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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
#1
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
#2
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
#3
(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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28966641/reassembly-of-the-axon-initial-segment-and-nodes-of-ranvier-in-regenerated-axons-of-the-central-nervous-system
#11
Miguel A Marin, Matthew N Rasband
No abstract text is available yet for this article.
August 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28941293/cdk5-dependent-activation-of-dynein-in-the-axon-initial-segment-regulates-polarized-cargo-transport-in-neurons
#12
Eva Klinman, Mariko Tokito, Erika L F Holzbaur
The unique polarization of neurons depends on selective sorting of axonal and somatodendritic cargos to their correct compartments. Axodendritic sorting and filtering occurs within the axon initial segment (AIS). However, the underlying molecular mechanisms responsible for this filter are not well understood. Here, we show that local activation of the neuronal-specific kinase cyclin-dependent kinase 5 (CDK5) is required to maintain AIS integrity, as depletion or inhibition of CDK5 induces disordered microtubule polarity and loss of AIS cytoskeletal structure...
December 2017: Traffic
https://www.readbyqxmd.com/read/28935671/efa6-regulates-selective-polarised-transport-and-axon-regeneration-from-the-axon-initial-segment
#13
Richard Eva, Hiroaki Koseki, Venkateswarlu Kanamarlapudi, James W Fawcett
Central nervous system (CNS) axons lose their intrinsic ability to regenerate with maturity, whilst peripheral (PNS) axons do not. A key difference between these neuronal types is their ability to transport integrins into axons. Integrins can mediate PNS regeneration, but are excluded from adult CNS axons along with their rab11 carriers. We reasoned that exclusion of the contents of rab11 vesicles including integrins might contribute to the intrinsic inability of CNS neurons to regenerate, and investigated this using laser axotomy...
September 21, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28931427/serotonin-5-ht6-receptors-affect-cognition-in-a-mouse-model-of-alzheimer-s-disease-by-regulating-cilia-function
#14
Lili Hu, Bingjie Wang, Yan Zhang
BACKGROUND: Serotonin receptor 5-HT6 is involved in cognition and Alzheimer's disease (AD) development. However, the mechanism of 5-HT6 in AD pathology is not clear. METHODS: Since 5-HT6 is almost exclusively expressed in the primary cilia, using immunostaining we examined the number of cilia in the hippocampus of AD animal model APP/PS1 mice. By overexpressing and knocking down 5-HT6 in the primary cultured hippocampal neurons, we investigated the roles of 5-HT6 in alternating ciliary morphology...
September 20, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28922860/structural-plasticity-of-synaptopodin-in-the-axon-initial-segment-during-visual-cortex-development
#15
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
#16
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...
October 11, 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
#17
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
#18
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
#19
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 26, 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
#20
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
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