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Synaptic transmission

Isabella Maiellaro, Martin J Lohse, Robert J Kittel, Davide Calebiro
The second messenger cyclic AMP (cAMP) plays an important role in synaptic plasticity. Although there is evidence for local control of synaptic transmission and plasticity, it is less clear whether a similar spatial confinement of cAMP signaling exists. Here, we suggest a possible biophysical basis for the site-specific regulation of synaptic plasticity by cAMP, a highly diffusible small molecule that transforms the physiology of synapses in a local and specific manner. By exploiting the octopaminergic system of Drosophila, which mediates structural synaptic plasticity via a cAMP-dependent pathway, we demonstrate the existence of local cAMP signaling compartments of micrometer dimensions within single motor neurons...
October 25, 2016: Cell Reports
Song Cai, Chuwen Ling, Jun Lu, Songwei Duan, Yingzhao Wang, Huining Zhu, Ruibang Lin, Liang Chen, Xingchang Pan, Muyi Cai, Huaiyu Gu
A primary pathogeny of epilepsy is excessive activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs). To find potential molecules to inhibit AMPARs, high-throughput screening was performed in a library of tetrapeptides in silico. Computational results suggest that some tetrapeptides bind stably to the AMPAR. We aligned these sequences of tetrapeptide candidates with those from in vitro digestion of the trout skin protein. Among salmon-derived products, Glu-Gly-Ala-Arg (EGAR) showed a high biological affinity toward AMPAR when tested in silico...
October 25, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Seika Takayanagi-Kiya, Keming Zhou, Yishi Jin
Presynaptic ligand-gated ion channels (LGICs) have long been proposed to affect neurotransmitter release and to tune neural circuit activity. However, the understanding of their in vivo physiological action remains limited, partly due to the complexity in channel types and scarcity of genetic models. Here we report that C. elegans LGC-46, a member of the Cys-loop acetylcholine (ACh)-gated chloride (ACC) channel family, localizes to presynaptic terminals of cholinergic motor neurons and regulates synaptic vesicle (SV) release kinetics upon evoked release of acetylcholine...
October 26, 2016: ELife
Martina Landini, Ivan Merelli, M Elisabetta Raggi, Nadia Galluccio, Francesca Ciceri, Arianna Bonfanti, Serena Camposeo, Angelo Massagli, Laura Villa, Erika Salvi, Daniele Cusi, Massimo Molteni, Luciano Milanesi, Anna Marabotti, Alessandra Mezzelani
Since involved in synaptic transmission and located on X-chromosome, neuroligins 3 and 4X have been studied as good positional and functional candidate genes for autism spectrum disorder pathogenesis, although contradictory results have been reported. Here, we performed a case-control study to assess the association between noncoding genetic variants in NLGN3 and NLGN4X genes and autism, in an Italian cohort of 202 autistic children analyzed by high-resolution melting. The results were first compared with data from 379 European healthy controls (1000 Genomes Project) and then with those from 1061 Italian controls genotyped by Illumina single nucleotide polymorphism (SNP) array 1M-duo...
October 22, 2016: International Journal of Molecular Sciences
Yu-Hang Zhang, Chen Chu, Shaopeng Wang, Lei Chen, Jing Lu, XiangYin Kong, Tao Huang, HaiPeng Li, Yu-Dong Cai
A drug's biological half-life is defined as the time required for the human body to metabolize or eliminate 50% of the initial drug dosage. Correctly measuring the half-life of a given drug is helpful for the safe and accurate usage of the drug. In this study, we investigated which gene ontology (GO) terms and biological pathways were highly related to the determination of drug half-life. The investigated drugs, with known half-lives, were analyzed based on their enrichment scores for associated GO terms and KEGG pathways...
2016: PloS One
Adam J Harrington, Aram Raissi, Kacey Rajkovich, Stefano Berto, Jaswinder Kumar, Gemma Molinaro, Jonathan Raduazzo, Yuhong Guo, Kris Loerwald, Genevieve Konopka, Kimberly M Huber, Christopher W Cowan
Numerous genetic variants associated with MEF2C are linked to autism, intellectual disability (ID) and schizophrenia (SCZ) - a heterogeneous collection of neurodevelopmental disorders with unclear pathophysiology. MEF2C is highly expressed in developing cortical excitatory neurons, but its role in their development remains unclear. We show here that conditional embryonic deletion of Mef2c in cortical and hippocampal excitatory neurons (Emx1-lineage) produces a dramatic reduction in cortical network activity in vivo, due in part to a dramatic increase in inhibitory and a decrease in excitatory synaptic transmission...
October 25, 2016: ELife
Doris Koesling, Evanthia Mergia, Michael Russwurm
NO-sensitive guanylyl cyclase (NO-GC) acts as the receptor for nitric oxide and by the increase in cGMP executes most of the NO effects in the cardiovascular and neuronal system. Two isoforms of NO-GC exist whose existence has not been paid much attention to probably because they reveal comparable regulatory and catalytic properties and therefore cannot be differentiated in vivo. Analysis of mice in which either one of the isoforms has been genetically deleted unequivocally establishes the coexpression of NO-GC1 and NOGC2 in any tissue tested to date with the exception of platelets...
2016: Current Medicinal Chemistry
Martina Held, Annuska Berz, Ronja Hensgen, Thomas S Muenz, Christina Scholl, Wolfgang Rössler, Uwe Homberg, Keram Pfeiffer
While the ability of honeybees to navigate relying on sky-compass information has been investigated in a large number of behavioral studies, the underlying neuronal system has so far received less attention. The sky-compass pathway has recently been described from its input region, the dorsal rim area (DRA) of the compound eye, to the anterior optic tubercle (AOTU). The aim of this study is to reveal the connection from the AOTU to the central complex (CX). For this purpose, we investigated the anatomy of large microglomerular synaptic complexes in the medial and lateral bulbs (MBUs/LBUs) of the lateral complex (LX)...
2016: Frontiers in Behavioral Neuroscience
P Tenreiro, S Rebelo, F Martins, M Santos, E D Coelho, M Almeida, A P Alves de Matos, O A B da Cruz E Silva
Synaptosomes are isolated nerve terminals. They represent an extremely attractive in vitro model system to study synaptic physiology since they preserve morphological and functional characteristics of the synapse. As such they have been used to investigate synaptic dysfunctions associated with neuropathologies like Alzheimer's disease. In the present work two simple methodologies for isolating synaptosomal-enriched fractions were compared for the first time. The starting points of both protocols were rat cortical or hippocampal homogenized tissues that underwent several differential centrifugation steps followed by a final purification of synaptosomal-enriched fractions using either a Percoll gradient or a Sucrose gradient...
October 19, 2016: Analytical Biochemistry
Yuzuki Kanda, Miho Okada, Rina Ikarashi, Eri Morioka, Takashi Kondo, Masayuki Ikeda
Clozapine (Clz) and olanzapine (Olz) are second generation (atypical) antipsychotics, used widely for treating schizophrenia and bipolar disorder. These drugs share multiple sites of actions, however their mechanisms remain incompletely understood. Here, we analyzed the effects of these drugs on primary cultures of rat cortical astrocytes and C6 glioma cells using fura-2-based Ca(2+) imaging. C6 cells, but not cortical astrocytes, express the serotonin 2A receptor subtype, which couples to phospholipase C. Clz (1μM) significantly blocked serotonin-induced Ca(2+) transients in C6 cells, consistent with known antagonistic actions of Clz...
October 18, 2016: Neuroscience Letters
Malik Nassan, Qingqin Li, Paul E Croarkin, Wenan Chen, Colin L Colby, Marin Veldic, Susan L McElroy, Gregory D Jenkins, Euijung Ryu, Julie M Cunningham, Marion Leboyer, Mark A Frye, Joanna M Biernacka
BACKGROUND: Although multiple genes have been implicated in bipolar disorder (BD), they explain only a small proportion of its heritability. Identifying additional BD risk variants may be impaired by phenotypic heterogeneity, which is usually not taken into account in genome-wide association studies (GWAS). BD with early age at onset is a more homogeneous familial form of the disorder associated with greater symptom severity. METHODS: We conducted a GWAS of early-onset BD (onset of mania/hypomania ≤19 years old) in a discovery sample of 419 cases and 1034 controls and a replication sample of 181 cases and 777 controls...
September 30, 2016: Journal of Affective Disorders
Ramón Martínez-Mármol, Bruna Barneda-Zahonero, David Soto, Rosa Maria Andrés, Elena Coccia, Xavier Gasull, Laura Planells-Ferrer, Rana S Moubarak, Eduardo Soriano, Joan X Comella
Caspases have recently emerged as key regulators of axonal pruning and degeneration and of long-term depression (LTD), a long-lasting form of synaptic plasticity. However, the mechanism underlying these functions remains unclear. In this context, XIAP has been shown to modulate these processes. The neuron-specific form of FAIM protein (FAIM-L) is a death receptor antagonist that stabilizes XIAP protein levels, thus preventing death receptor-induced neuronal apoptosis. Here we show that FAIM-L modulates synaptic transmission, prevents chemical-LTD induction in hippocampal neurons, and thwarts axon degeneration after nerve growth factor (NGF) withdrawal...
October 21, 2016: Scientific Reports
Alice Filippini, Daniela Bonini, Luca La Via, Alessandro Barbon
Glutamate receptors play a key role in excitatory synaptic transmission and plasticity in the central nervous system (CNS). Their channel properties are largely dictated by the subunit composition of tetrameric receptors. Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate channels are assembled from GluA1-4 AMPA or GluK1-5 kainate receptor subunits. However, their functional properties are highly modulated by a post-transcriptional mechanism called RNA editing. This process involves the enzymatic deamination of specific adenosines (A) into inosines (I) in pre-messenger RNA...
October 20, 2016: Molecular Neurobiology
Jessica M Meves, Binhai Zheng
In this issue of Neuron, Tedeschi et al. (2016) describe the voltage-gated calcium channel subunit alpha2delta2 as a developmental switch from axon elongation to synapse formation and transmission that doubles as a suppressor of axon regeneration, providing a molecular clue for the synaptic stabilization hypothesis of CNS regeneration failure.
October 19, 2016: Neuron
Marta Gómez-Galán, Teresa Femenía, Elin Åberg, Lisette Graae, Ann Van Eeckhaut, Ilse Smolders, Stefan Brené, Maria Lindskog
Stress, such as social isolation, is a well-known risk factor for depression, most probably in combination with predisposing genetic factors. Physical exercise on the other hand, is depicted as a wonder-treatment that makes you healthier, happier and live longer. However, the published results on the effects of exercise are ambiguous, especially when it comes to neuropsychiatric disorders. Here we combine a paradigm of social isolation with a genetic rat model of depression, the Flinders Sensitive Line (FSL), already known to have glutamatergic synaptic alterations...
2016: PloS One
Chao-Chen Lin, Hsin-Fang Hsu, Peter Jomo Walla
The fusion of two opposing membranes is essential in biological functions such as fertilization, viral entry, membrane trafficking and synaptic transmission. Before the membrane bilayers are fully connected, at some stage a hemifusion intermediate-when the outer leaflets are merged but not the inner leaflets-is formed. However, the position of hemifusion in the energy landscape and the duration of it vary and have not been fully mapped out. To date, there has not been a way to differentiate lipid mixing of the two leaflets directly in a single experiment...
October 20, 2016: Journal of Physical Chemistry. B
A Eraso-Pichot, R Larramona-Arcas, E Vicario-Orri, R Villalonga, L Pardo, E Galea, R Masgrau
Astrocytic excitability relies on cytosolic calcium increases as a key mechanism, whereby astrocytes contribute to synaptic transmission and hence learning and memory. While it is a cornerstone of neurosciences that experiences are remembered, because transmitters activate gene expression in neurons, long-term adaptive astrocyte plasticity has not been described. Here, we investigated whether the transcription factor CREB mediates adaptive plasticity-like phenomena in astrocytes. We found that activation of CREB-dependent transcription reduced the calcium responses induced by ATP, noradrenaline, or endothelin-1...
October 19, 2016: Cellular and Molecular Life Sciences: CMLS
Maksim Storozhuk, Elena Kondratskaya, Lyudmila Nikolaenko, Oleg Krishtal
Rapid acidification occurring during synaptic vesicle release can activate acid-sensing ion channels (ASICs) both on pre- and postsynaptic neurons. In the latter case, a fraction of postsynaptic current would be mediated by cation-selective acid-sensing ion channels. Additionally, in both cases, activation of acid-sensing ion channels could modulate synaptic strength by affecting transmitter release and/or sensitivity of postsynaptic receptors. To address potential involvement of acid-sensing ion channels in mediation/modulation of synaptic transmission at hippocampal GABAergic synapses, we studied effects of three structurally different blockers of acid-sensing ion channels on evoked postsynaptic currents using the patch-clamp technique...
October 19, 2016: Molecular Brain
Petra Mrozkova, Diana Spicarova, Jiri Palecek
Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors in the peripheral nerve endings are implicated in the development of increased sensitivity to mechanical and thermal stimuli, especially during inflammatory states. Both PAR2 and TRPV1 receptors are co-expressed in nociceptive dorsal root ganglion (DRG) neurons on their peripheral endings and also on presynaptic endings in the spinal cord dorsal horn. However, the modulation of nociceptive synaptic transmission in the superficial dorsal horn after activation of PAR2 and their functional coupling with TRPV1 is not clear...
2016: PloS One
Laura Contreras, Laura Ramirez, Jianhai Du, James B Hurley, Jorgina Satrústegui, Pedro de la Villa
PURPOSE: To characterize the vision phenotype of mice lacking Aralar/AGC1/Slc25a12, the mitochondrial aspartate-glutamate carrier mutated in global cerebral hypomyelination (OMIM 612949). METHODS: We tested overnight dark-adapted control and aralar-deficient mice for the standard full electroretinogram (ERG) response. The metabolic stress of dark-adaptation was reduced by 5 min illumination after which the ERG response was monitored in darkness. We used the electrical response to two identical saturating light flashes (paired-flash stimulation) to isolate the inner retina and photoreceptor responses...
2016: Molecular Vision
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