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https://www.readbyqxmd.com/read/28103481/motor-learning-requires-purkinje-cell-synaptic-potentiation-through-activation-of-ampa-receptor-subunit-glua3
#1
Nicolas Gutierrez-Castellanos, Carla M Da Silva-Matos, Kuikui Zhou, Cathrin B Canto, Maria C Renner, Linda M C Koene, Ozgecan Ozyildirim, Rolf Sprengel, Helmut W Kessels, Chris I De Zeeuw
Accumulating evidence indicates that cerebellar long-term potentiation (LTP) is necessary for procedural learning. However, little is known about its underlying molecular mechanisms. Whereas AMPA receptor (AMPAR) subunit rules for synaptic plasticity have been extensively studied in relation to declarative learning, it is unclear whether these rules apply to cerebellum-dependent motor learning. Here we show that LTP at the parallel-fiber-to-Purkinje-cell synapse and adaptation of the vestibulo-ocular reflex depend not on GluA1- but on GluA3-containing AMPARs...
January 18, 2017: Neuron
https://www.readbyqxmd.com/read/28100586/axon-termination-pruning-and-synaptogenesis-in-the-giant-fiber-system-of-drosophila-melanogaster-is-promoted-by-highwire
#2
Melissa Borgen, Kimberly Rowland, Jana Boerner, Brandon Lloyd, Aruna Khan, Rod Murphey
The ubiquitin ligase Highwire has a conserved role in synapse formation. Here we show that Highwire coordinates several facets of central synapse formation in the Drosophila melanogaster giant fiber system, including axon termination, axon pruning, and synaptic function. Despite the similarities to the fly neuromuscular junction, the role of Highwire and the underlying signaling pathways are distinct in the fly's giant fiber system. During development, branching of the giant fiber presynaptic terminal occurs and, normally, the transient branches are pruned away...
January 18, 2017: Genetics
https://www.readbyqxmd.com/read/28094782/cocaine-enhances-dc-to-t-cell-hiv-1-transmission-by-activating-dc-sign-larg-lsp1-complex-and-facilitating-infectious-synapse-formation
#3
Anil Prasad, Rutuja Kulkarni, Shuxian Jiang, Jerome E Groopman
DC-SIGN is a dendritic cell surface structure which participates in binding and transmission of HIV-1. Here, for the first time we demonstrate that cocaine induces over expression of DC-SIGN and significantly enhances virus transfer from DCs to T-cells by increasing the binding and internalization of HIV-1 in DCs. We found that cocaine activates a DC-SIGN mediated 'signalosome' complex by enhancing its association with LARG and LSP1. Further, LARG was observed to participate in DC-SIGN mediated internalization of HIV-1 in DCs...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092659/rem-sleep-selectively-prunes-and-maintains-new-synapses-in-development-and-learning
#4
Wei Li, Lei Ma, Guang Yang, Wen-Biao Gan
The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning...
January 16, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28087764/accumulation-of-polyribosomes-in-dendritic-spine-heads-but-not-bases-and-necks-during-memory-consolidation-depends-on-cap-dependent-translation-initiation
#5
Linnaea E Ostroff, Benjamin Botsford, Sofya Gindina, Kiriana K Cowansage, Joseph E LeDoux, Eric Klann, Charles Hoeffer
: Translation in dendrites is believed to support synaptic changes during memory consolidation. Although translational control mechanisms are fundamental mediators of memory, little is known about their role in local translation. We previously found that polyribosomes accumulate in dendritic spines of the adult rat lateral amygdala (LA) during consolidation of aversive Pavlovian conditioning, and that this memory requires cap-dependent initiation, a primary point of translational control in eukaryotic cells...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28081563/interactions-with-astroglia-influence-the-shape-of-the-developing-dendritic-arbor-and-restrict-dendrite-growth-independent-of-promoting-synaptic-contacts
#6
Ginger S Withers, Jennifer R Farley, Jeffrey R Sterritt, Andrés B Crane, Christopher S Wallace
Astroglia play key roles in the development of neurons, ranging from regulating neuron survival to promoting synapse formation, yet basic questions remain about whether astrocytes might be involved in forming the dendritic arbor. Here, we used cultured hippocampal neurons as a simple in vitro model that allowed dendritic growth and geometry to be analyzed quantitatively under conditions where the extent of interactions between neurons and astrocytes varied. When astroglia were proximal to neurons, dendrites and dendritic filopodia oriented toward them, but the general presence of astroglia significantly reduced overall dendrite growth...
2017: PloS One
https://www.readbyqxmd.com/read/28077511/altered-connectivity-and-synapse-maturation-of-the-hippocampal-mossy-fiber-pathway-in-a-mouse-model-of-the-fragile-x-syndrome
#7
F Scharkowski, Michael Frotscher, David Lutz, Martin Korte, Kristin Michaelsen-Preusse
The Fragile X syndrome (FXS) as the most common monogenetic cause of cognitive impairment and autism indicates how tightly the dysregulation of synapse development is linked to cognitive deficits. Symptoms of FXS include excessive adherence to patterns that point to compromised hippocampal network formation. Surprisingly, one of the most complex hippocampal synapses connecting the dentate gyrus (DG) to CA3 pyramidal neurons has not been analyzed in FXS yet. Intriguingly, we found altered synaptic function between DG and CA3 in a mouse model of FXS (fmr1 knockout [KO]) demonstrated by increased mossy fiber-dependent miniature excitatory postsynaptic current (mEPSC) frequency at CA3 pyramidal neurons together with increased connectivity between granule cells and CA3 neurons...
January 10, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28073939/nanoscale-molecular-reorganization-of-the-inhibitory-postsynaptic-density-is-a-determinant-of-gabaergic-synaptic-potentiation
#8
Francesca Pennacchietti, Sebastiano Vascon, Thierry Nieus, Christian Rosillo, Sabyasachi Das, Shiva Tyagarajan, Alberto Diaspro, Alessio Del Bue, Enrica Maria Petrini, Andrea Barberis, Francesca Cella Zanacchi
: Gephyrin is a key scaffold protein mediating the anchoring of GABAA receptors at inhibitory synapses. Here we exploited super-resolution techniques combined with proximity-based clustering analysis and model simulations to investigate the single molecule gephyrin reorganization during plasticity of inhibitory synapses in mouse hippocampal cultured neurons. This approach revealed that during the expression of inhibitory long-term potentiation the increase of gephyrin density at postsynaptic sites is associated with the promoted formation of gephyrin nano-domains...
January 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069867/the-carboxyl-terminal-region-of-dok-7-plays-a-key-but-not-essential-role-in-activation-of-muscle-specific-receptor-kinase-musk-and-neuromuscular-synapse-formation
#9
Ryo Ueta, Tohru Tezuka, Yosuke Izawa, Sadanori Miyoshi, Satoru Nagatoishi, Kouhei Tsumoto, Yuji Yamanashi
As the synapse between a motor neuron and skeletal muscle, the neuromuscular junction (NMJ) is required for muscle contraction. The formation and maintenance of NMJs are controlled by the muscle-specific receptor kinase MuSK. Dok-7 is the essential cytoplasmic activator of MuSK, and indeed mice lacking Dok-7 form no NMJs. Moreover, DOK7 gene mutations underlie DOK7 myasthenia, an NMJ synaptopathy. Previously, we failed to detect MuSK activation in myotubes by Dok-7 mutated in the N-terminal pleckstrin homology (PH) or phosphotyrosine binding (PTB) domain or that lacked the C-terminal region (Dok-7-ΔC)...
January 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28067168/sumoylation-in-neurological-diseases
#10
F-Y Liu, Y-F Liu, Y Yang, Z-W Luo, J-W Xiang, Z-G Chen, R-L Qi, T-H Yang, Y Xiao, W-J Qing, D W-C Li
Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important post-translational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases...
January 9, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28064005/three-dimensional-functional-human-neuronal-networks-in-uncompressed-low-density-electrospun-fiber-scaffolds
#11
Albin Jakobsson, Maximilian Ottosson, Marina Castro Zalis, David O'Carroll, Ulrica Englund Johansson, Fredrik Johansson
We demonstrate an artificial three-dimensional (3D) electrical active human neuronal network system, by the growth of brain neural progenitors in highly porous low density electrospun poly-ε-caprolactone (PCL) fiber scaffolds. In neuroscience research cell-based assays are important experimental instruments for studying neuronal function in health and disease. Traditional cell culture at 2D-surfaces induces abnormal cell-cell contacts and network formation. Hence, there is a tremendous need to explore in vivo-resembling 3D neural cell culture approaches...
January 4, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28057866/evidence-for-opposing-roles-of-celsr3-and-vangl2-in-glutamatergic-synapse-formation
#12
Sonal Thakar, Liqing Wang, Ting Yu, Mao Ye, Keisuke Onishi, John Scott, Jiaxuan Qi, Catarina Fernandes, Xuemei Han, John R Yates, Darwin K Berg, Yimin Zou
The signaling mechanisms that choreograph the assembly of the highly asymmetric pre- and postsynaptic structures are still poorly defined. Using synaptosome fractionation, immunostaining, and coimmunoprecipitation, we found that Celsr3 and Vangl2, core components of the planar cell polarity (PCP) pathway, are localized at developing glutamatergic synapses and interact with key synaptic proteins. Pyramidal neurons from the hippocampus of Celsr3 knockout mice exhibit loss of ∼50% of glutamatergic synapses, but not inhibitory synapses, in culture...
January 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28057175/pour-comprendre-l%C3%A2-activation-lymphocytaire-t
#13
Jeanne Galaine, Yann Godet, Olivier Adotévi
T cells activation is a finely regulated process to establish an effective anti-infectious or antitumor immune response while avoiding harmful autoimmune reactions. Although T cells are considered to be the main protagonists of the antitumor immune response, they act in interaction with other immune cells. The meeting of naive T cells with dendritic cells induces their differentiation into effector cells following the recognition of the peptide-MHC complex by the T cell receptor. The interaction of costimulatory molecules present on the surface of T cells with their ligand (s) expressed by mature dendritic cells contribute to the optimal T cell activation and to the formation of the immunological synapse...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28050794/heterogeneity-in-synaptogenic-profile-of-astrocytes-from-different-brain-regions
#14
Andrea Schmidt Buosi, Isadora Matias, Ana Paula Bergamo Araujo, Carolina Batista, Flávia Carvalho Alcantara Gomes
Astrocytes, the most abundant glial cells in the central nervous system (CNS), comprise a heterogeneous population of cells. However, how this heterogeneity impacts their function within brain homeostasis and response to injury and disease is still largely unknown. Recently, astrocytes have been recognized as important regulators of synapse formation and maturation. Here, we analyzed the synaptogenic property of astrocytes from different regions of the CNS. The effect of conditioned medium derived from astrocytes (astrocyte-conditioned medium (ACM)) from cerebral cortex, hippocampus, midbrain and cerebellum, in synapse formation, was evaluated...
January 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28045486/mimicking-neuroligin-2-functions-in-%C3%AE-cells-by-functionalized-nanoparticles-as-a-novel-approach-for-antidiabetic-therapy
#15
Anna Munder, Liron L Israel, Shirin Kahremany, Rina Ben-Shabat-Binyamini, Charles Zhang, Michal Kolitz-Domb, Olga Viskind, Anna Levine, Hanoch Senderowitz, Steven Chessler, Jean-Paul Lellouche, Arie Gruzman
Both pancreatic β-cell membranes and presynaptic active zones of neurons include in their structures similar protein complexes, which are responsible for mediating the secretion of bioactive molecules. In addition, these membrane-anchored proteins regulate interactions between neurons and guide the formation and maturation of synapses. These proteins include the neuroligins (e.g., NL-2) and their binding partners, the neurexins. The insulin secretion and maturation of β-cells is known to depend on their 3-dimensional (3D) arrangement...
January 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28041940/roles-of-afadin-in-the-formation-of-the-cellular-architecture-of-the-mouse-hippocampus-and-dentate-gyrus
#16
Muneaki Miyata, Tomohiko Maruo, Aika Kaito, Shujie Wang, Hideaki Yamamoto, Takeshi Fujiwara, Akira Mizoguchi, Kenji Mandai, Yoshimi Takai
The hippocampal formation with tightly packed neurons, mainly at the dentate gyrus, CA3, CA2, and CA1 regions, constitutes a one-way neural circuit, which is associated with learning and memory. We previously showed that the cell adhesion molecules nectins and its binding protein afadin play roles in the formation of the mossy fiber synapses which are formed between the mossy fibers of the dentate gyrus granule cells and the dendrites of the CA3 pyramidal cells. We showed here that in the afadin-deficient hippocampal formation, the dentate gyrus granules cells and the CA3, CA2, and CA1 pyramidal cells were abnormally located; the mossy fiber trajectory was abnormally elongated; the CA3 pyramidal cells were abnormally differentiated; and the densities of the presynaptic boutons on the mossy fibers and the apical dendrites of the CA3 pyramidal cells were decreased...
December 29, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28039324/topoisomerase-3%C3%AE-is-the-major-topoisomerase-for-mrnas-and-linked-to-neurodevelopment-and-mental-dysfunction
#17
Muzammil Ahmad, Weiping Shen, Wen Li, Yutong Xue, Sige Zou, Dongyi Xu, Weidong Wang
Human cells contain five topoisomerases in the nucleus and cytoplasm, but which one is the major topoisomerase for mRNAs is unclear. To date, Top3β is the only known topoisomerase that possesses RNA topoisomerase activity, binds mRNA translation machinery and interacts with an RNA-binding protein, FMRP, to promote synapse formation; and Top3β gene deletion has been linked to schizophrenia. Here, we show that Top3β is also the most abundant mRNA-binding topoisomerase in cells. Top3β, but not other topoisomerases, contains a distinctive RNA-binding domain; and deletion of this domain diminishes the amount of Top3β that associates with mRNAs, indicating that Top3β is specifically targeted to mRNAs by its RNA binding domain...
December 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/28038685/grafted-c-kit-ssea1-eye-wall-progenitor-cells-delay-retinal-degeneration-in-mice-by-regulating-neural-plasticity-and-forming-new-graft-to-host-synapses
#18
Xi Chen, Zehua Chen, Zhengya Li, Chen Zhao, Yuxiao Zeng, Ting Zou, Caiyun Fu, Xiaoli Liu, Haiwei Xu, Zheng Qin Yin
BACKGROUND: Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry...
December 30, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28036020/bispecific-antibodies-as-a-development-platform-for-new-concepts-and-treatment-strategies
#19
REVIEW
Fa Yang, Weihong Wen, Weijun Qin
With the development of molecular cloning technology and the deep understanding of antibody engineering, there are diverse bispecific antibody formats from which to choose to pursue the optimal biological activity and clinical purpose. The single-chain-based bispecific antibodies usually bridge tumor cells with immune cells and form an immunological synapse because of their relatively small size. Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all of which have an extended blood half-life and their own crystalline fragment (Fc)-mediated functions...
December 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28035928/consecutive-analysis-of-bace1-function-on-developing-and-developed-neuronal-cells
#20
Yuji Kamikubo, Nobumasa Takasugi, Kazue Niisato, Yoshie Hashimoto, Takashi Sakurai
The amyloid-β protein precursor (AβPP) is cleaved by a transmembrane protease termed β-site AβPP cleavage enzyme (BACE1), which is being explored as a target for therapy and prevention of Alzheimer's disease (AD). Although genetic deletion of BACE1 results in abolished amyloid pathology in AD model mice, it also results in neurodevelopmental phenotypes such as hypomyelination and synaptic loss, observed in schizophrenia and autism-like phenotype. These lines of evidence indicate that the inhibition of BACE1 causes adverse side effects during the neurodevelopmental stage...
December 30, 2016: Journal of Alzheimer's Disease: JAD
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