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https://www.readbyqxmd.com/read/28331203/the-role-of-axonal-kv1-channels-in-ca3-pyramidal-cell-excitability
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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 Ca(2+) influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons...
January 23, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28091722/hyperphosphorylated-tau-causes-reduced-hippocampal-ca1-excitability-by-relocating-the-axon-initial-segment
#15
Robert John Hatch, Yan Wei, Di Xia, Jürgen Götz
Hyperphosphorylated tau has a critical role in tauopathies such as Alzheimer's disease and frontotemporal dementia, impairing neuronal function and eventually leading to neurodegeneration. A critical role for tau is supported by studies in transgenic mouse models that express the P301L tau mutation found in cases of familial frontotemporal dementia, with the accumulation of hyperphosphorylated tau in the hippocampus causing reductions in hippocampal long-term potentiation and impairments in spatial learning and memory...
January 16, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28068338/spikelets-in-pyramidal-neurons-action-potentials-initiated-in-the-axon-initial-segment-that-do-not-activate-the-soma
#16
Martina Michalikova, Michiel W H Remme, Richard Kempter
Spikelets are small spike-like depolarizations that can be measured in somatic intracellular recordings. Their origin in pyramidal neurons remains controversial. To explain spikelet generation, we propose a novel single-cell mechanism: somato-dendritic input generates action potentials at the axon initial segment that may fail to activate the soma and manifest as somatic spikelets. Using mathematical analysis and numerical simulations of compartmental neuron models, we identified four key factors controlling spikelet generation: (1) difference in firing threshold, (2) impedance mismatch, and (3) electrotonic separation between the soma and the axon initial segment, as well as (4) input amplitude...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/27994149/fgf14-is-a-regulator-of-kcnq2-3-channels
#17
Juan Lorenzo Pablo, Geoffrey S Pitt
KCNQ2/3 (Kv7.2/7.3) channels and voltage-gated sodium channels (VGSCs) are enriched in the axon initial segment (AIS) where they bind to ankyrin-G and coregulate membrane potential in central nervous system neurons. The molecular mechanisms supporting coordinated regulation of KCNQ and VGSCs and the cellular mechanisms governing KCNQ trafficking to the AIS are incompletely understood. Here, we show that fibroblast growth factor 14 (FGF14), previously described as a VGSC regulator, also affects KCNQ function and localization...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27979964/schwannomin-interacting-protein-1-isoform-iqcj-schip1-is-a-multipartner-ankyrin-and-spectrin-binding-protein-involved-in-the-organization-of-nodes-of-ranvier
#18
Pierre-Marie Martin, Carmen Cifuentes-Diaz, Jérôme Devaux, Marta Garcia, Jocelyne Bureau, Sylvie Thomasseau, Esther Klingler, Jean-Antoine Girault, Laurence Goutebroze
The nodes of Ranvier are essential regions for action potential conduction in myelinated fibers. They are enriched in multimolecular complexes composed of voltage-gated Nav and Kv7 channels associated with cell adhesion molecules. Cytoskeletal proteins ankyrin-G (AnkG) and βIV-spectrin control the organization of these complexes and provide mechanical support to the plasma membrane. IQCJ-SCHIP1 is a cytoplasmic protein present in axon initial segments and nodes of Ranvier. It interacts with AnkG and is absent from nodes and axon initial segments of βIV-spectrin and AnkG mutant mice...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27966487/expressions-of-visual-pigments-and-synaptic-proteins-in-neonatal-chick-retina-exposed-to-light-of-variable-photoperiods
#19
Kumar Abhiram Jha, Tapas C Nag, Shashi Wadhwa, Tara Sankar Roy
Light causes damage to the retina, which is one of the supposed factors for age-related macular degeneration in human. Some animal species show drastic retinal changes when exposed to intense light (e.g. albino rats). Although birds have a pigmented retina, few reports indicated its susceptibility to light damage. To know how light influences a cone-dominated retina (as is the case with human), we examined the effects of moderate light intensity on the retina of white Leghorn chicks (Gallus g. domesticus). The newly hatched chicks were initially acclimatized at 500 lux for 7 days in 12 h light: 12 h dark cycles (12L:12D)...
December 2016: Journal of Biosciences
https://www.readbyqxmd.com/read/27956739/ankyrin-g-isoform-imbalance-and-interneuronopathy-link-epilepsy-and-bipolar-disorder
#20
A Y Lopez, X Wang, M Xu, A Maheshwari, D Curry, S Lam, A M Adesina, J L Noebels, Q-Q Sun, E C Cooper
ANK3, encoding the adaptor protein Ankyrin-G (AnkG), has been implicated in bipolar disorder by genome-wide association studies. ANK3 has multiple alternative first exons, and a bipolar disorder-associated ANK3 variant has been shown to reduce the expression of exon 1b. Here we identify mechanisms through which reduced ANK3 exon 1b isoform expression disrupts neuronal excitation-inhibition balance. We find that parvalbumin (PV) interneurons and principal cells differentially express ANK3 first exon subtypes...
December 13, 2016: Molecular Psychiatry
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