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https://www.readbyqxmd.com/read/29355968/the-unfolding-landscape-of-the-congenital-myasthenic-syndromes
#1
REVIEW
Andrew G Engel, Xin-Ming Shen, Duygu Selcen
Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is impaired by one or more specific mechanisms. Since the advent of next-generation sequencing methods, the discovery of novel CMS targets and phenotypes has proceeded at an accelerated rate. Here, we review the current classification of CMS and describe our findings in five of these targets identified and investigated in our laboratory in the past 5 years. Defects in LRP4 hinder synaptic development and maintenance; the defects in PREPL are predicted to diminish filling of the synaptic vesicle with acetylcholine; and defects in SNAP25, Munc13-1, and synaptotbrevin-1 impede synaptic vesicle exocytosis...
January 21, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29355733/a-new-approach-to-detect-the-coding-rule-of-the-cortical-spiking-model-in-the-information-transmission
#2
Soheila Nazari, Karim Faez, Mahyar Janahmadi
Investigation of the role of the local field potential (LFP) fluctuations in encoding the received sensory information by the nervous system remains largely unknown. On the other hand, transmission of these translation rules in information transmission between the structure of sensory stimuli and the cortical oscillations to the bio-inspired artificial neural networks operating at the efficiency of the nervous system is still a vague puzzle. In order to move towards this important goal, computational neuroscience tools can be useful so, we simulated a large-scale network of excitatory and inhibitory spiking neurons with synaptic connections consisting of AMPA and GABA currents as a model of cortical populations...
January 3, 2018: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/29355693/genetic-deletion-of-nmda-receptors-suppresses-gabaergic-synaptic-transmission-in-two-distinct-types-of-central-neurons
#3
Xinglong Gu, Wei Lu
NMDA-type ionotropic glutamate receptors (NMDARs) play an important role in the regulation of synapse development and function in the brain. Recently we have shown that NMDARs are critical for GABAergic synapse development in developing hippocampal neurons. However, it remains unclear whether NMDARs are important for establishment of GABAergic synaptic transmission in other types of neurons in the brain. Here we report that in both cortical pyramidal neurons and midbrain dopamine neurons in ventral tegmental area (VTA), genetic deletion of the GluN1 subunit, which is required for assembly of functional NMDARs, leads to a strong reduction of GABAergic synaptic transmission...
January 17, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29355673/a-role-for-ca3-in-social-recognition-memory
#4
Ming-Ching Chiang, Arthur J Y Huang, Marie E Wintzer, Toshio Ohshima, Thomas J McHugh
Social recognition memory is crucial for survival across species, underlying the need to correctly identify conspecifics, mates and potential enemies. In humans the hippocampus is engaged in social and episodic memory, however the circuit mechanisms of social memory in rodent models has only recently come under scrutiny. Work in mice has established that the dorsal CA2 and ventral CA1 regions play critical roles, however a more comprehensive comparative analyses of the circuits and mechanisms required has not been reported...
January 17, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29353373/disturbance-of-metabotropic-glutamate-receptor-mediated-long-term-depression-mglu-ltd-of-excitatory-synaptic-transmission-in-the-rat-hippocampus-after-prenatal-immune-challenge
#5
Mélanie Cavalier, Azza Ben Sedrine, Lea Thevenet, Nadine Crouzin, Janique Guiramand, Marie-Céleste de Jésus Ferreira, Catherine Cohen-Solal, Gérard Barbanel, Michel Vignes
Maternal immune challenge has proved to induce moderate to severe behavioral disabilities in the offspring. Cognitive/behavioral deficits are supported by changes in synaptic plasticity in different brain areas. We have reported previously that prenatal exposure to bacterial LPS could induce inhibition of hippocampal long-term potentiation (LTP) in the CA1 area of the juvenile/adult male offspring associated with spatial learning inabilities. Nevertheless, deficits in plasticity could be observed at earlier stages as shown by the early loss of long-term depression (LTD) in immature animals...
January 20, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29352468/developmental-plasticity-of-gabaergic-neurotransmission-to-brainstem-motoneurons
#6
Lila Buls Wollman, Richard B Levine, Ralph F Fregosi
Nicotinic acetylcholine receptor (nAChR) signalling regulates neuronal differentiation and synaptogenesis. Here we test the hypothesis that developmental nicotine exposure (DNE) disrupts the development of GABAergic synaptic transmission to hypoglossal motoneurons (XIIMNs). GABAergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC/mIPSC) were recorded from XIIMNs in brainstem slices from control and DNE rat pups of either sex, 1-5 days old, at baseline and following acute stimulation of nAChRs with nicotine...
January 20, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29352267/differential-susceptibility-of-striatal-hippocampal-and-cortical-neurons-to-caspase-6
#7
Anastasia Noël, Libin Zhou, Bénédicte Foveau, P Jesper Sjöström, Andréa C LeBlanc
Active cysteinyl protease Caspase-6 is associated with early Alzheimer and Huntington diseases. Higher entorhinal cortex and hippocampal Caspase-6 levels correlate with lower cognitive performance in aged humans. Caspase-6 induces axonal degeneration in human primary neuron cultures and causes inflammation and neurodegeneration in mouse hippocampus, and age-dependent memory impairment. To assess whether Caspase-6 causes damage to another neuronal system, a transgenic knock-in mouse overexpressing a self-activated form of Caspase-6 five-fold in the striatum, the area affected in Huntington disease, and 2...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352169/chaski-a-novel-drosophila-lactate-pyruvate-transporter-required-in-glia-cells-for-survival-under-nutritional-stress
#8
María Graciela Delgado, Carlos Oliva, Estefanía López, Andrés Ibacache, Alex Galaz, Ricardo Delgado, L Felipe Barros, Jimena Sierralta
The intercellular transport of lactate is crucial for the astrocyte-to-neuron lactate shuttle (ANLS), a model of brain energetics according to which neurons are fueled by astrocytic lactate. In this study we show that the Drosophila chaski gene encodes a monocarboxylate transporter protein (MCT/SLC16A) which functions as a lactate/pyruvate transporter, as demonstrated by heterologous expression in mammalian cell culture using a genetically encoded FRET nanosensor. chaski expression is prominent in the Drosophila central nervous system and it is particularly enriched in glia over neurons...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29349630/developmental-changes-in-serotonergic-modulation-of-gabaergic-synaptic-transmission-and-postsynaptic-gabaa-receptor-composition-in-the-cerebellar-nuclei
#9
Fumihito Saitow, Masatoshi Nagano, Hidenori Suzuki
Outputs from the cerebellar nuclei (CN) are important for generating and controlling movement. The activity of CN neurons is controlled not only by excitatory inputs from mossy and climbing fibers and by γ-aminobutyric acid (GABA)-based inhibitory transmission from Purkinje cells in the cerebellar cortex but is also modulated by inputs from other brain regions, including serotonergic fibers that originate in the dorsal raphe nuclei. We examined the modulatory effects of serotonin (5-HT) on GABAergic synapses during development, using rat cerebellar slices...
January 19, 2018: Cerebellum
https://www.readbyqxmd.com/read/29348594/myelination-of-purkinje-axons-is-critical-for-resilient-synaptic-transmission-in-the-deep-cerebellar-nucleus
#10
Tara Barron, Julia Saifetiarova, Manzoor A Bhat, Jun Hee Kim
The roles of myelin in maintaining axonal integrity and action potential (AP) propagation are well established, but its role in synapse maintenance and neurotransmission remains largely understudied. Here, we investigated how Purkinje axon myelination regulates synaptic transmission in the Purkinje to deep cerebellar nuclei (DCN) synapses using the Long Evans Shaker (LES) rat, which lacks compact myelin and thus displays severe locomotion deficits. DCN neurons fired spontaneous action potentials (APs), whose frequencies were dependent on the extent of myelin...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348575/quantitative-optical-nanophysiology-of-ca2-signaling-at-inner-hair-cell-active-zones
#11
Jakob Neef, Nicolai T Urban, Tzu-Lun Ohn, Thomas Frank, Philippe Jean, Stefan W Hell, Katrin I Willig, Tobias Moser
Ca2+ influx triggers the release of synaptic vesicles at the presynaptic active zone (AZ). A quantitative characterization of presynaptic Ca2+ signaling is critical for understanding synaptic transmission. However, this has remained challenging to establish at the required resolution. Here, we employ confocal and stimulated emission depletion (STED) microscopy to quantify the number (20-330) and arrangement (mostly linear 70 nm × 100-600 nm clusters) of Ca2+ channels at AZs of mouse cochlear inner hair cells (IHCs)...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29346754/input-specific-nmdar-dependent-potentiation-of-dendritic-gabaergic-inhibition
#12
Chiayu Q Chiu, James S Martenson, Maya Yamazaki, Rie Natsume, Kenji Sakimura, Susumu Tomita, Steven J Tavalin, Michael J Higley
Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors leads to input-specific long-term potentiation of dendritic inhibition mediated by somatostatin-expressing interneurons...
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29343455/adolescent-social-stress-increases-anxiety-like-behavior-and-alters-synaptic-transmission-without-influencing-nicotine-responses-in-a-sex-dependent-manner
#13
Michael J Caruso, Nicole A Crowley, Dana E Reiss, Jasmine I Caulfield, Bernhard Luscher, Sonia A Cavigelli, Helen M Kamens
Early-life stress is a risk factor for comorbid anxiety and nicotine use. Because little is known about the factors underlying this comorbidity, we investigated the effects of adolescent stress on anxiety-like behavior and nicotine responses within individual animals. Adolescent male and female C57BL/6J mice were exposed to chronic variable social stress (CVSS; repeated cycles of social isolation + social reorganization) or control conditions from postnatal days (PND) 25-59. Anxiety-like behavior and social avoidance were measured in the elevated plus-maze (PND 61-65) and social approach-avoidance test (Experiment 1: PND 140-144; Experiment 2: 95-97), respectively...
January 14, 2018: Neuroscience
https://www.readbyqxmd.com/read/29342042/long-term-administration-of-salicylate-induced-changes-in-bdnf-expression-and-creb-phosphorylation-in-the-auditory-cortex-of-rats
#14
Bin Yi, Cong Wu, Runjie Shi, Kun Han, Haibin Sheng, Bei Li, Ling Mei, Xueling Wang, Zhiwu Huang, Hao Wu
HYPOTHESIS: We investigated whether salicylate induces tinnitus through alteration of the expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding protein (CREB), and phosphorylated CREB (p-CREB) in the auditory cortex (AC). BACKGROUND: Salicylate medication is frequently used for long-term treatment in clinical settings, but it may cause reversible tinnitus. Salicylate-induced tinnitus is associated with changes related to central auditory neuroplasticity...
January 16, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29341884/acute-stress-persistently-alters-locus-coeruleus-function-and-anxiety-like-behavior-in-adolescent-rats
#15
Olga Borodovitsyna, Matthew D Flamini, Daniel J Chandler
Stress is a physiological state characterized by altered neuroendocrine signaling, behavioral arousal, and anxiety. Chronic or traumatic stress may predispose individuals for multiple somatic and psychiatric illnesses. The locus coeruleus (LC) is a major node in the stress response that integrates input from multiple stress responsive neural circuits and releases norepinephrine throughout the central nervous system to promote vigilance and anxiety. Many mood disorders associated with prior stress are characterized by chronically altered noradrenergic signaling, yet the long-term impact of an acute stressor on LC function is not clear...
January 13, 2018: Neuroscience
https://www.readbyqxmd.com/read/29337241/differential-effects-of-alzheimer-s-disease-a%C3%AE-40-and-42-on-endocytosis-and-intraneuronal-trafficking
#16
Rajesh S Omtri, Kevin Thompson, Xiojia Tang, Chaitanya C Gali, Ute Panzenboeck, Michael W Davidson, Krishna R Kalari, Karunya K Kadimalla
Anomalous neuronal accumulation of Aβ peptides was shown to affect synaptic transmission and contribute to neurodegeneration in Alzheimer's disease (AD) brain. Neuronal cells internalize amyloid beta (Aβ) peptides from the brain extracellular space even under normal physiological conditions, and these endocytotic pathways go awry during AD progression. We hypothesized that exposure to toxic Aβ species accumulating in AD brain contribute to perturbations in neuronal endocytosis. We have shown substantial down-regulation of KEGG endocytotic pathway genes in AD patient brain regions that accumulate Aβ compared to those in non-demented individuals...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29335828/low-but-not-high-doses-of-copper-sulfate-impair-synaptic-plasticity-in-the-hippocampal-ca1-region-in-vivo
#17
Abolfazl Jand, Mohammad Reza Taheri-Nejad, Masoumeh Mosleh, Mohammad Reza Palizvan
Previous studies have shown the inhibitory effect of the in vitro application of copper sulfate on hippocampal long-term potentiation. While in vivo administration of copper did not affect spatial learning and memory. To find possible answers to this controversial issue, we evaluate the effect of different doses of copper sulfate on in vivo long-term potentiation, synaptic transmission, and paired-pulse behavior of CA1 pyramidal cells. Thirty-two male Wistar rats were divided into four groups: control, 5, 10, and 15 mg of copper sulfate...
January 15, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29334986/bridging-pro-inflammatory-signals-synaptic-transmission-and-protection-in-spinal-explants-in-vitro
#18
M Medelin, V Giacco, A Aldinucci, G Castronovo, E Bonechi, A Sibilla, M Tanturli, M Torcia, L Ballerini, F Cozzolino, C Ballerini
Multiple sclerosis is characterized by tissue atrophy involving the brain and the spinal cord, where reactive inflammation contributes to the neurodegenerative processes. Recently, the presence of synapse alterations induced by the inflammatory responses was suggested by experimental and clinical observations, in experimental autoimmune encephalomyelitis mouse model and in patients, respectively. Further knowledge on the interplay between pro-inflammatory agents, neuroglia and synaptic dysfunction is crucial to the design of unconventional protective molecules...
January 15, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29333676/ether-%C3%A3-go-go-k-channels-effective-modulators-of-neuronal-excitability
#19
Christiane K Bauer, Jürgen R Schwarz
Mammalian EAG (ether-à-go-go) channels are voltage-gated K+ channels. They are encoded by the KCNH gene family and divided into three subfamilies, eag (Kv10), erg (eag-related gene; Kv11) and elk (eag-like; Kv12). All EAG channel subtypes are expressed in the brain where they effectively modulate neuronal excitability. This Topical Review describes the biophysical properties of each of the EAG channel subtypes, their function in neurons and the neurological diseases induced by EAG channel mutations. In contrast to the function of erg currents in the heart where they contribute to repolarization of the cardiac action potential, erg currents in neurons are involved in the maintenance of the resting potential, setting of action potential threshold and frequency accommodation...
January 15, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29330091/cdc42ep4-a-perisynaptic-scaffold-protein-in-bergmann-glia-is-required-for-glutamatergic-tripartite-synapse-configuration
#20
Natsumi Ageta-Ishihara, Kohtarou Konno, Maya Yamazaki, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Makoto Kinoshita
Configuration of tripartite synapses, comprising the pre-, post-, and peri-synaptic components (axon terminal or bouton, dendritic spine, and astroglial terminal process), is a critical determinant of neurotransmitter kinetics and hence synaptic transmission. However, little is known about molecular basis for the regulation of tripartite synapse morphology. Previous studies showed that CDC42EP4, an effector protein of a cell morphogenesis regulator CDC42, is expressed exclusively in Bergmann glia in the cerebellar cortex, that it forms tight complex with the septin heterooligomer, and that it interacts indirectly with the glutamate transporter GLAST and MYH10/nonmuscle myosin ΙΙB...
January 9, 2018: Neurochemistry International
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