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https://www.readbyqxmd.com/read/28209589/second-generation-drosophila-chemical-tags-sensitivity-versatility-and-speed
#1
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
#2
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 necessary to build the synaptic ribbon. RIBEYE consists of a unique A-domain and a carboxyterminal B-domain that binds NAD(H). Within the presynaptic terminal, the synaptic ribbons are in physical contact with large numbers of synaptic vesicles. How this physical contact between ribbons and vesicles is established at a molecular level is not well understood. In the present study, we demonstrate that the RIBEYE(B)-domain can directly interact with lipid components of synaptic vesicles using two different sedimentation assays with liposomes of defined chemical composition...
February 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28167663/fusion-pores-and-their-control-of-neurotransmitter-and-hormone-release
#3
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...
February 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
#4
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
#5
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
#6
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...
January 31, 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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28039376/a-mammalian-retinal-ganglion-cell-implements-a-neuronal-computation-that-maximizes-the-snr-of-its-postsynaptic-currents
#11
Jan Homann, Michael A Freed
Neurons perform computations by integrating excitatory and inhibitory synaptic inputs. Yet, it is rarely understood what computation is being performed, or how much excitation or inhibition this computation requires. Here we present evidence for a neuronal computation that maximizes the signal-to-noise power ratio (SNR). We recorded from OFF delta retinal ganglion cells in the guinea pig retina and monitored synaptic currents that were evoked by visual stimulation (flashing dark spots). These synaptic currents were mediated by a decrease in an outward current from inhibitory synapses (disinhibition) combined with an increase in an inward current from excitatory synapses...
February 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28030363/new-dimensions-of-connectomics-and-network-plasticity-in-the-central-nervous-system
#12
Diego Guidolin, Manuela Marcoli, Guido Maura, Luigi F Agnati
Cellular network architecture plays a crucial role as the structural substrate for the brain functions. Therefore, it represents the main rationale for the emerging field of connectomics, defined as the comprehensive study of all aspects of central nervous system connectivity. Accordingly, in the present paper the main emphasis will be on the communication processes in the brain, namely wiring transmission (WT), i.e. the mapping of the communication channels made by cell components such as axons and synapses, and volume transmission (VT), i...
February 1, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/27997993/longitudinal-imaging-reveals-subhippocampal-dynamics-in-glutamate-levels-associated-with-histopathologic-events-in-a-mouse-model-of-tauopathy-and-healthy-mice
#13
Rachelle Crescenzi, Catherine DeBrosse, Ravi P R Nanga, Matthew D Byrne, Guruprasad Krishnamoorthy, Kevin D'Aquilla, Hari Nath, Knashawn H Morales, Michiyo Iba, Hari Hariharan, Virginia M Y Lee, John A Detre, Ravinder Reddy
Tauopathies are neurodegenerative disorders characterized by abnormal intracellular aggregates of tau protein, and include Alzheimer's disease, corticobasal degeneration, frontotemporal dementia, and traumatic brain injury. Glutamate metabolism is altered in neurodegenerative disorders manifesting in higher or lower concentrations of glutamate, its transporters or receptors. Previously, glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) demonstrated that glutamate levels are reduced in regions of synapse loss in the hippocampus of a mouse model of late-stage tauopathy...
March 2017: Hippocampus
https://www.readbyqxmd.com/read/27988303/anticonvulsant-efficacy-of-antihistamine-cyproheptadine-in-rats-exposed-to-the-chemical-warfare-nerve-agent-soman
#14
Jennifer L Winkler, Jacob W Skovira, Robert K Kan
Organophosphate compounds, such as soman and sarin, are highly toxic chemical warfare nerve agents that cause a build-up of acetylcholine in synapses and neuromuscular junctions. Current therapies aim to prevent seizures and protect against brain injury following exposure. The present study was designed to evaluate the effectiveness of the antihistamine cyproheptadine in improving survival and controlling seizures in rats exposed to soman. Rats were pretreated with the oxime reactivator HI-6 (125mg/kg, ip) 30min prior to soman exposure (225μg/kg, sc) and then treated with atropine methylnitrate (AMN, 2...
December 14, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/27986956/single-molecule-analysis-of-%C3%AF-c31-integrase-mediated-site-specific-recombination-by-tethered-particle-motion
#15
Hsiu-Fang Fan, Tao-Shih Hsieh, Chien-Hui Ma, Makkuni Jayaram
Serine and tyrosine site-specific recombinases (SRs and YRs, respectively) provide templates for understanding the chemical mechanisms and conformational dynamics of strand cleavage/exchange between DNA partners. Current evidence suggests a rather intriguing mechanism for serine recombination, in which one half of the cleaved synaptic complex undergoes a 180° rotation relative to the other. The 'small' and 'large' SRs contain a compact amino-terminal catalytic domain, but differ conspicuously in their carboxyl-terminal domains...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27986924/pharmacological-rescue-of-long-term-potentiation-in-alzheimer-diseased-synapses
#16
G Aleph Prieto, Brian H Trieu, Cindy T Dang, Tina Bilousova, Karen H Gylys, Nicole C Berchtold, Gary Lynch, Carl W Cotman
: Long-term potentiation (LTP) is an activity-dependent and persistent increase in synaptic transmission. Currently available techniques to measure LTP are time-intensive and require highly specialized expertise and equipment, and thus are not well-suited for screening of multiple candidate treatments even in animal models. To expand and facilitate the analysis of LTP, here we use a flow cytometry-based method to track chemically-induced LTP by detecting surface AMPA receptors in isolated synaptosomes (Fluorescence Analysis of Single-Synapse Long-Term Potentiation, FASS-LTP)...
December 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27958355/chimera-states-in-uncoupled-neurons-induced-by-a-multilayer-structure
#17
Soumen Majhi, Matjaž Perc, Dibakar Ghosh
Spatial coexistence of coherent and incoherent dynamics in network of coupled oscillators is called a chimera state. We study such chimera states in a network of neurons without any direct interactions but connected through another medium of neurons, forming a multilayer structure. The upper layer is thus made up of uncoupled neurons and the lower layer plays the role of a medium through which the neurons in the upper layer share information among each other. Hindmarsh-Rose neurons with square wave bursting dynamics are considered as nodes in both layers...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27943184/biochemical-purification-of-binding-partners-of-synaptic-scaffold-proteins
#18
Bekir Altas, Olaf Jahn, Hiroshi Kawabe
The chemical synapse displays specialized intercellular adhesion between pre- and potsynaptic plasma membranes mediated by synaptic cell adhesion proteins. In this asymmetric cell adhesion, pre- and postsynapses have their own unique functions; the presynaptic terminal releases neurotransmitter, which diffuses through the synaptic cleft and is received by receptors accumulated at the postsynapse. Such distinct modes of actions of pre- and postsynapses in synaptic neurotransmission are the rate-limiting factors in signal processing in the brain, and thus protein-protein interactions within the pre- and postsynaptic scaffold are of particular importance for brain function by regulating the pre- and postsynaptic function...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27917477/the-synaptic-vesicle-protein-sv31-assembles-into-a-dimer-and-transports-zn-2
#19
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/27911759/neurotransmitter-release-can-be-stabilized-by-a-mechanism-that-prevents-voltage-changes-near-the-end-of-action-potentials-from-affecting-calcium-currents
#20
Stephen G Clarke, Matthew S Scarnati, Kenneth G Paradiso
: At chemical synapses, presynaptic action potentials (APs) activate voltage-gated calcium channels, allowing calcium to enter and trigger neurotransmitter release. The duration, peak amplitude, and shape of the AP falling phase alter calcium entry, which can affect neurotransmitter release significantly. In many neurons, APs do not immediately return to the resting potential, but instead exhibit a period of depolarization or hyperpolarization referred to as an afterpotential. We hypothesized that presynaptic afterpotentials should alter neurotransmitter release by affecting the electrical driving force for calcium entry and calcium channel gating...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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