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https://www.readbyqxmd.com/read/29474518/sestd1-encodes-a-developmentally-dynamic-synapse-protein-that-complexes-with-bcr-rac1-gap-to-regulate-forebrain-dendrite-spine-and-synapse-formation
#1
Xiao Yong Yang, Robert E Stanley, Adam P Ross, Aaron M Robitaille, John A Gray, Benjamin N R Cheyette
No abstract text is available yet for this article.
February 21, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29474348/downregulated-nuclear-factor-e2-related-factor-2-nrf2-aggravates-cognitive-impairments-via-neuroinflammation-and-synaptic-plasticity-in-the-senescence-accelerated-mouse-prone-8-samp8-mouse-a-model-of-accelerated-senescence
#2
Hui Ling Ren, Chao Nan Lv, Ying Xing, Yuan Geng, Feng Zhang, Wei Bu, Ming Wei Wang
BACKGROUND We observed the effects of nuclear factor E2-related factor 2 (Nrf2) downregulation via intrahippocampal injection of a lentiviral vector on cognition in senescence-accelerated mouse prone 8 (SAMP8) to investigate the role of the (Nrf2)/antioxidant response element (ARE) pathway in age-related changes. MATERIAL AND METHODS Control lentivirus and Nrf2-shRNA-lentivirus were separately injected into the hippocampus of 4-month-old SAMR1 and SAMP8 mice and then successfully downregulated Nrf2 expression in this brain region...
February 23, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29474316/autoantibodies-against-n-methyl-d-aspartate-receptor-1-in-health-and-disease
#3
Hannelore Ehrenreich
PURPOSE OF REVIEW: Humoral autoimmunity has gained highest interest in neurology and psychiatry. Despite numerous recent articles on this hot topic, however, the biological significance of natural autoantibodies (AB) and the normal autoimmune repertoire of mammals remained quite obscure. AB may contribute to disorder-relevant phenotypes and are even believed to induce diseases themselves, but the circumstances under which AB become pathogenic are not fully understood. This review will focus on the highly frequent AB against the N-methyl-d-aspartate receptor 1 (NMDAR1-AB) as an illustrating example and provide a critical overview of current work (please note that the new nomenclature, GluN1, is disregarded here for consistency with the AB literature)...
February 22, 2018: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29472837/spike-timing-dependent-plasticity-in-unipolar-silicon-oxide-rram-devices
#4
Konstantin Zarudnyi, Adnan Mehonic, Luca Montesi, Mark Buckwell, Stephen Hudziak, Anthony J Kenyon
Resistance switching, or Resistive RAM (RRAM) devices show considerable potential for application in hardware spiking neural networks (neuro-inspired computing) by mimicking some of the behavior of biological synapses, and hence enabling non-von Neumann computer architectures. Spike-timing dependent plasticity (STDP) is one such behavior, and one example of several classes of plasticity that are being examined with the aim of finding suitable algorithms for application in many computing tasks such as coincidence detection, classification and image recognition...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29470055/unique-molecular-regulation-of-higher-order-prefrontal-cortical-circuits-insights-into-the-neurobiology-of-schizophrenia
#5
Dibyadeep Datta, Amy F T Arnsten
Schizophrenia is associated with core deficits in cognitive abilities and impaired functioning of the newly evolved prefrontal association cortex (PFC). In particular, neuropathological studies of schizophrenia have found selective atrophy of the pyramidal cell microcircuits in deep layer III of the dorsolateral PFC (dlPFC), and compensatory weakening of related GABAergic interneurons. Studies in monkeys have shown that recurrent excitation in these layer III microcircuits generates the precisely patterned, persistent firing needed for working memory and abstract thought...
February 22, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29469093/multi-terminal-memtransistors-from-polycrystalline-monolayer-molybdenum-disulfide
#6
Vinod K Sangwan, Hong-Sub Lee, Hadallia Bergeron, Itamar Balla, Megan E Beck, Kan-Sheng Chen, Mark C Hersam
Memristors are two-terminal passive circuit elements that have been developed for use in non-volatile resistive random-access memory and may also be useful in neuromorphic computing. Memristors have higher endurance and faster read/write times than flash memory and can provide multi-bit data storage. However, although two-terminal memristors have demonstrated capacity for basic neural functions, synapses in the human brain outnumber neurons by more than a thousandfold, which implies that multi-terminal memristors are needed to perform complex functions such as heterosynaptic plasticity...
February 21, 2018: Nature
https://www.readbyqxmd.com/read/29469061/a-self-resetting-spiking-phase-change-neuron
#7
Rosie Cobley, Hasan Hayat, C David Wright
Neuromorphic, or brain-inspired, computing applications of phase-change devices have to date concentrated primarily on the implementation of phase-change synapses. However, the so-called accumulation mode of operation inherent in phase-change materials and devices can also be used to mimic the integrative properties of a biological neuron. Here we demonstrate, using physical modelling of nanoscale devices and SPICE modelling of associated circuits, that a single phase-change memory cell integrated into a comparator type circuit can deliver a basic hardware mimic of an integrate-and-fire spiking neuron with self-resetting capabilities...
February 22, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29467622/revisiting-the-role-of-clathrin-mediated-endoytosis-in-synaptic-vesicle-recycling
#8
REVIEW
Ira Milosevic
Without robust mechanisms to efficiently form new synaptic vesicles (SVs), the tens to hundreds of SVs typically present at the neuronal synapse would be rapidly used up, even at modest levels of neuronal activity. SV recycling is thus critical for synaptic physiology and proper function of sensory and nervous systems. Yet, more than four decades after it was originally proposed that the SVs are formed and recycled locally at the presynaptic terminals, the mechanisms of endocytic processes at the synapse are heavily debated...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29467607/understanding-the-generation-of-network-bursts-by-adaptive-oscillatory-neurons
#9
Tanguy Fardet, Mathieu Ballandras, Samuel Bottani, Stéphane Métens, Pascal Monceau
Experimental and numerical studies have revealed that isolated populations of oscillatory neurons can spontaneously synchronize and generate periodic bursts involving the whole network. Such a behavior has notably been observed for cultured neurons in rodent's cortex or hippocampus. We show here that a sufficient condition for this network bursting is the presence of an excitatory population of oscillatory neurons which displays spike-driven adaptation. We provide an analytic model to analyze network bursts generated by coupled adaptive exponential integrate-and-fire neurons...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29467497/altered-taok2-activity-causes-autism-related-neurodevelopmental-and-cognitive-abnormalities-through-rhoa-signaling
#10
Melanie Richter, Nadeem Murtaza, Robin Scharrenberg, Sean H White, Ole Johanns, Susan Walker, Ryan K C Yuen, Birgit Schwanke, Bianca Bedürftig, Melad Henis, Sarah Scharf, Vanessa Kraus, Ronja Dörk, Jakob Hellmann, Zsuzsa Lindenmaier, Jacob Ellegood, Henrike Hartung, Vickie Kwan, Jan Sedlacik, Jens Fiehler, Michaela Schweizer, Jason P Lerch, Ileana L Hanganu-Opatz, Fabio Morellini, Stephen W Scherer, Karun K Singh, Froylan Calderon de Anda
Atypical brain connectivity is a major contributor to the pathophysiology of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs). TAOK2 is one of several genes in the 16p11.2 microdeletion region, but whether it contributes to NDDs is unknown. We performed behavioral analysis on Taok2 heterozygous (Het) and knockout (KO) mice and found gene dosage-dependent impairments in cognition, anxiety, and social interaction. Taok2 Het and KO mice also have dosage-dependent abnormalities in brain size and neural connectivity in multiple regions, deficits in cortical layering, dendrite and synapse formation, and reduced excitatory neurotransmission...
February 21, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29467448/identification-of-the-fungal-ligand-triggering-cytotoxic-prr-mediated-nk-cell-killing-of-cryptococcus-and-candida
#11
Shu Shun Li, Henry Ogbomo, Michael K Mansour, Richard F Xiang, Lian Szabo, Fay Munro, Priyanka Mukherjee, Roy A Mariuzza, Matthias Amrein, Jatin M Vyas, Stephen M Robbins, Christopher H Mody
Natural killer (NK) cells use the activating receptor NKp30 as a microbial pattern-recognition receptor to recognize, activate cytolytic pathways, and directly kill the fungi Cryptococcus neoformans and Candida albicans. However, the fungal pathogen-associated molecular pattern (PAMP) that triggers NKp30-mediated killing remains to be identified. Here we show that β-1,3-glucan, a component of the fungal cell wall, binds to NKp30. We further demonstrate that β-1,3-glucan stimulates granule convergence and polarization, as shown by live cell imaging...
February 21, 2018: Nature Communications
https://www.readbyqxmd.com/read/29467254/bdnf-activates-an-nfi-dependent-neurodevelopmental-timing-program-by-sequestering-nfatc4
#12
Baojin Ding, Paul R Dobner, Debra Mullikin-Kilpatrick, Wei Wang, Hong Zhu, Chi-Wing Chow, John W Cave, Richard M Gronostajski, Daniel L Kilpatrick
How intrinsic and extrinsic signals are coordinated to regulate synaptic maturation and its timing is an important question for neurodevelopment and its disorders. Here, we investigated the influence of the neurotrophin BDNF on the developmental timing of a dendrite/synapse-related gene program controlled by Nuclear Factor One (NFI) in maturing cerebellar granule neurons (CGNs). BDNF accelerated the onset of NFI-regulated late-gene expression and NFI temporal occupancy in CGN cultures in a MEK5/ERK5-dependent manner...
February 21, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29466735/noninflammatory-changes-of-microglia-are-sufficient-to-cause-epilepsy
#13
Xiaofeng Zhao, Yuan Liao, Shannon Morgan, Ramkumar Mathur, Paul Feustel, Joseph Mazurkiewicz, Jiang Qian, Julia Chang, Gary W Mathern, Matthew A Adamo, Anthony L Ritaccio, Michael Gruenthal, Xinjun Zhu, Yunfei Huang
Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29466733/a%C3%A3-facilitates-ltd-at-schaffer-collateral-synapses-preferentially-in-the-left-hippocampus
#14
Kenneth J O'Riordan, Neng-Wei Hu, Michael J Rowan
Promotion of long-term depression (LTD) mechanisms by synaptotoxic soluble oligomers of amyloid-β (Aß) has been proposed to underlie synaptic dysfunction in Alzheimer's disease (AD). Previously, LTD was induced by relatively non-specific electrical stimulation. Exploiting optogenetics, we studied LTD using a more physiologically diffuse spatial pattern of selective pathway activation in the rat hippocampus in vivo. This relatively sparse synaptic LTD requires both the ion channel function and GluN2B subunit of the NMDA receptor but, in contrast to electrically induced LTD, is not facilitated by boosting endogenous muscarinic acetylcholine or metabotropic glutamate 5 receptor activation...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29466725/munc13-3-is-required-for-the-developmental-localization-of-ca-2-channels-to-active-zones-and-the-nanopositioning-of-ca-v-2-1-near-release-sensors
#15
Valentin Kusch, Grit Bornschein, Desiree Loreth, Julia Bank, Johannes Jordan, David Baur, Masahiko Watanabe, Akos Kulik, Manfred Heckmann, Jens Eilers, Hartmut Schmidt
Spatial relationships between Cav channels and release sensors at active zones (AZs) are a major determinant of synaptic fidelity. They are regulated developmentally, but the underlying molecular mechanisms are largely unclear. Here, we show that Munc13-3 regulates the density of Cav 2.1 and Cav 2.2 channels, alters the localization of Cav 2.1, and is required for the development of tight, nanodomain coupling at parallel-fiber AZs. We combined EGTA application and Ca2+ -channel pharmacology in electrophysiological and two-photon Ca2+ imaging experiments with quantitative freeze-fracture immunoelectron microscopy and mathematical modeling...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29466703/sapp%C3%AE-and-sapp%C3%AE-increase-structural-complexity-and-e-i-input-ratio-in-primary-hippocampal-neurons-and-alter-ca-2-homeostasis-and-creb1-signaling
#16
Raphael Hesse, Björn von Einem, Franziska Wagner, Patricia Bott, Daniel Schwanzar, Rosemary J Jackson, Karl Josef Föhr, Ludwig Lausser, Katja S Kroker, Christian Proepper, Paul Walther, Hans A Kestler, Tara L Spires-Jones, Tobias Boeckers, Holger Rosenbrock, Christine A F von Arnim
One major pathophysiological hallmark of Alzheimer's disease (AD) is senile plaques composed of amyloid β (Aβ). In the amyloidogenic pathway, cleavage of the amyloid precursor protein (APP) is shifted towards Aβ production and soluble APPβ (sAPPβ) levels. Aβ is known to impair synaptic function; however, much less is known about the physiological functions of sAPPβ. The neurotrophic properties of sAPPα, derived from the non-amyloidogenic pathway of APP cleavage, are well-established, whereas only a few, conflicting studies on sAPPβ exist...
February 18, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29464198/unraveling-synaptic-gcamp-signals-differential-excitability-and-clearance-mechanisms-underlying-distinct-ca-2-dynamics-in-tonic-and-phasic-excitatory-and-aminergic-modulatory-motor-terminals-in-drosophila
#17
Xiaomin Xing, Chun-Fang Wu
GCaMP is an optogenetic Ca2+ sensor widely used for monitoring neuronal activities but the precise physiological implications of GCaMP signals remain to be further delineated among functionally distinct synapses. The Drosophila neuromuscular junction (NMJ), a powerful genetic system for studying synaptic function and plasticity, consists of tonic and phasic glutamatergic and modulatory aminergic motor terminals of distinct properties. We report a first simultaneous imaging and electric recording study to directly contrast the frequency characteristics of GCaMP signals of the three synapses for physiological implications...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29464196/sequences-flanking-the-gephyrin-binding-site-of-glyr%C3%AE-tune-receptor-stabilization-at-synapses
#18
Nora Grünewald, Audric Jan, Charlotte Salvatico, Vanessa Kress, Marianne Renner, Antoine Triller, Christian G Specht, Guenter Schwarz
The efficacy of synaptic transmission is determined by the number of neurotransmitter receptors at synapses. Their recruitment depends upon the availability of postsynaptic scaffolding molecules that interact with specific binding sequences of the receptor. At inhibitory synapses, gephyrin is the major scaffold protein that mediates the accumulation of heteromeric glycine receptors (GlyRs) via the cytoplasmic loop in the β-subunit (β-loop). This binding involves high- and low-affinity interactions, but the molecular mechanism of this bimodal binding and its implication in GlyR stabilization at synapses remain unknown...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29464191/impact-of-nmda-receptor-overexpression-on-cerebellar-purkinje-cell-activity-and-motor-learning
#19
Elisa Galliano, Martijn Schonewille, Saša Peter, Mandy Rutteman, Simone Houtman, Dick Jaarsma, Freek E Hoebeek, Chris I De Zeeuw
In many brain regions involved in learning NMDA receptors (NMDARs) act as coincidence detectors of pre- and postsynaptic activity, mediating Hebbian plasticity. Intriguingly, the parallel fiber (PF) to Purkinje cell (PC) input in the cerebellar cortex, which is critical for procedural learning, shows virtually no postsynaptic NMDARs. Why is this? Here, we address this question by generating and testing independent transgenic lines that overexpress NMDAR containing the type 2B subunit (NR2B) specifically in PCs...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29464061/natural-and-molecular-history-of-prolactinoma-insights-from-a-prlr-mouse-model
#20
Valérie Bernard, Chiara Villa, Aurélie Auguste, Sophie Lamothe, Anne Guillou, Agnès Martin, Sandrine Caburet, Jacques Young, Reiner A Veitia, Nadine Binart
Lactotroph adenoma, also called prolactinoma, is the most common pituitary tumor but little is known about its pathogenesis. Mouse models of prolactinoma can be useful to better understand molecular mechanisms involved in abnormal lactotroph cell proliferation and secretion. We have previously developed a prolactin receptor deficient ( Prlr -/- ) mouse, which develops prolactinoma. The present study aims to explore the natural history of prolactinoma formation in Prlr -/- mice, using hormonal, radiological, histological and molecular analyses to uncover mechanisms involved in lactotroph adenoma development...
January 19, 2018: Oncotarget
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