neurons. We found that the loss of AP-2 during the early stage of development resulted in impaired axon extension and failed maturation of the axon initial segment (AIS). Normally the AIS performs two tasks in concert, stabilizing neural polarity and generating action potentials...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28119345/heparan-sulfates-support-pyramidal-cell-excitability-synaptic-plasticity-and-context-discrimination
#20
Daniel Minge, Oleg Senkov, Rahul Kaushik, Michel K Herde, Olga Tikhobrazova, Andreas B Wulff, Andrey Mironov, Toin H van Kuppevelt, Arie Oosterhof, Gaga Kochlamazashvili, Alexander Dityatev, Christian Henneberger
Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3-CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca2+ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons...
February 1, 2017: Cerebral Cortex
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