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https://www.readbyqxmd.com/read/29467630/neural-cellular-and-molecular-mechanisms-of-active-forgetting
#1
REVIEW
Jorge H Medina
The neurobiology of memory formation attracts much attention in the last five decades. Conversely, the rules that govern and the mechanisms underlying forgetting are less understood. In addition to retroactive interference, retrieval-induced forgetting and passive decay of time, it has been recently demonstrated that the nervous system has a diversity of active and inherent processes involved in forgetting. In Drosophila , some operate mainly at an early stage of memory formation and involves dopamine (DA) neurons, specific postsynaptic DA receptor subtypes, Rac1 activation and induces rapid active forgetting...
2018: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/29467308/comparing-the-antiseizure-and-neuroprotective-efficacy-of-ly293558-diazepam-caramiphen-and-ly293558-caramiphen-combination-against-soman-in-a-rat-model-relevant-to-the-pediatric-population
#2
James P Apland, Vassiliki Aroniadou-Anderjaska, Taiza H Figueiredo, Volodymyr I Pidoplichko, Katia Rossetti, Maria F M Braga
The currently FDA-approved anticonvulsant for the treatment of status epilepticus (SE) induced by nerve agents is the benzodiazepine diazepam. However, diazepam does not appear to offer neuroprotective benefits. This is particularly concerning with respect to the protection of children, because in the developing brain, synaptic transmission mediated via GABAA receptors, the target of diazepam, is still weak. In the present study, we exposed 21-day-old male rats to 1.2xLD50 soman, and compared the antiseizure, anti-lethality, and neuroprotective efficacy of diazepam (10 mg/kg), LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (an antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and LY293558 (15 mg/kg)+caramiphen (50 mg/kg), administered 1 h post-exposure...
February 21, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29464195/danger-changes-the-way-the-mammalian-brain-stores-information-about-innocuous-events-a-study-of-sensory-preconditioning-in-rats
#3
Nathan M Holmes, Mukesh Raipuria, Omar A Qureshi, Simon Killcross, Fred Westbrook
The amygdala is a critical substrate for learning about cues that signal danger. Less is known about its role in processing innocuous or background information. The present study addressed this question using a sensory preconditioning protocol in male rats. In each experiment, rats were exposed to pairings of two innocuous stimuli in stage 1, S2 and S1, and then to pairings of S1 and shock in stage 2. As a consequence of this training, control rats displayed defensive reactions (freezing) when tested with both S2 and S1...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29460436/truncating-variants-of-the-dlg4-gene-are-responsible-for-intellectual-disability-with-marfanoid-features
#4
M Sébastien, B Ange-Line, A Mirna, C Martin, S Elisabeth, G Cyril, G Anne-Marie, C Aude, C Perrine, H Delphine, F Anne, H Nada, V Antonio, T-M-T Frédéric, P Christophe, D Yannis, T-R Christel, F Laurence
Marfanoid habitus (MH) combined with intellectual disability (ID) is a genetically and clinically heterogeneous group of overlapping disorders. We performed exome sequencing in 33 trios and 31 single probands to identify novel genes specific to MH-ID. After the search for variants in OMIM genes and non-OMIM genes with classical approaches, we searched for variants in non-disease-causing genes whose pLI was above 0.9 (ExAC Consortium data), in which truncating variants were found in at least 3 unrelated patients, in order to identity novel MH-ID genes...
February 20, 2018: Clinical Genetics
https://www.readbyqxmd.com/read/29452226/quantitative-proteomic-analysis-reveals-synaptic-dysfunction-in-the-amygdala-of-rats-susceptible-to-chronic-mild-stress
#5
Mi Zhou, Zhao Liu, Jia Yu, Shuiming Li, Min Tang, Li Zeng, Haiyang Wang, Hong Xie, Li Peng, Haojun Huang, Chanjuan Zhou, Peng Xie, Jian Zhou
The amygdala plays a key role in the pathophysiology of depression, but the molecular mechanisms underlying amygdalar hyperactivity in depression remain unclear. In this study, we used a chronic mild stress (CMS) protocol to separate susceptible and insusceptible rat subgroups. Proteomes in the amygdalae were analyzed differentially across subgroups based on labeling with isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry. Of 2,562 quantified proteins, 102 were differentially expressed...
February 13, 2018: Neuroscience
https://www.readbyqxmd.com/read/29451794/-s-2-amino-3-5-methyl-3-hydroxyisoxazol-4-yl-propanoic-acid-ampa-and-kainate-receptor-ligands-further-exploration-of-bioisosteric-replacements-structural-and-biological-investigation
#6
Simone Brogi, Margherita Brindisi, Stefania Butini, Giridhar Uttam Kshirsagar, Samuele Maramai, Giulia Chemi, Sandra Gemma, Giuseppe Campiani, Ettore Novellino, Paolo Fiorenzani, Jessica Pinassi, Anna Maria Aloisi, Mikko Gynther, Raminta Venskutonyte, Liwei Han, Karla Frydenvang, Jette Sandholm Kastrup, Darryl S Pickering
Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1 and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip).
February 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29449802/sparc-and-glua1-containing-ampa-receptors-promote-neuronal-health-following-cns-injury
#7
Emma V Jones, Yann Bernardinelli, Juan G Zarruk, Sabrina Chierzi, Keith K Murai
The proper formation and maintenance of functional synapses in the central nervous system (CNS) requires communication between neurons and astrocytes and the ability of astrocytes to release neuromodulatory molecules. Previously, we described a novel role for the astrocyte-secreted matricellular protein SPARC (Secreted Protein, Acidic and Rich in Cysteine) in regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and plasticity at developing synapses. SPARC is highly expressed by astrocytes and microglia during CNS development but its level is reduced in adulthood...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29448101/neuronal-calcium-channel-%C3%AE-1-subunit-interacts-with-ampa-receptor-increasing-its-cell-surface-localisation
#8
Bo Am Seo, Jung-Ha Lee, Ho Min Kim, Myoung-Goo Kang
Voltage-activated Ca 2+ channels (Ca v ) play critical roles in excitable cells including neurons. Unlike the well-defined roles of Ca v 2 for pre-synaptic neurotransmission, the post-synaptic function of Ca v 2 is unclear. Based on our previous study demonstrating the postsynaptic association of the Ca v 2 with the AMPA receptor (AMPA-R), in this study we sought to further analyse the Ca v 2-AMPA-R association. We used a step-by-step dissociation of partially purified native Ca v 2-AMPA-R complexes and co-immunoprecipitation of the Ca v 2-AMPA-R complexes expressed in HEK293T cells to demonstrate that the main subunit of Ca v , α 1 , formed a complex with the AMPA-R without the auxiliary subunits β, α 2 δ, γ 2/3 ...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29444074/self-crowding-of-ampa-receptors-in-the-excitatory-postsynaptic-density-can-effectuate-anomalous-receptor-sub-diffusion
#9
Rahul Gupta
AMPA receptors (AMPARs) and their associations with auxiliary transmembrane proteins are bulky structures with large steric-exclusion volumes. Hence, self-crowding of AMPARs, depending on the local density, may affect their lateral diffusion in the postsynaptic membrane as well as in the highly crowded postsynaptic density (PSD) at excitatory synapses. Earlier theoretical studies considered only the roles of transmembrane obstacles and the AMPAR-binding submembranous scaffold proteins in shaping receptor diffusion within PSD...
February 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29442555/direct-intertectal-inputs-are-an-integral-component-of-the-bilateral-sensorimotor-circuit-for-behavior-in-xenopus-tadpoles
#10
Abigail C Gambrill, Regina L Faulkner, Hollis T Cline
The circuit controlling visually-guided behavior in non-mammalian vertebrates, like Xenopus tadpoles, includes retinal projections to the contralateral optic tectum, where visual information is processed, and tectal motor outputs projecting ipsilaterally to hindbrain and spinal cord. Tadpoles have an intertectal commissure whose function is unknown, but it might transfer information between the tectal lobes. Differences in visual experience between the two eyes have profound effects on the development and function of visual circuits in animals with binocular vision, but the effects on animals with fully-crossed retinal projections are not clear...
February 14, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29437380/ligand-directed-chemistry-of-ampa-receptors-confers-live-cell-fluorescent-biosensors
#11
Shigeki Kiyonaka, Seiji Sakamoto, Sho Wakayama, Yuma Morikawa, Muneo Tsujikawa, Itaru Hamachi
AMPA-type glutamate receptors (AMPARs) mediate fast excitatory synaptic transmission in the central nervous system. Disregulation of AMPAR function is associated with many kinds of neurological, neurodegenerative and psychiatric disorders. As a result, molecules capable of controlling AMPAR functions are potential therapeutic agents. Fluorescent semisynthetic biosensors have attracted considerable interest for the discovery of ligands selectively acting on target proteins. Given the large protein complex formation of AMPARs in live cells, biosensors using full-length AMPARs retaining original functionality are ideal for drug screening...
February 13, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29434817/%C3%AE-opioid-receptor-inhibition-prevents-remifentanil-induced-post-operative-hyperalgesia-via-regulating-glur1-trafficking-and-ampa-receptor-function
#12
Aifen Liu, Xiaopeng Wang, Hui Wang, Guoyi Lv, Yize Li, Hongmei Li
The interaction of remifentanil with glutamate systems has an important role in remifentanil-induced thermal and mechanical hyperalgesia. A previous study by our group suggested that the trafficking and function of glutamate receptor 1 (GluR1) subunits contributes to remifentanil-induced hyperalgesia by regulating the phosphorylation of GluR1 in dorsal horn neurons. The present study demonstrated that δ opioid receptor (DOR) inhibition prevented thermal and mechanical hyperalgesia, which was induced by remifentanil infusion via attenuating GluR1 subunit trafficking and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) function in dorsal horn neurons...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29432883/regulation-of-phosphorylation-of-ampa-glutamate-receptors-by-muscarinic-m4-receptors-in-the-striatum-in-vivo
#13
Li-Min Mao, Nan He, Dao-Zhong Jin, John Q Wang
The acetylcholine muscarinic 4 (M4) receptor is a principal muscarinic receptor subtype present in the striatum. Notably, Gαi/o-coupled M4 receptors and Gαs/Golf-coupled dopamine D1 receptors are coexpressed in striatonigral projection neurons and are thought to interact with each other to regulate neuronal excitability, although underlying molecular mechanisms are poorly understood. In this study, we investigated the role of M4 receptors in the regulation of phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the rat normal and dopamine-stimulated striatum in vivo...
February 9, 2018: Neuroscience
https://www.readbyqxmd.com/read/29432698/long-term-depression-induced-by-endogenous-cannabinoids-produces-neuroprotection-via-astroglial-cb1r-after-stroke-in-rodents
#14
Feng Wang, Jing Han, Haruki Higashimori, Jingyi Wang, Jingjing Liu, Li Tong, Yongjie Yang, Hailong Dong, Xia Zhang, Lize Xiong
Ischemia not only activates cell death pathways but also triggers endogenous protective mechanisms. However, it is largely unknown what is the essence of the endogenous neuroprotective mechanisms induced by preconditioning. In this study we demonstrated that systemic injection of JZL195, a selective inhibitor of eCB clearance enzymes, induces in vivo long-term depression at CA3-CA1 synapses and at PrL-NAc synapses produces neuroprotection. JZL195-elicited long-term depression is blocked by AM281, the antagonist of cannabinoid 1 receptor (CB1R) and is abolished in mice lacking cannabinoid CB1 receptor (CB1R) in astroglial cells, but is conserved in mice lacking CB1R in glutamatergic or GABAergic neurons...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29430619/a-regulatory-circuitry-between-gria2-mir-409-and-mir-495-is-affected-by-als-fus-mutation-in-esc-derived-motor-neurons
#15
Davide Capauto, Alessio Colantoni, Lei Lu, Tiziana Santini, Giovanna Peruzzi, Silvia Biscarini, Mariangela Morlando, Neil A Shneider, Elisa Caffarelli, Pietro Laneve, Irene Bozzoni
Mutations in fused in sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS). FUS is a multifunctional protein involved in the biogenesis and activity of several types of RNAs, and its role in the pathogenesis of ALS may involve both direct effects of disease-associated mutations through gain- and loss-of-function mechanisms and indirect effects due to the cross talk between different classes of FUS-dependent RNAs. To explore how FUS mutations impinge on motor neuron-specific RNA-based circuitries, we performed transcriptome profiling of small and long RNAs of motor neurons (MNs) derived from mouse embryonic stem cells carrying a FUS-P517L knock-in mutation, which is equivalent to human FUS-P525L, associated with a severe and juvenile-onset form of ALS...
February 12, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29426177/large-variation-in-glyphosate-mineralization-in-21-different-agricultural-soils-explained-by-soil-properties
#16
Nghia Khoi Nguyen, Ulrike Dörfler, Gerhard Welzl, Jean Charles Munch, Reiner Schroll, Marjetka Suhadolc
Glyphosate and its main metabolite aminomethylphosphonic acid (AMPA) have frequently been detected in surface water and groundwaters. Since adequate glyphosate mineralization in soil may reduce its losses to environment, improved understanding of site specific factors underlying pesticide mineralization in soils is needed. The aim of this study was to investigate the relationship between soil properties and glyphosate mineralization. To establish a sound basis for resilient correlations, the study was conducted with a large number of 21 agricultural soils, differing in a variety of soil parameters, such as soil texture, soil organic matter content, pH, exchangeable ions etc...
January 30, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29425490/fast-spiking-interneurons-supply-feedforward-control-of-bursting-calcium-and-plasticity-for-efficient-learning
#17
Scott F Owen, Joshua D Berke, Anatol C Kreitzer
Fast-spiking interneurons (FSIs) are a prominent class of forebrain GABAergic cells implicated in two seemingly independent network functions: gain control and network plasticity. Little is known, however, about how these roles interact. Here, we use a combination of cell-type-specific ablation, optogenetics, electrophysiology, imaging, and behavior to describe a unified mechanism by which striatal FSIs control burst firing, calcium influx, and synaptic plasticity in neighboring medium spiny projection neurons (MSNs)...
February 8, 2018: Cell
https://www.readbyqxmd.com/read/29422839/exercise-induced-fatigue-impairs-bidirectional-corticostriatal-synaptic-plasticity
#18
Jing Ma, Huimin Chen, Xiaoli Liu, Lingtao Zhang, Decai Qiao
Exercise-induced fatigue (EF) is a ubiquitous phenomenon in sports competition and training. It can impair athletes' motor skill execution and cognition. Corticostriatal synaptic plasticity is considered to be the cellular mechanism of movement control and motor learning. However, the effect of EF on corticostriatal synaptic plasticity remains elusive. In the present study, using field excitatory postsynaptic potential recording, we found that the corticostriatal long-term potentiation (LTP) and long-term depression (LTD) were both impaired in EF mice...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29422059/hyperammonemia-alters-membrane-expression-of-glua1-and-glua2-subunits-of-ampa-receptors-in-hippocampus-by-enhancing-activation-of-the-il-1-receptor-underlying-mechanisms
#19
Lucas Taoro-Gonzalez, Yaiza M Arenas, Andrea Cabrera-Pastor, Vicente Felipo
BACKGROUND: Hyperammonemic rats reproduce the cognitive alterations of patients with hepatic encephalopathy, including altered spatial memory, attributed to altered membrane expression of AMPA receptor subunits in hippocampus. Neuroinflammation mediates these cognitive alterations. We hypothesized that hyperammonemia-induced increase in IL-1β in hippocampus would be responsible for the altered GluA1 and GluA2 membrane expression. The aims of this work were to (1) assess if increased IL-1β levels and activation of its receptor are responsible for the changes in GluA1 and/or GluA2 membrane expression in hyperammonemia and (2) identify the mechanisms by which activation of IL-1 receptor leads to altered membrane expression of GluA1 and GluA2...
February 8, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29419376/orphan-receptor-gpr158-controls-stress-induced-depression
#20
Laurie P Sutton, Cesare Orlandi, Chenghui Song, Won Chan Oh, Brian S Muntean, Keqiang Xie, Alice Filippini, Xiangyang Xie, Rachel Satterfield, Jazmine D W Yaeger, Kenneth J Renner, Samuel M Young, Baoji Xu, Hyungbae Kwon, Kirill A Martemyanov
Stress can be a motivational force for decisive action and adapting to novel environment; whereas, exposure to chronic stress contributes to the development of depression and anxiety. However, the molecular mechanisms underlying stress-responsive behaviors are not fully understood. Here, we identified the orphan receptor GPR158 as a novel regulator operating in the prefrontal cortex (PFC) that links chronic stress to depression. GPR158 is highly upregulated in the PFC of human subjects with major depressive disorder...
February 8, 2018: ELife
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