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https://www.readbyqxmd.com/read/27926876/potentiation-of-synaptic-glun2b-nmdar-currents-by-fyn-kinase-is-gated-through-bdnf-mediated-disinhibition-in-spinal-pain-processing
#1
Michael E Hildebrand, Jian Xu, Annemarie Dedek, Yi Li, Ameet S Sengar, Simon Beggs, Paul J Lombroso, Michael W Salter
In chronic pain states, the neurotrophin brain-derived neurotrophic factor (BDNF) transforms the output of lamina I spinal neurons by decreasing synaptic inhibition. Pain hypersensitivity also depends on N-methyl-D-aspartate receptors (NMDARs) and Src-family kinases, but the locus of NMDAR dysregulation remains unknown. Here, we show that NMDAR-mediated currents at lamina I synapses are potentiated in a peripheral nerve injury model of neuropathic pain. We find that BDNF mediates NMDAR potentiation through activation of TrkB and phosphorylation of the GluN2B subunit by the Src-family kinase Fyn...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926833/conformational-plasticity-in-the-transsynaptic-neurexin-cerebellin-glutamate-receptor-adhesion-complex
#2
Shouqiang Cheng, Alpay B Seven, Jing Wang, Georgios Skiniotis, Engin Özkan
Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein cerebellin with pre-synaptic neurexin and post-synaptic delta-type glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of α- and β-neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain...
December 6, 2016: Structure
https://www.readbyqxmd.com/read/27924869/asic1a-regulates-insular-long-term-depression-and-is-required-for-the-extinction-of-conditioned-taste-aversion
#3
Wei-Guang Li, Ming-Gang Liu, Shining Deng, Yan-Mei Liu, Lin Shang, Jing Ding, Tsan-Ting Hsu, Qin Jiang, Ying Li, Fei Li, Michael Xi Zhu, Tian-Le Xu
Acid-sensing ion channel 1a (ASIC1a) has been shown to play important roles in synaptic plasticity, learning and memory. Here we identify a crucial role for ASIC1a in long-term depression (LTD) at mouse insular synapses. Genetic ablation and pharmacological inhibition of ASIC1a reduced the induction probability of LTD without affecting that of long-term potentiation in the insular cortex. The disruption of ASIC1a also attenuated the extinction of established taste aversion memory without altering the initial associative taste learning or its long-term retention...
December 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27924838/excitatory-post-synaptic-potential-mimicked-in-indium-zinc-oxide-synaptic-transistors-gated-by-methyl-cellulose-solid-electrolyte
#4
Liqiang Guo, Juan Wen, Jianning Ding, Changjin Wan, Guanggui Cheng
The excitatory postsynaptic potential (EPSP) of biological synapses is mimicked in indium-zinc-oxide synaptic transistors gated by methyl cellulose solid electrolyte. These synaptic transistors show excellent electrical performance at an operating voltage of 0.8 V, Ion/off ratio of 2.5 × 10(6), and mobility of 38.4 cm(2)/Vs. After this device is connected to a resistance of 4 MΩ in series, it exhibits excellent characteristics as an inverter. A threshold potential of 0.3 V is achieved by changing the gate pulse amplitude, width, or number, which is analogous to biological EPSP...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27923880/b-cell-antigen-extraction-is-regulated-by-physical-properties-of-antigen-presenting-cells
#5
Katelyn M Spillane, Pavel Tolar
Antibody production and affinity maturation are driven by B cell extraction and internalization of antigen from immune synapses. However, the extraction mechanism remains poorly understood. Here we develop DNA-based nanosensors to interrogate two previously proposed mechanisms, enzymatic liberation and mechanical force. Using antigens presented by either artificial substrates or live cells, we show that B cells primarily use force-dependent extraction and resort to enzymatic liberation only if mechanical forces fail to retrieve antigen...
December 6, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27923561/neuropathology-and-neurobehavioral-alterations-in-a-rat-model-of-traumatic-brain-injury-to-occupants-of-vehicles-targeted-by-underbody-blasts
#6
Flaubert Tchantchou, William L Fourney, Ulrich H Leist, Joshua Vaughan, Parisa Rangghran, Adam Puche, Gary Fiskum
Many victims of blast-induced traumatic brain injury are occupants of military vehicles targeted by land mines. Recently improved vehicle designs protect these individuals against blast overpressure, leaving acceleration as the main force potentially responsible for brain injury. We recently developed a unique rat model of under-vehicle blast-induced hyperacceleration where exposure to acceleration as low as 50G acceleration force results in histopathological evidence of diffuse axonal injury and astrocyte activation, with no evidence of neuronal cell death...
December 3, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27921996/the-cns-connectome-of-a-tadpole-larva-of-ciona-intestinalis-l-highlights-sidedness-in-the-brain-of-a-chordate-sibling
#7
Kerrianne Ryan, Zhiyuan Lu, Ian A Meinertzhagen
Left-right asymmetries in brains are usually minor or cryptic. We report brain asymmetries in the tiny, dorsal tubular nervous system of the ascidian tadpole larva, Ciona intestinalis. Chordate in body plan and development, the larva provides an outstanding example of brain asymmetry. Although early neural development is well studied, detailed cellular organization of the swimming larva's CNS remains unreported. Using serial-section EM we document the synaptic connectome of the larva's 177 CNS neurons. These formed 6618 synapses including 1772 neuromuscular junctions, augmented by 1206 gap junctions...
December 6, 2016: ELife
https://www.readbyqxmd.com/read/27920282/nmda-receptor-encephalitis-and-other-antibody-mediated-disorders-of-the-synapse-the-2016-cotzias-lecture
#8
Josep Dalmau
Investigations during the last 10 years have revealed a group of disorders mediated by antibodies against ion channels and synaptic receptors, which cause both neurologic and psychiatric symptoms. In this review, I discuss the process of discovery and immunologic triggers of these disorders, and use anti-NMDA receptor encephalitis to emphasize the importance of understanding the underlying physiopathologic mechanisms in those diseases. A better knowledge of these mechanisms reveals points of convergence with other disorders (e...
December 6, 2016: Neurology
https://www.readbyqxmd.com/read/27920150/heterotrimeric-kinesin-2-together-with-kinesin-1-steers-vesicular-acetylcholinesterase-movements-toward-the-synapse
#9
Anuttama Kulkarni, Yasmin Khan, Krishanu Ray
Acetylcholinesterase (AChE), which is implicated in the pathophysiology of neurological disorders, is distributed along the axon and enriched at the presynaptic basal lamina. It hydrolyses the neurotransmitter acetylcholine, which inhibits synaptic transmission. Aberrant AChE activity and ectopic axonal accumulation of the enzyme are associated with neurodegenerative disorders, such as Alzheimer's disease. The molecular mechanism that underlies AChE transport is still unclear. Here, we show that expression of Drosophila AChE tagged with photoactivable green fluorescent protein and m-Cherry (GPAC) in cholinergic neurons compensates for the RNA interference-mediated knockdown of endogenous AChE activity...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27920147/accumbens-nnos-interneurons-regulate-cocaine-relapse
#10
Alexander C W Smith, Michael D Scofield, Jasper A Heinsbroek, Cassandra D Gipson, Daniela Neuhofer, Doug J Roberts-Wolfe, Sade Spencer, Neringa M Stankeviciute, Rachel Smith, Nicholas P Allen, Melissa R Lorang, William C Griffin, Heather A Boger, Peter W Kalivas
: Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced relapse is correlated with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses on medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore), and requires spillover of glutamate from prefrontal cortical afferents. We used a rodent self-administration/reinstatement model of relapse to show that cue-induced t-SP and reinstated cocaine-seeking result from glutamate spillover initiating a metabotropic glutamate receptor 5 (mGluR5)-dependent increase in nitric oxide (NO) production...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27920126/postnatal-activation-of-tlr4-in-astrocytes-promotes-excitatory-synaptogenesis-in-hippocampal-neurons
#11
Yi Shen, Huaping Qin, Juan Chen, Lingyan Mou, Yang He, Yixiu Yan, Hang Zhou, Ya Lv, Zhong Chen, Junlu Wang, Yu-Dong Zhou
Astrocytes are critical in synapse development, and their dysfunction in crucial developmental stages leads to serious neurodevelopmental diseases, including seizures and epilepsy. Immune challenges not only affect brain development, but also promote seizure generation and epileptogenesis, implying immune activation is one of the key factors linking seizures and epilepsy to abnormal brain development. In this study, we report that activating astrocytes by systemic lipopolysaccharide (LPS) challenges in the second postnatal week promotes excitatory synapse development, leading to enhanced seizure susceptibility in mice...
December 5, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27917477/the-synaptic-vesicle-protein-sv31-assembles-into-a-dimer-and-transports-zn-2
#12
Lisa Waberer, Erik Henrich, Oliver Peetz, Nina Morgner, Volker Dötsch, Frank Bernhard, Walter Volknandt
The integral synaptic vesicle protein SV31 has been shown to bind divalent cations. Here, we demonstrate that SV31 protein synthesized within a cell-free system binds Zn(2+) and to a lower extent Ni(2+) and Cu(2+) ions. Expression with Zn(2+) stabilized the protein and increased solubility. SV31 was preferentially monomeric in detergent and revealed specific binding of Zn(2+) . When co-translationally inserted into defined nanodisc bilayers, SV31 assembled into dimeric complexes, resulting in increased binding of Zn(2+) ...
November 5, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27917469/association-of-dysfunctional-synapse-defective-1-syde1-with-restricted-fetal-growth-syde1-regulates-placental-cell-migration-and-invasion
#13
Hsiao-Fan Lo, Ching-Yen Tsai, Chie-Pein Chen, Liang-Jie Wang, Yun-Shien Lee, Chia-Yu Chen, Chung-Tiang Liang, Mei-Leng Cheong, Hungwen Chen
The transcription factor glial cells missing 1 (GCM1) regulates trophoblast differentiation and function during placentation. Decreased GCM1 expression is associated with preeclampsia, suggesting that abnormal expression of GCM1 target genes may contribute to the pathogenesis of pregnancy complications. Here we identified a novel GCM1 target gene, synapse defective 1 (SYDE1), which encodes a RhoGAP that is highly expressed in human placenta, and demonstrated that SYDE1 promotes cytoskeletal remodelling and cell migration and invasion...
December 5, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27917108/structural-and-functional-consequences-of-connexin-36-cx36-interaction-with-calmodulin
#14
Ryan C F Siu, Ekaterina Smirnova, Cherie A Brown, Christiane Zoidl, David C Spray, Logan W Donaldson, Georg Zoidl
Functional plasticity of neuronal gap junctions involves the interaction of the neuronal connexin36 with calcium/calmodulin-dependent kinase II (CaMKII). The important relationship between Cx36 and CaMKII must also be considered in the context of another protein partner, Ca(2+) loaded calmodulin, binding an overlapping site in the carboxy-terminus of Cx36. We demonstrate that CaM and CaMKII binding to Cx36 is calcium-dependent, with Cx36 able to engage with CaM outside of the gap junction plaque. Furthermore, Ca(2+) loaded calmodulin activates Cx36 channels, which is different to other connexins...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27916698/cellular-mechanisms-of-noise-induced-hearing-loss
#15
Arwa Kurabi, Elizabeth M Keithley, Gary D Housley, Allen F Ryan, Ann C-Y Wong
Exposure to intense sound or noise can result in purely temporary threshold shift (TTS), or leave a residual permanent threshold shift (PTS) along with alterations in growth functions of auditory nerve output. Recent research has revealed a number of mechanisms that contribute to noise-induced hearing loss (NIHL). The principle cause of NIHL is damage to cochlear hair cells and associated synaptopathy. Contributions to TTS include reversible damage to hair cell (HC) stereocilia or synapses, while moderate TTS reflects protective purinergic hearing adaptation...
December 1, 2016: Hearing Research
https://www.readbyqxmd.com/read/27916092/-distribution-of-postsynaptic-density-protein-95-psd95-and-synaptophysin-during-neuronal-maturation
#16
Jixia Chai, Yuanyuan Wang, Huihui Li, Wenxin He, Weiyan Zou, Yanmei Zhou, Xiaodong Hu, Qiang Chai
Objective To investigate the expressions of postsynaptic density protein 95 (PSD95) and synaptophysin (SYP) in primary culture of neurons at different times. Methods The expressions of PSD95 and SYP were detected using immunofluorescence technique in primary culture of cerebral cortical neurons at 3 days in vitro (3DIV), 7DIV and 14DIV. Results PSD95 was mainly distributed in the cell body at 3DIV, in the cell body, protuberance end and branch of neurons at 7DIV, and in the cell body as well as protuberance with a stippled pattern at 14DIV...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27914796/design-and-synthesis-of-new-piperidone-grafted-acetylcholinesterase-inhibitors
#17
Alireza Basiri, Michelle Xiao, Alec McCarthy, Debashis Dutta, Siddappa N Byrareddy, Martin Conda-Sheridan
Alzheimer's disease (AD) is a neurodegenerative disorder affecting 35million people worldwide. A common strategy to improve the well-being of AD patients consists on the inhibition of acetylcholinesterase with the concomitant increase of the neurotransmitter acetylcholine at cholinergic synapses. Two series of unreported N-benzylpiperidines 5(a-h) and thiazolopyrimidines 9(a-q) molecules were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activities. Among the newly synthesized compounds, 5h, 9h, 9j, and 9p displayed higher AChE enzyme inhibitory activities than the standard drug, galantamine, with IC50 values of 0...
November 24, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27914199/filamin-a-synaptic-organizer-in-drosophila-determines-glutamate-receptor-composition-and-membrane-growth
#18
GaYoung Lee, Thomas L Schwarz
Filamin is a scaffolding protein that functions in many cells as an actin-crosslinker. FLN90, an isoform of the Drosophila ortholog Filamin/cheerio that lacks the actin-binding domain, is here shown to govern the growth of postsynaptic membrane folds and the composition of glutamate receptor clusters at the larval neuromuscular junction. Genetic and biochemical analyses revealed that FLN90 is present surrounding synaptic boutons. FLN90 is required in the muscle for localization of the kinase dPak and, downstream of dPak, for localization of the GTPase Ral and the exocyst complex to this region...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27913592/complexin-mutants-reveal-partial-segregation-between-recycling-pathways-that-drive-evoked-and-spontaneous-neurotransmission
#19
Nadezhda Sabeva, Richard W Cho, Alexander Vasin, Agustin Gonzalez, J Troy Littleton, Maria Bykhovskaia
: Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals. It is still unclear whether vesicles that fuse spontaneously or following evoked release share similar recycling mechanisms. Genetic deletion of the SNARE-binding protein complexin dramatically increases spontaneous fusion, with the protein serving as the synaptic vesicle fusion clamp at Drosophila synapses...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27913590/control-of-spike-transfer-at-hippocampal-mossy-fiber-synapses-in-vivo-by-gabaa-and-gabab-receptor-mediated-inhibition
#20
Stefano Zucca, Marilena Griguoli, Meryl Malézieux, Noëlle Grosjean, Mario Carta, Christophe Mulle
: Despite extensive studies in hippocampal slices and incentive from computational theories, the synaptic mechanisms underlying information transfer at mossy fiber (mf) connections between the dentate gyrus (DG) and CA3 neurons in vivo are still elusive. Here we used an optogenetic approach in mice to selectively target and control the activity of DG granule cells (GCs) while performing whole cell and juxtacellular recordings of CA3 neurons in vivo In CA3 pyramidal cells (PCs), mf-CA3 synaptic responses consisted predominantly of an inhibitory postsynaptic potential (IPSP) at low stimulation frequency (0...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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