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https://www.readbyqxmd.com/read/28091722/hyperphosphorylated-tau-causes-reduced-hippocampal-ca1-excitability-by-relocating-the-axon-initial-segment
#1
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
#2
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
#3
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-multi-partner-ankyrin-and-spectrin-binding-protein-involved-in-the-organization-of-nodes-of-ranvier
#4
Pierre-Marie Martin, Carmen Cifuentes-Diaz, Jérôme Devaux, Marta Garcia, Jocelyne Bureau, Sylvie Thomasseau, Esther Klingler, Jean-Antoine Girault, Laurence Goutebroze
Nodes of Ranvier are essential regions for action potential conduction in myelinated fibers. They are enriched in multimolecular complexes comprised 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...
December 15, 2016: 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
#5
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
#6
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
https://www.readbyqxmd.com/read/27932952/evaluating-tools-for-live-imaging-of-structural-plasticity-at-the-axon-initial-segment
#7
Adna S Dumitrescu, Mark D Evans, Matthew S Grubb
The axon initial segment (AIS) is a specialized neuronal compartment involved in the maintenance of axo-dendritic polarity and in the generation of action potentials. It is also a site of significant structural plasticity-manipulations of neuronal activity in vitro and in vivo can produce changes in AIS position and/or size that are associated with alterations in intrinsic excitability. However, to date all activity-dependent AIS changes have been observed in experiments carried out on fixed samples, offering only a snapshot, population-wide view of this form of plasticity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27930291/covariation-of-axon-initial-segment-location-and-dendritic-tree-normalizes-the-somatic-action-potential
#8
Mustafa S Hamada, Sarah Goethals, Sharon I de Vries, Romain Brette, Maarten H P Kole
In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911898/bilaterian-giant-ankyrins-have-a-common-evolutionary-origin-and-play-a-conserved-role-in-patterning-the-axon-initial-segment
#9
Timothy Jegla, Michelle M Nguyen, Chengye Feng, Daniel J Goetschius, Esteban Luna, Damian B van Rossum, Bishoy Kamel, Aditya Pisupati, Elliott S Milner, Melissa M Rolls
In vertebrate neurons, the axon initial segment (AIS) is specialized for action potential initiation. It is organized by a giant 480 Kd variant of ankyrin G (AnkG) that serves as an anchor for ion channels and is required for a plasma membrane diffusion barrier that excludes somatodendritic proteins from the axon. An unusually long exon required to encode this 480Kd variant is thought to have been inserted only recently during vertebrate evolution, so the giant ankyrin-based AIS scaffold has been viewed as a vertebrate adaptation for fast, precise signaling...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27884423/alterations-in-a-unique-class-of-cortical-chandelier-cell-axon-cartridges-in-schizophrenia
#10
Brad R Rocco, Adam M DeDionisio, David A Lewis, Kenneth N Fish
BACKGROUND: The axons of chandelier cells (ChCs) target the axon initial segment of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of axon initial segments detectable by immunoreactivity for the α2 subunit of the GABAA receptor is higher in layers 2/superficial 3 of the prefrontal cortex. These findings were interpreted as compensatory responses to lower GABA levels in ChCs...
September 29, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27881784/low-somatic-sodium-conductance-enhances-action-potential-precision-in-time-coding-auditory-neurons
#11
Yang Yang, Bina Ramamurthy, Andreas Neef, Matthew A Xu-Friedman
: Auditory nerve fibers encode sounds in the precise timing of action potentials (APs), which is used for such computations as sound localization. Timing information is relayed through several cell types in the auditory brainstem that share an unusual property: their APs are not overshooting, suggesting that the cells have very low somatic sodium conductance (gNa). However, it is not clear how gNa influences temporal precision. We addressed this by comparing bushy cells (BCs) in the mouse cochlear nucleus with T-stellate cells (SCs), which do have normal overshooting APs...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27871891/long-term-alcohol-exposure-elicits-hippocampal-nonsynaptic-epileptiform-activity-changes-associated-with-expression-and-functional-changes-in-nkcc1-kcc2-co-transporters-and-na-k-atpase
#12
Luiz E C Santos, Antônio M Rodrigues, Mariana R Lopes, Victor D C Costa, Carla A Scorza, Fulvio A Scorza, Esper A Cavalheiro, Antônio-Carlos G Almeida
Nonsynaptic mechanism changes, particularly the enhancement of NKCC1 expression in the dentate gyrus (DG) after 4weeks of ethanol consumption, motivate the present work, in which rats were submitted to a period of chronic consumption (12weeks). Four groups of six animals (6-week-old male Wistar rats) were formed, including the control (C), ethanol 1 (E1), ethanol 2 (E2) and ethanol 3 (E3) groups. The rats in the E1, E2 and E3 groups were treated daily with a 30% v/v solution of ethanol, administered via oral gavage (1...
January 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27861786/infantile-spasms-and-encephalopathy-without-preceding-neonatal-seizures-caused-by-kcnq2-r198q-a-gain-of-function-variant
#13
John J Millichap, Francesco Miceli, Michela De Maria, Cynthia Keator, Nishtha Joshi, Baouyen Tran, Maria Virginia Soldovieri, Paolo Ambrosino, Vandana Shashi, Mohamad A Mikati, Edward C Cooper, Maurizio Taglialatela
Variants in KCNQ2 encoding for Kv 7.2 neuronal K(+) channel subunits lead to a spectrum of neonatal-onset epilepsies, ranging from self-limiting forms to severe epileptic encephalopathy. Most KCNQ2 pathogenic variants cause loss-of-function, whereas few increase channel activity (gain-of-function). We herein provide evidence for a new phenotypic and functional profile in KCNQ2-related epilepsy: infantile spasms without prior neonatal seizures associated with a gain-of-function gene variant. With use of an international registry, we identified four unrelated patients with the same de novo heterozygous KCNQ2 c...
January 2017: Epilepsia
https://www.readbyqxmd.com/read/27859267/human-motoneurone-excitability-is-depressed-by-activation-of-serotonin-1a-receptors-with-buspirone
#14
Jessica M D'Amico, Annie A Butler, Martin E Héroux, Florence Cotel, Jean-François M Perrier, Jane E Butler, Simon C Gandevia, Janet L Taylor
KEY POINTS: In the adult turtle spinal cord, action potential generation in motoneurones is inhibited by spillover of serotonin to extrasynaptic serotonin 1A (5-HT1A ) receptors at the axon initial segment. We explored whether ingestion of the 5-HT1A receptor partial agonist, buspirone, decreases motoneurone excitability in humans. Following ingestion of buspirone, two tests of motoneurone excitability showed decreases. F-wave areas and persistence in an intrinsic muscle of the hand were reduced, as was the area of cervicomedullary motor evoked potentials in biceps brachii...
November 17, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27852734/increases-in-human-motoneuron-excitability-after-cervical-spinal-cord-injury-depend-on-the-level-of-injury
#15
Christine K Thomas, Charlotte K Hager, Cliff S Klein
After human spinal cord injury (SCI), motoneuron recruitment and firing rate during voluntary and involuntary contractions may be altered by changes in motoneuron excitability. Our aim was to compare F-waves in single thenar motor units paralyzed by cervical SCI to those in uninjured controls because at the single unit level, F-waves primarily reflect the intrinsic properties of the motoneuron and its initial segment. With intraneural motor axon stimulation, F-waves were evident in all four participants with C4-level SCI, absent in eight with C5 or C6 injury, and present in six of 12 Uninjured participants (p<0...
November 16, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27834648/epidural-stimulation-of-rat-spinal-cord-at-lumbosacral-segment-using-a-surface-electrode-a-computer-simulation-study
#16
Qi Xu, Li Kong, Hui Zhou, Jiping He
Clinical research indicates that the epidural spinal cord stimulation (ESCS) at lumbosacral segment has shown potential for promoting locomotor recovery in patients with incomplete spinal cord injury. However, the underlying neural mechanism needs to be determined by animal experiments. In order to refine experimental protocols, we used a finite element simulation to investigate the activation of nerve fibers in a rat spinal cord model. Our model is composed of a volume conductor model from L1 to S2 spinal segments and the McIntyre-Richard-Grill axon model, which is used to investigate the threshold of selected spinal fibers with different diameters at varied locations and predict the neural responses of any target fibers with bipolar electrode configuration...
November 4, 2016: IEEE Transactions on Neural Systems and Rehabilitation Engineering
https://www.readbyqxmd.com/read/27826229/structural-and-functional-plasticity-at-the-axon-initial-segment
#17
REVIEW
Rei Yamada, Hiroshi Kuba
The axon initial segment (AIS) is positioned between the axonal and somato-dendritic compartments and plays a pivotal role in triggering action potentials (APs) and determining neuronal output. It is now widely accepted that structural properties of the AIS, such as length and/or location relative to the soma, change in an activity-dependent manner. This structural plasticity of the AIS is known to be crucial for homeostatic control of neuronal excitability. However, it is obvious that the impact of the AIS on neuronal excitability is critically dependent on the biophysical properties of the AIS, which are primarily determined by the composition and characteristics of ion channels in this domain...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27819336/phase-transitions-and-self-organized-criticality-in-networks-of-stochastic-spiking-neurons
#18
Ludmila Brochini, Ariadne de Andrade Costa, Miguel Abadi, Antônio C Roque, Jorge Stolfi, Osame Kinouchi
Phase transitions and critical behavior are crucial issues both in theoretical and experimental neuroscience. We report analytic and computational results about phase transitions and self-organized criticality (SOC) in networks with general stochastic neurons. The stochastic neuron has a firing probability given by a smooth monotonic function Φ(V) of the membrane potential V, rather than a sharp firing threshold. We find that such networks can operate in several dynamic regimes (phases) depending on the average synaptic weight and the shape of the firing function Φ...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27717670/formation-and-disruption-of-functional-domains-in-myelinated-cns-axons
#19
Ryan B Griggs, Leonid M Yermakov, Keiichiro Susuki
Communication in the central nervous system (CNS) occurs through initiation and propagation of action potentials at excitable domains along axons. Action potentials generated at the axon initial segment (AIS) are regenerated at nodes of Ranvier through the process of saltatory conduction. Proper formation and maintenance of the molecular structure at the AIS and nodes are required for sustaining conduction fidelity. In myelinated CNS axons, paranodal junctions between the axolemma and myelinating oligodendrocytes delineate nodes of Ranvier and regulate the distribution and localization of specialized functional elements, such as voltage-gated sodium channels and mitochondria...
October 4, 2016: Neuroscience Research
https://www.readbyqxmd.com/read/27697928/nanoscopic-compartmentalization-of-membrane-protein-motion-at-the-axon-initial-segment
#20
David Albrecht, Christian M Winterflood, Mohsen Sadeghi, Thomas Tschager, Frank Noé, Helge Ewers
The axon initial segment (AIS) is enriched in specific adaptor, cytoskeletal, and transmembrane molecules. During AIS establishment, a membrane diffusion barrier is formed between the axonal and somatodendritic domains. Recently, an axonal periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like structures has been discovered. However, whether this structure is related to the diffusion barrier function is unclear. Here, we performed single-particle tracking time-course experiments on hippocampal neurons during AIS development...
October 10, 2016: Journal of Cell Biology
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