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https://www.readbyqxmd.com/read/28317880/antidromic-rectifying-gap-junctions-amplify-chemical-transmission-at-functionally-mixed-electrical-chemical-synapses
#1
Ping Liu, Bojun Chen, Roger Mailler, Zhao-Wen Wang
Neurons communicate through chemical synapses and electrical synapses (gap junctions). Although these two types of synapses often coexist between neurons, little is known about whether they interact, and whether any interactions between them are important to controlling synaptic strength and circuit functions. By studying chemical and electrical synapses between premotor interneurons (AVA) and downstream motor neurons (A-MNs) in the Caenorhabditis elegans escape circuit, we found that disrupting either the chemical or electrical synapses causes defective escape response...
March 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28295002/-ultrastructural-characteristics-of-gap-junctions-in-human-glial-brain-tumors
#2
E Yu Kirichenko, A F Savchenko, D V Kozachenko, A E Matsionis, A K Logvinov
AIM: to conduct an electron microscopic study of intercellular communication in the samples of gemistocytic astrocytoma, oligodendroglioma, and glioblastoma. MATERIAL AND METHODS: Surgically resected tumor tissue fragments were fixed in 2.5% glutaraldehyde solution, afterfixed in 1% OsO4 solution, dehydrated, and embedded in epoxy resin. Ultrathin sections were examined using a Jem 1011 electron microscope (Jeol, Japan). RESULTS: Solitary and closely spaced gap junctions (GJs) formed by the thin processes that have the ultrastructure of an astroglial processes were identified in the astrocytoma samples...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28286129/fret-based-sensors-unravel-activation-and-allosteric-modulation-of-the-gabab-receptor
#3
Nathalie Lecat-Guillet, Carine Monnier, Xavier Rovira, Julie Kniazeff, Laurent Lamarque, Jurriaan M Zwier, Eric Trinquet, Jean-Philippe Pin, Philippe Rondard
The main inhibitory neurotransmitter, γ-aminobutyric acid (GABA), modulates many synapses by activating the G protein-coupled receptor GABAB, which is a target for various therapeutic applications. It is an obligatory heterodimer made of GB1 and GB2 that can be regulated by positive allosteric modulators (PAMs). The molecular mechanism of activation of the GABAB receptor remains poorly understood. Here, we have developed FRET-based conformational GABAB sensors compatible with high-throughput screening. We identified conformational changes occurring within the extracellular and transmembrane domains upon receptor activation, which are smaller than those observed in the related metabotropic glutamate receptors...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28267198/serotonergic-transmission-at-merkel-discs-modulation-by-exogenously-applied-chemical-messengers-and-involvement-of-ih-currents
#4
Weipang Chang, Hirosato Kanda, Ryo Ikeda, Jennifer Ling, Jianguo G Gu
The Merkel disc is a main type of tactile end organ consisting of Merkel cells and Aβ-afferent endings that responds to tactile stimulation with slowly adapting type 1 (SA1) afferent impulses. Our recent study has shown that Merkel discs in whisker hair follicles are serotonergic synapses using endogenous serotonin to transmit tactile signals from Merkel cells to Aβ-afferent endings. In the present study, we hypothesize that tactile sensitivity of Merkel discs can be modulated by chemical messengers. We tested this hypothesis by determining whether and how SA1 responses of mouse whisker hair follicles may be affected by exogenously applied chemical messengers...
March 7, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28265099/neonatal-cx26-removal-impairs-neocortical-development-and-leads-to-elevated-anxiety
#5
Xin Su, Jing-Jing Chen, Lin-Yun Liu, Qian Huang, Li-Zhao Zhang, Xiao-Yang Li, Xiang-Nan He, Wenlian Lu, Shan Sun, Huawei Li, Yong-Chun Yu
Electrical coupling between excitatory neurons in the neocortex is developmentally regulated. It is initially prominent but eliminated at later developmental stages when chemical synapses emerge. However, it remains largely unclear whether early electrical coupling networks broadly contribute to neocortical circuit formation and animal behavior. Here, we report that neonatal electrical coupling between neocortical excitatory neurons is critical for proper neuronal development, synapse formation, and animal behavior...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28260370/mimicking-neurotransmitter-release-in-chemical-synapses-via-hysteresis-engineering-in-mos2-transistors
#6
Andrew Joseph Arnold, Ali Razavieh, Joseph R Nasr, Daniel S Schulman, Chad M Eichfeld, Saptarshi Das
Neurotransmitter release in chemical synapses is fundamental to diverse brain functions like motor action, learning, cognition, emotion, perception and consciousness. Moreover, improper functioning or abnormal release of neurotransmitter is associated with numerous neurological disorders like epilepsy, sclerosis, schizophrenia, Alzheimer's disease and Parkinson's disease. We have utilized hysteresis engineering in a back gated MoS2 field effect transistor (FETs) in order to mimic such neurotransmitter release dynamics in chemical synapses...
March 4, 2017: ACS Nano
https://www.readbyqxmd.com/read/28238793/differential-maturation-of-the-two-regulated-secretory-pathways-in-human-ipsc-derived-neurons
#7
Javier Emperador Melero, Aishwarya G Nadadhur, Desiree Schut, Jan V Weering, Vivi M Heine, Ruud F Toonen, Matthijs Verhage
Neurons communicate by regulated secretion of chemical signals from synaptic vesicles (SVs) and dense-core vesicles (DCVs). Here, we investigated the maturation of these two secretory pathways in micro-networks of human iPSC-derived neurons. These micro-networks abundantly expressed endogenous SV and DCV markers, including neuropeptides. DCV transport was microtubule dependent, preferentially anterograde in axons, and 2-fold faster in axons than in dendrites. SV and DCV secretion were strictly Ca(2+) and SNARE dependent...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28228251/spatial-and-temporal-regulation-of-receptor-endocytosis-in-neuronal-dendrites-revealed-by-imaging-of-single-vesicle-formation
#8
Morgane Rosendale, Damien Jullié, Daniel Choquet, David Perrais
Endocytosis in neuronal dendrites is known to play a critical role in synaptic transmission and plasticity such as long-term depression (LTD). However, the inability to detect endocytosis directly in living neurons has hampered studies of its dynamics and regulation. Here, we visualized the formation of individual endocytic vesicles containing pHluorin-tagged receptors with high temporal resolution in the dendrites of cultured hippocampal neurons. We show that transferrin receptors (TfRs) are constitutively internalized at optically static clathrin-coated structures...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28214749/impairment-in-the-mesohippocampal-dopamine-circuit-following-exposure-to-the-brominated-flame-retardant-hbcdd
#9
Camille Pham-Lake, Elizabeth B Aronoff, Chad R Camp, Aimee Vester, Sam J Peters, W Michael Caudle
Many chemicals have been used to increase the safety of consumer products by reducing their flammability and risk for ignition. Recent focus on brominated flame retardants, such as polybrominated diphenyl ethers (PBDEs) has shown them to contribute to neurobehavioral deficits in children, including learning and memory. As the manufacture and use of PBDEs have been reduced, replacement chemicals, such as hexabromocyclododecane (HBCDD) have been substituted. Our current study evaluated the neurotoxicity of HBCDD, concentrating on dopaminergic innervation to the hippocampus...
March 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28213516/rapid-regulation-of-sialidase-activity-in-response-to-neural-activity-and-sialic-acid-removal-during-memory-processing-in-rat-hippocampus
#10
Akira Minami, Yuko Meguro, Sayaka Ishibashi, Ami Ishii, Mako Shiratori, Saki Sai, Yuuki Horii, Hirotaka Shimizu, Hokuto Fukumoto, Sumika Shinba, Risa Taguchi, Tadanobu Takahashi, Tadamune Otsubo, Kiyoshi Ikeda, Takashi Suzuki
Sialidase cleaves sialic acids on the extracellular cell surface as well as inside the cell, and is necessary for normal long-term potentiation (LTP) at MF-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4MU-Neu5Ac or X-Neu5Ac and FRV LB was increased by high K(+)-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDARs or NMDARs...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28209589/second-generation-drosophila-chemical-tags-sensitivity-versatility-and-speed
#11
Ben Sutcliffe, Julian Ng, Thomas O Auer, Mathias Pasche, Richard Benton, Gregory S X E Jefferis, Sebastian Cachero
Labeling and visualizing cells and subcellular structures within thick tissues, whole organs and even intact animals is key to studying biological processes. This is particularly true for studies of neural circuits where neurons form submicron synapses but have arbors that may span millimeters in length. Traditionally, labeling is achieved by immunofluorescence; however diffusion of antibody molecules (>100 kDa) is slow and often results in uneven labeling with very poor penetration into the centre of thick specimens; these limitations can be partially addressed by extending staining protocols to over a week (Drosophila brain) and months (mice)...
February 16, 2017: Genetics
https://www.readbyqxmd.com/read/28202712/ribeye-b-domain-binds-to-lipid-components-of-synaptic-vesicles-in-an-nad-h-dependent-redox-sensitive-manner
#12
Karin Schwarz, Frank Schmitz
Synaptic ribbons are needed for fast and continuous exocytosis in ribbon synapses. RIBEYE is a main protein component of synaptic ribbons and is necessary to build the synaptic ribbon. RIBEYE consists of a unique A-domain and a carboxyterminal B-domain, which binds NAD(H). Within the presynaptic terminal, the synaptic ribbons are in physical contact with large numbers of synaptic vesicle (SV)s. How this physical contact between ribbons and synaptic vesicles is established at a molecular level is not well understood...
March 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28167663/fusion-pores-and-their-control-of-neurotransmitter-and-hormone-release
#13
REVIEW
Che-Wei Chang, Chung-Wei Chiang, Meyer B Jackson
Ca(2+)-triggered exocytosis functions broadly in the secretion of chemical signals, enabling neurons to release neurotransmitters and endocrine cells to release hormones. The biological demands on this process can vary enormously. Although synapses often release neurotransmitter in a small fraction of a millisecond, hormone release can be orders of magnitude slower. Vesicles usually contain multiple signaling molecules that can be released selectively and conditionally. Cells are able to control the speed, concentration profile, and content selectivity of release by tuning and tailoring exocytosis to meet different biological demands...
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28163671/drive-the-car-go-s-new-modalities-to-control-cargo-trafficking-in-live-cells
#14
REVIEW
Payel Mondal, John S Khamo, Vishnu V Krishnamurthy, Qi Cai, Kai Zhang
Synaptic transmission is a fundamental molecular process underlying learning and memory. Successful synaptic transmission involves coupled interaction between electrical signals (action potentials) and chemical signals (neurotransmitters). Defective synaptic transmission has been reported in a variety of neurological disorders such as Autism and Alzheimer's disease. A large variety of macromolecules and organelles are enriched near functional synapses. Although a portion of macromolecules can be produced locally at the synapse, a large number of synaptic components especially the membrane-bound receptors and peptide neurotransmitters require active transport machinery to reach their sites of action...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28148726/synchronous-infra-slow-bursting-in-the-mouse-accessory-olfactory-bulb-emerge-from-interplay-between-intrinsic-neuronal-dynamics-and-network-connectivity
#15
Asaph Zylbertal, Yosef Yarom, Shlomo Wagner
Rhythmic neuronal activity of multiple frequency bands has been described in many brain areas and attributed to numerous brain functions. Among these, little is known about the mechanism and role of infra-slow oscillations, which have been recently demonstrated in the mouse accessory olfactory bulb (AOB). Along with prolonged responses to stimuli and distinct network connectivity, they inexplicably affect the AOB processing of social relevant stimuli. Here we show that assemblies of AOB mitral cells are synchronized by lateral interactions through chemical and electrical synapses...
February 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28143932/dissection-of-neuronal-gap-junction-circuits-that-regulate-social-behavior-in-caenorhabditis-elegans
#16
Heeun Jang, Sagi Levy, Steven W Flavell, Fanny Mende, Richard Latham, Manuel Zimmer, Cornelia I Bargmann
A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9-containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9-based gap junctions with dominant-negative unc-1 transgenes...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28125716/numerical-simulations-reveal-randomness-of-cu-ii-induced-a%C3%AE-peptide-dimerization-under-conditions-present-in-glutamatergic-synapses
#17
Wojciech Goch, Wojciech Bal
The interactions between the Aβ1-40 molecules species and the copper ions (Cu(II)) were intensively investigated due to their potential role in the development of the Alzheimer Disease (AD). The rate and the mechanism of the Cu(II)-Aβ complexes formation determines the aggregation pathway of the Aβ species, starting from smaller but more cytotoxic oligomers and ending up in large Aβ plaques, being the main hallmark of the AD. In our study we exploit the existing knowledge on the Cu(II)-Aβ interactions and create the theoretical model of the initial phase of the copper- driven Aβ aggregation mechanism...
2017: PloS One
https://www.readbyqxmd.com/read/28119500/interference-of-the-complex-between-ncs-1-and-ric8a-with-phenothiazines-regulates-synaptic-function-and-is-an-approach-for-fragile-x-syndrome
#18
Alicia Mansilla, Antonio Chaves-Sanjuan, Nuria E Campillo, Ourania Semelidou, Loreto Martínez-González, Lourdes Infantes, Juana María González-Rubio, Carmen Gil, Santiago Conde, Efthimios M C Skoulakis, Alberto Ferrús, Ana Martínez, María José Sánchez-Barrena
The protein complex formed by the Ca(2+) sensor neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor protein Ric8a coregulates synapse number and probability of neurotransmitter release, emerging as a potential therapeutic target for diseases affecting synapses, such as fragile X syndrome (FXS), the most common heritable autism disorder. Using crystallographic data and the virtual screening of a chemical library, we identified a set of heterocyclic small molecules as potential inhibitors of the NCS-1/Ric8a interaction...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28117022/acetylcholinesterase-a-primary-target-for-drugs-and-insecticides
#19
Sunita Thapa, Min Lv, Hui Xu
Acetylcholinesterase is a serine hydrolase that terminates the action of the neurotransmitter acetylcholine by hydrolyzing it into acetic acid and choline. The molecule, having an ellipsoidal structure, possesses three binding sites; active site (with catalytic anionic and esteratic subsites), aromatic gorge and peripheral anionic site, where the inhibiting compounds interact. The acetylcholinesterase inhibitors bind to the molecule and interfere with the breakdown of acetylcholine leading to the deposition of acetylcholine in the nerve synapses and causing disrupted neurotransmission...
January 20, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28065648/taok2-kinase-mediates-psd95-stability-and-dendritic-spine-maturation-through-septin7-phosphorylation
#20
Smita Yadav, Juan A Oses-Prieto, Christian J Peters, Jing Zhou, Samuel J Pleasure, Alma L Burlingame, Lily Y Jan, Yuh-Nung Jan
Abnormalities in dendritic spines are manifestations of several neurodevelopmental and psychiatric diseases. TAOK2 is one of the genes in the 16p11.2 locus, copy number variations of which are associated with autism and schizophrenia. Here, we show that the kinase activity of the serine/threonine kinase encoded by TAOK2 is required for spine maturation. TAOK2 depletion results in unstable dendritic protrusions, mislocalized shaft-synapses, and loss of compartmentalization of NMDA receptor-mediated calcium influx...
January 18, 2017: Neuron
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