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axon initial segment

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https://www.readbyqxmd.com/read/28922860/structural-plasticity-of-synaptopodin-in-the-axon-initial-segment-during-visual-cortex-development
#1
Annabelle Schlüter, Domenico Del Turco, Thomas Deller, Annika Gutzmann, Christian Schultz, Maren Engelhardt
The axon initial segment (AIS) is essential for action potential generation. Recently, the AIS was identified as a site of neuronal plasticity. A subpopulation of AIS in cortical principal neurons contains stacks of endoplasmic reticulum (ER) forming the cisternal organelle (CO). The function of this organelle is poorly understood, but roles in local Ca2+-trafficking and AIS plasticity are discussed. To investigate whether the presence and/or the size of COs are linked to the development and maturation of AIS of cortical neurons, we analyzed the relationship between COs and the AIS during visual cortex development under control and visual deprivation conditions...
September 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28912162/regional-cellular-environment-shapes-phenotypic-variations-of-hippocampal-and-neocortical-chandelier-cells
#2
Yugo Ishino, Michael J Yetman, Serena M Sossi, André Steinecke, Yasufumi Hayano, Hiroki Taniguchi
Different cortical regions processing distinct information, such as the hippocampus and the neocortex, share common cellular components and circuit motifs but form unique networks by modifying these cardinal units. Cortical circuits include diverse types of GABAergic interneurons (INs) that shape activity of excitatory principal neurons (PNs). Canonical IN types conserved across distinct cortical regions have been defined by their morphological, electrophysiological, and neurochemical properties. However, it remains largely unknown whether canonical IN types undergo specific modifications in distinct cortical regions and display "regional variants"...
September 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28904989/antibodies-to-trim46-are-associated-with-paraneoplastic-neurological-syndromes
#3
Marleen H van Coevorden-Hameete, Sam F B van Beuningen, Matthieu Perrenoud, Lena M Will, Esther Hulsenboom, Jean-Francois Demonet, Lidia Sabater, Johan M Kros, Jan J G M Verschuuren, Maarten J Titulaer, Esther de Graaff, Peter A E Sillevis Smitt, Casper C Hoogenraad
Paraneoplastic neurological syndromes (PNS) are often characterized by the presence of antineuronal antibodies in patient serum or cerebrospinal fluid. The detection of antineuronal antibodies has proven to be a useful tool in PNS diagnosis and the search for an underlying tumor. Here, we describe three patients with autoantibodies to several epitopes of the axon initial segment protein tripartite motif 46 (TRIM46). We show that anti-TRIM46 antibodies are easy to detect in routine immunohistochemistry screening and can be confirmed by western blotting and cell-based assay...
September 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28894417/myosin-v-induces-cargo-immobilization-and-clustering-at-the-axon-initial-segment
#4
Anne F J Janssen, Roderick P Tas, Petra van Bergeijk, Rosalie Oost, Casper C Hoogenraad, Lukas C Kapitein
The selective transport of different cargoes into axons and dendrites underlies the polarized organization of the neuron. Although it has become clear that the combined activity of different motors determines the destination and selectivity of transport, little is known about the mechanistic details of motor cooperation. For example, the exact role of myosin-V in opposing microtubule-based axon entries has remained unclear. Here we use two orthogonal chemically-induced heterodimerization systems to independently recruit different motors to cargoes...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28894008/genetic-disruption-of-ankyrin-g-in-adult-mouse-forebrain-causes-cortical-synapse-alteration-and-behavior-reminiscent-of-bipolar-disorder
#5
Shanshan Zhu, Zachary A Cordner, Jiali Xiong, Chi-Tso Chiu, Arabiye Artola, Yanning Zuo, Andrew D Nelson, Tae-Yeon Kim, Natalya Zaika, Brian M Woolums, Evan J Hess, Xiaofang Wang, De-Maw Chuang, Mikhail M Pletnikov, Paul M Jenkins, Kellie L Tamashiro, Christopher A Ross
Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS). We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28882300/synchrotron-small-angle-x-ray-scattering-and-electron-microscopy-characterization-of-structures-and-forces-in-microtubule-tau-mixtures
#6
Peter J Chung, Chaeyeon Song, Herbert P Miller, Youli Li, Uri Raviv, Myung Chul Choi, Leslie Wilson, Stuart C Feinstein, Cyrus R Safinya
Tau, a neuronal protein known to bind to microtubules and thereby regulate microtubule dynamic instability, has been shown recently to not only undergo conformational transitions on the microtubule surface as a function of increasing microtubule coverage density (i.e., with increasing molar ratio of Tau to tubulin dimers) but also to mediate higher-order microtubule architectures, mimicking fascicles of microtubules found in the axon initial segment. These discoveries would not have been possible without fine structure characterization of microtubules, with and without applied osmotic pressure through the use of depletants...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28861035/molecular-disorganization-of-axons-adjacent-to-human-cortical-microinfarcts
#7
Hamza Coban, Spencer Tung, Bryan Yoo, Harry V Vinters, Jason D Hinman
Cortical microinfarcts (CMIs) are microscopically identified wedge-shaped ischemic lesions that occur at or near the cortical surface and result from occlusion of penetrating arterioles. These microscopic lesions can be observed with high-resolution magnetic resonance imaging in aging brains and in patients with cerebrovascular disease. Recent studies have suggested that strategically located microinfarcts strongly correlate with cognitive deficits, which can contribute to Alzheimer's disease as well as other forms of dementia...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28855741/the-impact-of-cytoskeletal-organization-on-the-local-regulation-of-neuronal-transport
#8
REVIEW
Jeffrey J Nirschl, Amy E Ghiretti, Erika L F Holzbaur
Neurons are akin to modern cities in that both are dependent on robust transport mechanisms. Like the best mass transit systems, trafficking in neurons must be tailored to respond to local requirements. Neurons depend on both high-speed, long-distance transport and localized dynamics to correctly deliver cargoes and to tune synaptic responses. Here, we focus on the mechanisms that provide localized regulation of the transport machinery, including the cytoskeleton and molecular motors, to yield compartment-specific trafficking in the axon initial segment, axon terminal, dendrites and spines...
October 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28828584/neurons-with-multiple-axons-have-functional-axon-initial-segments
#9
Yu Guo, Zhuo Liu, Yi-Kun Chen, Zhen Chai, Chen Zhou, Yan Zhang
Neurons grow multiple axons after treatment with glycogen synthase kinase-3 (GSK-3) inhibitors. However, whether they are electrically active is not known. Here, we examined the role of multiple axons as electrophysiological components during neuronal firing. Combining pharmacological, immunofluorescence, and electrophysiological methods, we found that more neurons had multiple axon initial segments (AISs) after inhibition of GSK-3 activity with SB415286. The multiple AISs induced by GSK-3 inhibition were enriched with voltage-gated sodium channels...
August 21, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28822872/different-mossy-fiber-sprouting-patterns-in-ilae-hippocampal-sclerosis-types
#10
Barbara Schmeiser, Jinmei Li, Armin Brandt, Josef Zentner, Soroush Doostkam, Thomas M Freiman
OBJECTIVE: Hippocampal sclerosis (HS) is the most prevalent pathology in temporal lobe epilepsy (TLE) characterized by segmental neuronal cell loss in the cornu ammonis (CA) 1-4. In addition, migration of granule cells and reorganization of their axons is observed, known as granule cell dispersion (GCD) and mossy fiber sprouting (MFS). The loss of mossy fibers` (MF) target cells in CA4 and CA3 was considered to be causative for MFS. The ILAE HS (International League Against Epilepsy) classification identifies three subtypes with different cell loss patterns in CA1-4...
August 8, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28795433/schwann-cell-dedifferentiation-associated-demyelination-leads-to-exocytotic-myelin-clearance-in-inflammatory-segmental-demyelination
#11
So Young Jang, Byeol-A Yoon, Yoon Kyung Shin, Seoug Hoon Yun, Young Rae Jo, Yun Young Choi, Meejung Ahn, Taekyun Shin, Joo In Park, Jong Kuk Kim, Hwan Tae Park
Schwann cells (SCs), which form the peripheral myelin sheath, have the unique ability to dedifferentiate and to destroy the myelin sheath under various demyelination conditions. During SC dedifferentiation-associated demyelination (SAD) in Wallerian degeneration (WD) after axonal injury, SCs exhibit myelin and junctional instability, down-regulation of myelin gene expression and autophagic myelin breakdown. However, in inflammatory demyelinating neuropathy (IDN), it is still unclear how SCs react and contribute to segmental demyelination before myelin scavengers, macrophages, are activated for phagocytotic myelin digestion...
August 10, 2017: Glia
https://www.readbyqxmd.com/read/28739523/activity-dependent-axonal-plasticity-in-sensory-systems
#12
REVIEW
Nora Jamann, Merryn Jordan, Maren Engelhardt
The rodent whisker-to-barrel cortex pathway is a classic model to study the effects of sensory experience and deprivation on neuronal circuit formation, not only during development but also in the adult. Decades of research have produced a vast body of evidence highlighting the fundamental role of neuronal activity (spontaneous and/or sensory-evoked) for circuit formation and function. In this context, it has become clear that neuronal adaptation and plasticity is not just a function of the neonatal brain, but persists into adulthood, especially after experience-driven modulation of network status...
July 21, 2017: Neuroscience
https://www.readbyqxmd.com/read/28734032/characterization-of-the-axon-initial-segment-of-mice-substantia-nigra-dopaminergic-neurons
#13
Cristian González-Cabrera, Rodrigo Meza, Lorena Ulloa, Paulina Merino-Sepúlveda, Valentina Luco, Ana Sanhueza, Alejandro Oñate-Ponce, J Paul Bolam, Pablo Henny
The axon initial segment (AIS) is the site of initiation of action potentials and influences action potential waveform, firing pattern, and rate. In view of the fundamental aspects of motor function and behavior that depend on the firing of substantia nigra pars compacta (SNc) dopaminergic neurons, we identified and characterized their AIS in the mouse. Immunostaining for tyrosine hydroxylase (TH), sodium channels (Nav ) and ankyrin-G (Ank-G) was used to visualize the AIS of dopaminergic neurons. Reconstructions of sampled AIS of dopaminergic neurons revealed variable lengths (12-60 μm) and diameters (0...
July 22, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28713955/altered-axon-initial-segment-in-hippocampal-newborn-neurons-associated-with-recurrence-of-temporal-lobe-epilepsy-in-rats
#14
Tian-Tian Liu, Li Feng, Heng-Fang Liu, Yi Shu, Bo Xiao
Hippocampal neurogenesis in temporal lobe epilepsy (TLE) may result in alteration of the excitability of neurons, which contributes to spontaneous recurrent seizures. Axon initial segment (AIS) structural and functional plasticity is important in the control of neuronal excitability. It remains to be elucidated whether the plasticity of AIS occurs in hippocampal newly‑generated neurons that are involved in recurrent seizures following pilocarpine‑induced status epilepticus (SE). The present study first established a pilocarpine‑induced TLE rat model to assess the features of newborn neurons and AIS plasticity alterations using double immunofluorescence staining of Ankyrin G and doublecortin (DCX)...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28709993/intracellular-calcium-release-through-ip3r-or-ryr-contributes-to-secondary-axonal-degeneration
#15
Ben C Orem, Nicolas Pelisch, Joshua Williams, Jacqueline M Nally, David P Stirling
Severed CNS axons often retract or dieback away from the injury site and fail to regenerate. The precise mechanisms underlying acute axonal dieback and secondary axonal degeneration remain poorly understood. Here we investigate the role of Ca(2+) store mediated intra-axonal Ca(2+) release in acute axonal dieback and secondary axonal degeneration. To differentiate between primary (directly transected) and "bystander" axonal injury (axons spared by the initial injury but then succumb to secondary degeneration) in real-time we use our previously published highly focal laser-induced spinal cord injury (LiSCI) ex vivo model...
July 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28683314/periadolescent-maturation-of-gabaergic-hyperpolarization-at-the-axon-initial-segment
#16
Gina Rinetti-Vargas, Khanhky Phamluong, Dorit Ron, Kevin J Bender
Neuronal chloride levels are developmentally regulated. Early in life, high intracellular concentrations support chloride efflux and depolarization at GABAergic synapses. In mouse, intracellular chloride decreases over the first postnatal week in the somatodendritic compartment, eventually supporting mature, hyperpolarizing GABAergic inhibition. In contrast to this dendritic switch, it is less clear how GABAergic signaling at the axon initial segment (AIS) functions in mature pyramidal cells, as reports of both depolarization and hyperpolarization have been reported in the AIS past the first postnatal week...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28673977/lgi1-tunes-intrinsic-excitability-by-regulating-the-density-of-axonal-kv1-channels
#17
Michael Seagar, Michael Russier, Olivier Caillard, Yves Maulet, Laure Fronzaroli-Molinieres, Marina De San Feliciano, Norah Boumedine-Guignon, Léa Rodriguez, Mickael Zbili, Fabrice Usseglio, Christine Formisano-Tréziny, Fahamoe Youssouf, Marion Sangiardi, Morgane Boillot, Stéphanie Baulac, María José Benitez, Juan-José Garrido, Dominique Debanne, Oussama El Far
Autosomal dominant epilepsy with auditory features results from mutations in leucine-rich glioma-inactivated 1 (LGI1), a soluble glycoprotein secreted by neurons. Animal models of LGI1 depletion display spontaneous seizures, however, the function of LGI1 and the mechanisms by which deficiency leads to epilepsy are unknown. We investigated the effects of pure recombinant LGI1 and genetic depletion on intrinsic excitability, in the absence of synaptic input, in hippocampal CA3 neurons, a classical focus for epileptogenesis...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28643105/differential-role-of-gabaa-receptors-and-neuroligin-2-for-perisomatic-gabaergic-synapse-formation-in-the-hippocampus
#18
Patrizia Panzanelli, Simon Früh, Jean-Marc Fritschy
Perisomatic GABAergic synapses onto hippocampal pyramidal cells arise from two populations of basket cells with different neurochemical and functional properties. The presence of the dystrophin-glycoprotein complex in their postsynaptic density (PSD) distinguishes perisomatic synapses from GABAergic synapses on dendrites and the axon-initial segment. Targeted deletion of neuroligin 2 (NL2), a transmembrane protein interacting with presynaptic neurexin, has been reported to disrupt postsynaptic clustering of GABAA receptors (GABAAR) and their anchoring protein, gephyrin, at perisomatic synapses...
June 22, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28634442/mild-traumatic-brain-injury-evokes-pyramidal-neuron-axon-initial-segment-plasticity-and-diffuse-presynaptic-inhibitory-terminal-loss
#19
Michal Vascak, Jianli Sun, Matthew Baer, Kimberle M Jacobs, John T Povlishock
The axon initial segment (AIS) is the site of action potential (AP) initiation, thus a crucial regulator of neuronal activity. In excitatory pyramidal neurons, the high density of voltage-gated sodium channels (NaV1.6) at the distal AIS regulates AP initiation. A surrogate AIS marker, ankyrin-G (ankG) is a structural protein regulating neuronal functional via clustering voltage-gated ion channels. In neuronal circuits, changes in presynaptic input can alter postsynaptic output via AIS structural-functional plasticity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28624616/age-related-plasticity-of-the-axon-initial-segment-of-cortical-pyramidal-cells-in-marmoset-monkeys
#20
Nafiseh Atapour, Marcello G P Rosa
Structural plasticity of the axon initial segment (AIS), the site of action potential initiation, is observed as part of the normal early development of the cortex, as well as in association with injury and disease. Here, we show that structural AIS plasticity also occurs with normal aging in adult marmosets. Immunohistochemical techniques were used to reveal the extent of the AIS of layer 2/3A pyramidal cells in 8 neocortical areas. We found that the AIS length varied significantly between areas in young adult (2-3 years old) marmosets, with neurons in frontal area 14C having the longest AIS, and those in the primary visual cortex the shortest...
September 2017: Neurobiology of Aging
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