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https://www.readbyqxmd.com/read/27884423/alterations-in-a-unique-class-of-cortical-chandelier-cell-axon-cartridges-in-schizophrenia
#1
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
#2
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
#3
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...
November 18, 2016: Neuroscience
https://www.readbyqxmd.com/read/27861786/infantile-spasms-and-encephalopathy-without-preceding-neonatal-seizures-caused-by-kcnq2-r198q-a-gain-of-function-variant
#4
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...
November 9, 2016: Epilepsia
https://www.readbyqxmd.com/read/27859267/human-motoneurone-excitability-is-depressed-by-activation-of-5ht1a-receptors-with-buspirone
#5
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
Intense serotonergic drive in the turtle spinal cord results in serotonin spillover to the axon initial segment of the motoneurones where it activates 5HT1A receptors and inhibits generation of action potentials. We examined whether activation of 5HT1A receptors decreases motoneurone excitability in humans by determining the effects of a 5HT1A receptor partial agonist, buspirone, on F waves and cervicomedullary motor evoked potentials (CMEPs). In a placebo-controlled double-blind study, 10 participants were tested on two occasions where either placebo or 20 mg buspirone was administered orally...
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27697921/organization-of-the-axon-initial-segment-actin-like-a-fence
#12
Yu-Mei Huang, Matthew N Rasband
What prevents the movement of membrane molecules between axonal and somatodendritic domains is unclear. In this issue, Albrecht et. al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201603108) demonstrate via high-speed single-particle tracking and superresolution microscopy that lipid-anchored molecules in the axon initial segment are confined to membrane domains separated by periodically spaced actin rings.
October 10, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27666389/fhf-independent-conduction-of-action-potentials-along-the-leak-resistant-cerebellar-granule-cell-axon
#13
Katarzyna Dover, Christopher Marra, Sergio Solinas, Marko Popovic, Sathyaa Subramaniyam, Dejan Zecevic, Egidio D'Angelo, Mitchell Goldfarb
Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell's unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Nav inactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials...
September 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27637565/homeostatic-plasticity-of-subcellular-neuronal-structures-from-inputs-to-outputs
#14
Winnie Wefelmeyer, Christopher J Puhl, Juan Burrone
Neurons in the brain are highly plastic, allowing an organism to learn and adapt to its environment. However, this ongoing plasticity is also inherently unstable, potentially leading to aberrant levels of circuit activity. Homeostatic forms of plasticity are thought to provide a means of controlling neuronal activity by avoiding extremes and allowing network stability. Recent work has shown that many of these homeostatic modifications change the structure of subcellular neuronal compartments, ranging from changes to synaptic inputs at both excitatory and inhibitory compartments to modulation of neuronal output through changes at the axon initial segment (AIS) and presynaptic terminals...
October 2016: Trends in Neurosciences
https://www.readbyqxmd.com/read/27634356/gabaergic-synapses-at-the-axon-initial-segment-of-basolateral-amygdala-projection-neurons-modulate-fear-extinction
#15
Rinki Saha, Stephanie Knapp, Darpan Chakraborty, Omer Horovitz, Anne Albrecht, Martin Kriebel, Hanoch Kaphzan, Ingrid Ehrlich, Hansjürgen Volkmer, Gal Richter-Levin
Inhibitory synaptic transmission in the amygdala plays a pivotal role in fear learning and its extinction. However, the local circuits formed by GABAergic inhibitory interneurons within the amygdala and their detailed function in shaping these behaviors are not well understood. Here, we employed lentiviral-mediated knockdown of the cell adhesion molecule neurofascin in the basolateral amygdala (BLA) to specifically remove inhibitory synapses at the axon initial segment (AIS) of BLA projection neurons. Quantitative analysis of GABAergic synapse markers and measurement of miniature inhibitory postsynaptic currents in BLA projection neurons after neurofascin knockdown ex vivo confirmed the loss of GABAergic input...
September 16, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27618676/dual-function-of-nrp1-in-axon-guidance-and-subcellular-target-recognition-in-cerebellum
#16
Ludovic Telley, Christelle Cadilhac, Jean-Michel Cioni, Veronique Saywell, Céline Jahannault-Talignani, Rosa E Huettl, Catherine Sarrailh-Faivre, Alexandre Dayer, Andrea B Huber, Fabrice Ango
Subcellular target recognition in the CNS is the culmination of a multiple-step program including axon guidance, target recognition, and synaptogenesis. In cerebellum, basket cells (BCs) innervate the soma and axon initial segment (AIS) of Purkinje cells (PCs) to form the pinceau synapse, but the underlying mechanisms remain incompletely understood. Here, we demonstrate that neuropilin-1 (NRP1), a Semaphorin receptor expressed in BCs, controls both axonal guidance and subcellular target recognition. We show that loss of Semaphorin 3A function or specific deletion of NRP1 in BCs alters the stereotyped organization of BC axon and impairs pinceau synapse formation...
September 21, 2016: Neuron
https://www.readbyqxmd.com/read/27586289/developmental-and-regulatory-functions-of-na-channel-non-pore-forming-%C3%AE-subunits
#17
J J Winters, L L Isom
Voltage-gated Na(+) channels (VGSCs) isolated from mammalian neurons are heterotrimeric complexes containing one pore-forming α subunit and two non-pore-forming β subunits. In excitable cells, VGSCs are responsible for the initiation of action potentials. VGSC β subunits are type I topology glycoproteins, containing an extracellular amino-terminal immunoglobulin (Ig) domain with homology to many neural cell adhesion molecules (CAMs), a single transmembrane segment, and an intracellular carboxyl-terminal domain...
2016: Current Topics in Membranes
https://www.readbyqxmd.com/read/27581456/reassembly-of-excitable-domains-after-cns-axon-regeneration
#18
Miguel A Marin, Silmara de Lima, Hui-Ya Gilbert, Roman J Giger, Larry Benowitz, Matthew N Rasband
UNLABELLED: Action potential initiation and propagation in myelinated axons require ion channel clustering at axon initial segments (AIS) and nodes of Ranvier. Disruption of these domains after injury impairs nervous system function. Traditionally, injured CNS axons are considered refractory to regeneration, but some recent approaches challenge this view by showing robust long-distance regeneration. However, whether these approaches allow remyelination and promote the reestablishment of AIS and nodes of Ranvier is unknown...
August 31, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27537197/similar-gabaa-receptor-subunit-composition-in-somatic-and-axon-initial-segment-synapses-of-hippocampal-pyramidal-cells
#19
Katalin Kerti-Szigeti, Zoltan Nusser
Hippocampal pyramidal cells (PCs) express many GABAAR subunit types and receive GABAergic inputs from distinct interneurons. Previous experiments revealed input-specific differences in α1 and α2 subunit densities in perisomatic synapses, suggesting distinct IPSC decay kinetics. However, IPSC decays evoked by axo-axonic, parvalbumin- or cholecystokinin-expressing basket cells were found to be similar. Using replica immunogold labeling, here we show that all CA1 PC somatic and AIS synapses contain the α1, α2, β1, β2, β3 and γ2 subunits...
2016: ELife
https://www.readbyqxmd.com/read/27512022/nonreciprocal-mechanisms-in-up-and-downregulation-of-spinal-motoneuron-excitability-by-modulators-of-kcnq-kv7-channels
#20
Joseph Lombardo, Melissa A Harrington
KCNQ/Kv7 channels form a slow noninactivating K(+) current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/Kv7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K(+) current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/Kv7 channel blockers...
November 1, 2016: Journal of Neurophysiology
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