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https://www.readbyqxmd.com/read/28921719/inflammation-alters-ampa-stimulated-calcium-responses-in-dorsal-striatal-d2-but-not-d1-spiny-projection-neurons
#1
Carissa D Winland, Nora Welsh, Alberto Sepulveda-Rodriguez, Stefano Vicini, Kathleen A Maguire-Zeiss
Neuroinflammation precedes neuronal loss in striatal neurodegenerative diseases and can be exacerbated by the release of proinflammatory molecules by microglia. These molecules can affect trafficking of AMPARs. The preferential trafficking of calcium-permeable versus impermeable AMPARs can result in disruptions of [Ca(2+) ]i and alter cellular functions. In striatal neurodegenerative diseases, changes in [Ca(2+) ]i and L-type voltage-gated calcium channels (VGCCs) have been reported. Therefore, the present study sought to determine whether a proinflammatory environment alters AMPA-stimulated [Ca(2+) ]i through calcium-permeable AMPARs and/or L-type VGCCs in dopamine-2 and dopamine-1 expressing striatal spiny projection neurons (D2 and D1 SPNs) in the dorsal striatum...
September 16, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28919534/glutamate-induced-rapid-induction-of-arc-arg3-1-requires-nmda-receptor-mediated-phosphorylation-of-erk-and-creb
#2
Tao Chen, Jie Zhu, Li-Kun Yang, Yi Feng, Wei Lin, Yu-Hai Wang
Arc/Arg3.1 is a unique immediate early gene whose expression is highly dynamic and correlated with various forms of synaptic plasticity. Many previous reports highlight the complexity of mechanisms that regulate Arc/Arg3.1 expression in neurons. In the present study, the expression and regulation of Arc/Arg3.1 after glutamate treatment in primary cultured cortical neurons were investigated. We found that both Arc/Arg3.1 mRNA and Arc/Arg3.1 protein dynamically increased within 24h after glutamate treatment. The results of immunostaining showed that abundant amounts of Arc/Arg3...
September 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28919175/slow-ampar-synaptic-transmission-is-determined-by-stargazin-and-glutamate-transporters
#3
Hsin-Wei Lu, Timothy S Balmer, Gabriel E Romero, Laurence O Trussell
AMPARs mediate the briefest synaptic currents in the brain by virtue of their rapid gating kinetics. However, at the mossy fiber-to-unipolar brush cell synapse in the cerebellum, AMPAR-mediated EPSCs last for hundreds of milliseconds, and it has been proposed that this time course reflects slow diffusion from a complex synaptic space. We show that upon release of glutamate, synaptic AMPARs were desensitized by transmitter by >90%. As glutamate levels subsequently fell, recovery of transmission occurred due to the presence of the AMPAR accessory protein stargazin that enhances the AMPAR response to low levels of transmitter...
September 8, 2017: Neuron
https://www.readbyqxmd.com/read/28912687/alterations-in-properties-of-glutamatergic-transmission-in-the-temporal-cortex-and-hippocampus-following-pilocarpine-induced-acute-seizures-in-wistar-rats
#4
Dmitry V Amakhin, Sergey L Malkin, Julia L Ergina, Kirill A Kryukov, Ekaterina A Veniaminova, Olga E Zubareva, Aleksey V Zaitsev
Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in humans, and is often developed after an initial precipitating brain injury. This form of epilepsy is frequently resistant to pharmacological treatment; therefore, the prevention of TLE is the prospective approach to TLE therapy. The lithium-pilocarpine model in rats replicates some of the main features of TLE in human, including the pathogenic mechanisms of cell damage and epileptogenesis after a primary brain injury. In the present study, we investigated changes in the properties of glutamatergic transmission during the first 3 days after pilocarpine-induced acute seizures in Wistar rats (PILO-rats)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28904854/protein-kinase-c-regulates-ampa-receptor-auxiliary-protein-shisa9-ckamp44-through-interactions-with-neuronal-scaffold-pick1
#5
Stella-Amrei Kunde, Nils Rademacher, Hanna Zieger, Sarah A Shoichet
Synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors are essential mediators of neurotransmission in the central nervous system. Shisa9/cysteine-knot AMPAR modulating protein 44 (CKAMP44) is a transmembrane protein recently found to be present in AMPA receptor-associated protein complexes. Here, we show that the cytosolic tail of Shisa9/CKAMP44 interacts with multiple scaffold proteins that are important for regulating synaptic plasticity in central neurons. We focussed on the interaction with the scaffold protein PICK1, which facilitates the formation of a tripartite complex with the protein kinase C (PKC) and thereby regulates phosphorylation of Shisa9/CKAMP44 C-terminal residues...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28904092/map1b-light-chain-modulates-synaptic-transmission-via-ampa-receptor-intracellular-trapping
#6
Rocío Palenzuela, Yolanda Gutiérrez, Jonathan E Draffin, Argentina Lario, Marion Benoist, José A Esteban
The regulated transport of AMPA-type glutamate receptors (AMPARs) to the synaptic membrane is a key mechanism to determine the strength of excitatory synaptic transmission in the brain. In this work, we uncovered a new role for the microtubule-associated protein MAP1B, in modulating the access of AMPARs to the postsynaptic membrane. Using mice and rats of either sex, we show that MAP1B light chain (LC) accumulates in the somatodendritic compartment of hippocampal neurons, where it forms immobile complexes on microtubules that limit vesicular transport...
September 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28902836/hippocampal-ltp-and-contextual-learning-require-surface-diffusion-of-ampa-receptors
#7
A C Penn, C L Zhang, F Georges, L Royer, C Breillat, E Hosy, J D Petersen, Y Humeau, D Choquet
Long-term potentiation (LTP) of excitatory synaptic transmission has long been considered a cellular correlate for learning and memory. Early LTP (less than 1 h) had initially been explained either by presynaptic increases in glutamate release or by direct modification of postsynaptic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor function. Compelling models have more recently proposed that synaptic potentiation can occur by the recruitment of additional postsynaptic AMPA receptors (AMPARs), sourced either from an intracellular reserve pool by exocytosis or from nearby extra-synaptic receptors pre-existing on the neuronal surface...
September 13, 2017: Nature
https://www.readbyqxmd.com/read/28901289/distinct-stages-of-synapse-elimination-are-induced-by-burst-firing-of-ca1-neurons-and-differentially-require-mef2a-d
#8
Chia-Wei Chang, Julia Wilkerson, Carly Hale, Jay R Gibson, Kimberly M Huber
Experience and activity refine cortical circuits through synapse elimination, but little is known about the activity patterns and downstream molecular mechanisms that mediate this process. We used optogenetics to drive individual mouse CA1 hippocampal neurons to fire in theta frequency bursts to understand how cell autonomous, postsynaptic activity leads to synapse elimination. Brief (1hr) periods of postsynaptic bursting selectively depressed AMPA receptor (R) synaptic transmission, or silenced excitatory synapses, whereas more prolonged (24 hr) firing depressed both AMPAR and NMDAR EPSCs and eliminated spines, indicative of a synapse elimination...
September 13, 2017: ELife
https://www.readbyqxmd.com/read/28894415/loss-of-fmrp-impaired-hippocampal-long-term-plasticity-and-spatial-learning-in-rats
#9
Yonglu Tian, Chaojuan Yang, Shujiang Shang, Yijun Cai, Xiaofei Deng, Jian Zhang, Feng Shao, Desheng Zhu, Yunbo Liu, Guiquan Chen, Jing Liang, Qiang Sun, Zilong Qiu, Chen Zhang
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP). In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate Fmr1 knockout (KO) rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1(exon4-KO) )...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28890421/the-mechanistic-link-between-arc-arg3-1-expression-and-ampa-receptor-endocytosis
#10
REVIEW
Mark J Wall, Sonia A L Corrêa
The activity-regulated cytoskeleton associated protein (Arc/Arg3.1) plays a key role in determining synaptic strength through facilitation of AMPA receptor (AMPAR) endocytosis. Although there is considerable data on the mechanism by which Arc induction controls synaptic plasticity and learning behaviours, several key mechanistic questions remain. Here we review data on the link between Arc expression and the clathrin-mediated endocytic pathway which internalises AMPARs and discuss the significance of Arc binding to the clathrin adaptor protein 2 (AP-2) and to endophilin/dynamin...
September 7, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28890075/down-regulation-of-dorsal-striatal-%C3%AE-camkii-causes-striatum-related-cognitive-and-synaptic-disorders
#11
Qi Wang, Pengcheng Yin, Bin Yu, Zheng Zhao, Gal Richter-Levin, Lu Yu, Xiaohua Cao
Alpha calcium/calmodulin dependent protein kinase II (αCaMKII) is a serine/threonine protein kinase which is expressed abundantly in dorsal striatum and is highly involved in the corticostriatal synaptic plasticity. Nevertheless, it currently remains unclear whether and how αCaMKII plays a in the striatum-related neural disorders. To address the above issue, lentivirus-mediated short hairpin RNA (shRNA) was used to silence the expression of αCaMKII gene in the dorsal striatum of mice. As a consequence of down-regulation of dorsal striatal αCaMKII expression, we observed defective motor skill learning in accelerating rotarod and response learning in water cross maze...
September 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28888867/pick1facilitates-lasting-reduction-in-glua2-concentration-in-the-hippocampus-during-chronic-epilepsy
#12
Jan-Øyvind Lorgen, Daniel Lawer Egbenya, Janniche Hammer, Svend Davanger
Overstimulation of glutamate receptors resulting in excessive intracellular calcium concentrations is a major cause of neuronal cell death in epilepsy. The main source of increased calcium concentration during this excitotoxicity is an influx through NMDA subtype of glutamate receptors. The GluR2 hypothesis states that following a neurological insult such as an epileptic seizure, the AMPAR subunit GluR2 protein is down regulated. This increases the likelihood of the formation of GluR2-lacking, calcium-permeable AMPARs which might further enhance the toxicity of the neurotransmitter, glutamate...
August 31, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28878629/higher-arc-nucleus-to-cytoplasm-ratio-during-sleep-in-the-superficial-layers-of-the-mouse-cortex
#13
Sakiko Honjoh, Luisa de Vivo, Hiroyuki Okuno, Haruhiko Bito, Giulio Tononi, Chiara Cirelli
The activity-regulated cytoskeleton associated protein Arc is strongly and quickly upregulated by neuronal activity, synaptic potentiation and learning. Arc entry in the synapse is followed by the endocytosis of glutamatergic AMPA receptors (AMPARs), and its nuclear accumulation has been shown in vitro to result in a small decline in the transcription of the GluA1 subunit of AMPARs. Since these effects result in a decline in synaptic strength, we asked whether a change in Arc dynamics may temporally correlate with sleep-dependent GluA1 down-regulation...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/28878050/antibody-associated-cns-syndromes-without-signs-of-inflammation-in-the-elderly
#14
Domingo Escudero, Mar Guasp, Helena Ariño, Carles Gaig, Eugenia Martínez-Hernández, Josep Dalmau, Francesc Graus
OBJECTIVE: To report the CNS syndromes of patients ≥60 years of age with antibodies against neuronal surface antigens but no evidence of brain MRI and CSF inflammatory changes. METHODS: This was a retrospective clinical analysis of patients with antibodies against neuronal surface antigens who fulfilled 3 criteria: age ≥60 years, no inflammatory abnormalities in brain MRI, and no CSF pleocytosis. Antibodies were determined with reported techniques. RESULTS: Among 155 patients ≥60 years of age with neurologic syndromes related to antibodies against neuronal surface antigens, 35 (22...
September 6, 2017: Neurology
https://www.readbyqxmd.com/read/28865912/inhibition-of-ampa-receptor-and-camkii-activity-in-the-lateral-habenula-reduces-depressive-like-behavior-and-alcohol-intake-in-rats
#15
Jing Li, Seungwoo Kang, Rao Fu, Liangzhi Wu, Wei Wu, Hongwei Liu, Danielle Gregor, Wanhong Zuo, Alex Bekker, Jiang-Hong Ye
Depression is a well-known risk factor for developing relapse drinking, but the neuronal mechanisms underlying the interactions between depression and alcohol use disorders remain elusive. Accumulating evidence has associated depression with hyperactivity of the lateral habenula (LHb), an epithalamic structure in the brain that encodes aversive signals. Glutamate receptors contribute substantially to the excitability of LHb neurons. Glutamatergic synapses in LHb neurons largely express GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) that can be modulated by Ca(2+)/calmodulin-dependent protein II (CaMKII)...
August 31, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28865021/role-of-drebrin-in-synaptic-plasticity
#16
Yuko Sekino, Noriko Koganezawa, Toshiyuki Mizui, Tomoaki Shirao
Synaptic plasticity underlies higher brain function such as learning and memory, and the actin cytoskeleton in dendritic spines composing excitatory postsynaptic sites plays a pivotal role in synaptic plasticity. In this chapter, we review the role of drebrin in the regulation of the actin cytoskeleton during synaptic plasticity, under long-term potentiation (LTP) and long-term depression (LTD). Dendritic spines have two F-actin pools, drebrin-decorated stable F-actin (DF-actin) and drebrin-free dynamic F-actin (FF-actin)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28864821/timely-regulated-sorting-from-early-to-late-endosomes-is-required-to-maintain-cerebellar-long-term-depression
#17
Taegon Kim, Yukio Yamamoto, Keiko Tanaka-Yamamoto
An important feature of long-term synaptic plasticity is the prolonged maintenance of plastic changes in synaptic transmission. The trafficking of AMPA-type glutamate receptors (AMPARs) is involved in the expression of many forms of synaptic plasticity, yet the subsequent events accomplishing the maintenance of plastic changes in synaptic AMPAR numbers are not fully understood. Here, we find that maintenance of cerebellar long-term depression results from a reduction in the number of AMPARs residing within endocytic recycling pathways...
September 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28855251/pick1-regulates-ampa-receptor-endocytosis-via-direct-interactions-with-ap2-%C3%AE-appendage-and-dynamin
#18
Maria Fiuza, Christine M Rostosky, Gabrielle T Parkinson, Alexei M Bygrave, Nagaraj Halemani, Marcio Baptista, Ira Milosevic, Jonathan G Hanley
Clathrin-mediated endocytosis (CME) is used to internalize a diverse range of cargo proteins from the cell surface, often in response to specific signals. In neurons, the rapid endocytosis of GluA2-containing AMPA receptors (AMPARs) in response to NMDA receptor (NMDAR) stimulation causes a reduction in synaptic strength and is the central mechanism for long-term depression, which underlies certain forms of learning. The mechanisms that link NMDAR activation to CME of AMPARs remain elusive. PICK1 is a BAR domain protein required for NMDAR-dependent reductions in surface GluA2; however, the molecular mechanisms involved are unclear...
August 30, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28815591/engineering-defined-membrane-embedded-elements-of-ampa-receptor-induces-opposing-gating-modulation-by-cnih3-and-stargazin
#19
Natalie Hawken, Elena Zaika, Terunaga Nakagawa
During excitatory synaptic transmission, various structurally unrelated transmembrane auxiliary subunits control the function of AMPA receptors (AMPARs), but the underlying mechanisms remain unclear. We identified lipid-exposed residues in the transmembrane domain (TMD) of GluA2 subunit of AMPARs that are critical for the function of AMPAR auxiliary subunits, stargazin (Stg) and cornichon 3 (CNIH3). These residues are essential for stabilizing the AMPAR-CNIH3 complex in detergents and overlap with the contacts made between GluA2 TMD and Stg in the cryoEM structures...
August 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28793258/crucial-roles-for-sirt2-and-ampa-receptor-acetylation-in-synaptic-plasticity-and-memory
#20
Guan Wang, Shaomin Li, James Gilbert, Howard J Gritton, Zemin Wang, Zhangyuan Li, Xue Han, Dennis J Selkoe, Heng-Ye Man
AMPA receptors (AMPARs) mediate fast excitatory synaptic transmission and are crucial for synaptic plasticity, learning, and memory. However, the molecular control of AMPAR stability and its neurophysiological significance remain unclear. Here, we report that AMPARs are subject to lysine acetylation at their C termini. Acetylation reduces AMPAR internalization and degradation, leading to increased cell-surface localization and prolonged receptor half-life. Through competition for the same lysine residues, acetylation intensity is inversely related to the levels of AMPAR ubiquitination...
August 8, 2017: Cell Reports
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