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https://www.readbyqxmd.com/read/28077487/calcium-permeable-ampa-receptors-and-silent%C3%A2-synapses-in-cocaine-conditioned-place-preference
#1
Avani Shukla, Anna Beroun, Myrto Panopoulou, Peter A Neumann, Seth Gn Grant, M Foster Olive, Yan Dong, Oliver M Schlüter
Exposure to cocaine generates silent synapses in the nucleus accumbens (NAc), whose eventual unsilencing/maturation by recruitment of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) after drug withdrawal results in profound remodeling of NAc neuro-circuits. Silent synapse-based NAc remodeling was shown to be critical for several drug-induced behaviors, but its role in acquisition and retention of the association between drug rewarding effects and drug-associated contexts has remained unclear. Here, we find that the postsynaptic proteins PSD-93, PSD-95, and SAP102 differentially regulate excitatory synapse properties in the NAc...
January 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28077092/phylogenetic-analysis-of-ionotropic-l-glutamate-receptor-genes-in-the-bilateria-with-special-notes-on-aplysia-californica
#2
Justin B Greer, Sawsan Khuri, Lynne A Fieber
BACKGROUND: The neurotransmitter L-Glutamate (L-Glu) acting at ionotropic L-Glu receptors (iGluR) conveys fast excitatory signal transmission in the nervous systems of all animals. iGluR-dependent neurotransmission is a key component of the synaptic plasticity that underlies learning and memory. During learning, two subtypes of iGluR, α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) and N-methyl-D-aspartate receptors (NMDAR), are dynamically regulated postsynaptically in vertebrates...
January 11, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28069928/functional-organization-of-cutaneous-and-muscle-afferent-synapses-onto-immature-spinal-lamina-i-projection-neurons
#3
Jie Li, Mark L Baccei
: It is well-established that sensory afferents innervating muscle are more effective at inducing hyperexcitability within spinal cord circuits compared to skin afferents, which likely contributes to the higher prevalence of chronic musculoskeletal pain compared to pain of cutaneous origin. However, the mechanisms underlying these differences in central nociceptive signaling remain incompletely understood, as nothing is known about how superficial dorsal horn (SDH) neurons process sensory input from muscle vs...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28063882/mice-lacking-grip1-2-show-increased-social-interactions-and-enhanced-phosphorylation-at-glua2-s880
#4
Mei Han, Rebeca Mejias, Shu-Ling Chiu, Rebecca Rose, Abby Adamczyk, Richard Huganir, Tao Wang
Glutamate receptor interacting proteins 1 and 2 (GRIP1/2) play an important role in regulating synaptic trafficking of AMPA receptor 2/3 (GluA2/3) and synaptic strength. Gain-of-function GRIP1 mutations are implicated in social behavioral deficits in autism. To study mechanisms of Grip1/2-mediated AMPA signaling in the regulation of social behaviors, we performed social behavioral testing on neuron-specific Grip1/2-double knockout (DKO) and wild type (WT) mice that are matched for age, sex, and strain background...
January 4, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28063880/glur3b-ab-s-induced-oligodendrocyte-precursor-cells-excitotoxicity-via-mitochondrial-dysfunction
#5
Yi Liu, Yan Chen, Wan Tong Du, Xiu Xiang Wu, Fu Xing Dong, Xue Bin Qu, Hong Bin Fan, Rui Qin Yao
Studies have indicated that glutamate receptor subunit 3 peptide B antibodies (GluR3B Ab's) by directing against a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype glutamate receptors (AMPARs) subunit 3 (GluR3B) was involved in the hippocampal neuron damage in the pathogenesis of epilepsy. Glutamate accumulation is critical for oligodendrocyte precursors (OPCs) excitotoxic injury. However, remarkably little is known about whether GluR3B Ab's causes OPCs excitotoxicity, and the underlying mechanisms remain unclear...
January 4, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28057533/presynaptic-pick1-facilitates-trafficking-of-ampa-receptors-between-active-zone-and-synaptic-vesicle-pool
#6
C Haglerød, S Hussain, Y Nakamura, J Xia, F M Haug, O P Ottersen, J M Henley, S Davanger
Previous studies have indicated that presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) contribute to the regulation of neurotransmitter release. In hippocampal synapses, the presynaptic surface expression of several AMPAR subunits, including GluA2, is regulated in a ligand-dependent manner. However, the molecular mechanisms underlying the presynaptic trafficking of AMPARs are still unknown. Here, using bright-field immunocytochemistry, western blots, and quantitative immunogold electron microscopy of the hippocampal CA1 area from intact adult rat brain, we demonstrate the association of AMPA receptors with the presynaptic active zone and with small presynaptic vesicles, in Schaffer collateral synapses in CA1 of the hippocampus...
January 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28045462/hippocampal-encoding-of-interoceptive-context-during-fear-conditioning
#7
S-W Yoo, M Bae, L B Tovar-Y-Romo, N J Haughey
Rodent models of auditory fear conditioning are often used to understand the molecular mechanisms regulating fear- and anxiety-related behaviors. Conditioning and extinction memories are influenced by contextual cues, and the reinstatement of conditioned fear occurs when the conditioning stimulus is presented in a context different from the extinction context. Although it has been proposed that internal state is a feature of context that could influence extinction, contributions of interoception to conditioning have not been experimentally addressed...
January 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28033671/visual-experience-dependent-regulation-of-neuronal-structure-and-function-by-histone-deacetylase-1-in-developing-xenopus-tectum-in-vivo
#8
Hangze Ruan, Juanmei Gao, Xianjie Qi, Yi Tao, Xia Guo, Zhaoyi Guo, Lijun Zheng, Yaling Song, Yuan Liao, Wanhua Shen
Histone deacetylase 1 (HDAC1) is thought to play pivotal roles in neurogenesis and neurodegeneration. However, the role of HDAC1 in neuronal growth and structural plasticity in the developing brain in vivo remains unclear. Here, we show that in the optic tectum of Xenopus laevis, HDAC1 knockdown dramatically decreased the frequency of AMPAR-mediated synaptic currents and increased the frequency of GABAAR-mediated currents, whereas HDAC1 overexpression significantly decreased the frequency of GABAAR-mediated synaptic currents...
December 29, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/28025067/dopamine-d1-like-receptor-in-lateral-habenula-nucleus-affects-contextual-fear-memory-and-long-term-potentiation-in-hippocampal-ca1-in-rats
#9
Jiangping Chan, Xin Guan, Yiling Ni, Lilu Luo, Liqiang Yang, Pengyue Zhang, Jichuan Zhang, Yanmei Chen
The Lateral Habenula (LHb) plays an important role in emotion and cognition. Recent experiments suggest that LHb has functional interaction with the hippocampus and plays an important role in spatial learning. LHb is reciprocally connected with midbrain monoaminergic brain areas such as the ventral tegmental area (VTA). However, the role of dopamine type 1 receptor (D1R) in LHb in learning and memory is not clear yet. In the present study, D1R agonist or antagonist were administered bilaterally into the LHb in rats...
December 23, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/28011638/a-critical-role-for-ubiquitination-in-the-endocytosis-of-glutamate-receptors
#10
Ravinder Gulia, Rohan Sharma, Samarjit Bhattacharyya
Group I metabotropic glutamate receptors (mGluRs) play important roles in various neuronal processes and they elicit changes in synaptic efficacy through AMPAR endocytosis. Trafficking of mGluRs plays important roles in controlling the precise localization of these receptors at specific region of the cell as well as it regulates the activity of these receptors. Despite this obvious significance we know very little about the cellular mechanisms that control the trafficking of group I mGluRs. We show here that ligand-mediated internalization of group I mGluRs is ubiquitination dependent...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28009436/pharmacological-characterisation-of-n-2s-5-6-fluoro-3-pyridinyl-2-3-dihydro-1h-inden-2-yl-2-propanesulfonamide-a-novel-clinical-ampa-receptor-positive-allosteric-modulator
#11
Simon E Ward, Paul Beswick, Novella Calcinaghi, Lee A Dawson, Jane Gartlon, Francesca Graziani, Declan N C Jones, Laurent Lacroix, M H Selina Mok, Beatrice Oliosi, Joanne Pardoe, Kathryn Starr, Marie L Woolley, Mark H Harries
BACKGROUND AND PURPOSE: AMPA receptor positive allosteric modulators represent a potential therapeutic strategy to improve cognition in people with schizophrenia. These studies collectively constitute the pre-clinical pharmacology data package used to build confidence in the pharmacology of this molecule and enable a clinical trial application. EXPERIMENTAL APPROACH: [N-[(2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro 1H-inden-2-yl]-2-propanesulfonamide] (UoS12258) was profiled in a number of in vitro and in vivo studies to highlight its suitability as a novel therapeutic agent...
December 23, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28002633/vta-da-neuron-excitatory-synapses-in-shank3-%C3%AE-ex-4-9-mouse-line
#12
Bariselli Sebastiano, Bellone Camilla
SHANK3 proteins belong to the Shank/ProSAP family, which contain five-conserved domains - the ankyrin (ANK) repeated, the Src homology 3 (SH3), the PSD-95/Discs large/ZO-1 (PDZ), the proline-rich and the sterile alpha motif (SAM; Sheng and Kim, 2000). SHANK proteins are located at the postsynaptic density of excitatory synapses and indirectly link the metabotropic (mGluRs) and the ionotropic glutamate receptor (iGluRs: AMPARs, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and NMDARs, N-methyl-D-aspartate receptors) via different domains (Naisbitt et al...
December 21, 2016: Synapse
https://www.readbyqxmd.com/read/27997885/streptozotocin-inhibits-electrophysiological-determinants-of-excitatory-and-inhibitory-synaptic-transmission-in-ca1-pyramidal-neurons-of-rat-hippocampal-slices-reduction-of-these-effects-by-edaravone
#13
Ting Ju, Yuru Li, Xiaoran Wang, Lifeng Xiao, Li Jiang, Shanshan Zhou, Meimei Yang, Tingting Zhao, Lina Sun, Tingjiao Liu, Jinghan Lin, Yi Xu, Liming Zhang
BACKGROUND: Streptozotocin (STZ) has served as an agent to generate an Alzheimer's disease (AD) model in rats, while edaravone (EDA), a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27993521/trafficking-of-calcium-permeable-and-calcium-impermeable-ampa-receptors-in-nucleus-accumbens-medium-spiny-neurons-co-cultured-with-prefrontal-cortex-neurons
#14
Craig T Werner, Conor H Murray, Jeremy M Reimers, Niravkumar M Chauhan, Kenneth K Y Woo, Hanna M Molla, Jessica A Loweth, Marina E Wolf
AMPA receptor (AMPAR) transmission onto medium spiny neurons (MSNs) of the adult rat nucleus accumbens (NAc) is normally dominated by GluA2-containing, Ca(2+)-impermeable AMPAR (CI-AMPARs). However, GluA2-lacking, Ca(2+)-permeable AMPA receptors (CP-AMPARs) accumulate after prolonged withdrawal from extended-access cocaine self-administration and thereafter their activation is required for the intensified (incubated) cue-induced cocaine craving that characterizes prolonged withdrawal from such regimens. These findings suggest the existence of mechanisms in NAc MSNs that differentially regulate CI-AMPARs and CP-AMPARs...
December 16, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27993520/overexpression-of-%C3%AE-camkii-impairs-behavioral-flexibility-and-nmdar-dependent-long-term-depression-in-the-dentate-gyrus
#15
Pengcheng Yin, Hao Xu, Qi Wang, Jiayue Wang, Liang Yin, Meichen Xu, Zhenyang Xie, Wenzhao Liu, Xiaohua Cao
Behavioral flexibility is in close proximity to dentate gyrus (DG) function and long-term depression (LTD), but the role of DG LTD in behavioral flexibility has hitherto been unexplored. Although the functions of alpha-Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) have been studied extensively, the role of βCaMKII, a constituent of the CaMKII holoenzyme, in LTD and behavioral flexibility has not been investigated in vivo. Here using the βCaMKII-F90G transgenic (TG) mice, in which the inducible and reversible overexpression of βCaMKII is restricted to dentate gyrus (DG), we found that TG mice exhibited defective behavioral flexibility in two reversal tasks and seriously impaired N-methyl-d-aspartic acid receptor (NMDAR)-dependent LTD in DG medial perforant path (MPP)...
December 16, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27993509/reggie-1-and-reggie-2-flotillins-participate-in-rab11a-dependent-cargo-trafficking-spine-synapse-formation-and-ltp-related-ampa-receptor-glua1-surface-exposure-in-mouse-hippocampal-neurons
#16
Vsevolod Bodrikov, Aline Pauschert, Gaga Kochlamazashvili, Claudia A O Stuermer
Reggie-1 and -2 (flotillins) reside at recycling vesicles and promote jointly with Rab11a the targeted delivery of cargo. Recycling is essential for synapse formation suggesting that reggies and Rab11a may regulate the development of spine synapses. Recycling vesicles provide cargo for dendritic growth and recycle surface glutamate receptors (AMPAR, GluA) for long-term potentiation (LTP) induced surface exposure. Here, we show reduced number of spine synapses and impairment of an in vitro correlate of LTP in hippocampal neurons from reggie-1 k...
December 16, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27976681/amphetamine-and-methamphetamine-increase-nmdar-glun2b-synaptic-currents-in-midbrain-dopamine-neurons
#17
Minghua Li, Suzanne M Underhill, Cheryl Reed, Tamara J Phillips, Susan G Amara, Susan L Ingram
The psychostimulants amphetamine (AMPH) and methamphetamine (MA) are widely abused illicit drugs. Here we show that both psychostimulants acutely increase NMDA receptor (NMDAR)-mediated synaptic currents and decrease AMPAR/NMDAR ratios in midbrain dopamine neurons. The potentiation depends on the transport of AMPH into the cell by the dopamine transporter (DAT). NMDAR-GluN2B receptor inhibitors, ifenprodil, RO 25-6981 and RO 04-5595 inhibit the potentiation without affecting basal evoked NMDA currents, indicating that NMDAR-GluN2B receptors are activated by AMPH...
December 15, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27960077/eif2%C3%AE-mediated-translational-control-regulates-the-persistence-of-cocaine-induced-ltp-in-midbrain-dopamine-neurons
#18
Andon N Placzek, Gonzalo Viana Di Prisco, Sanjeev Khatiwada, Martina Sgritta, Wei Huang, Krešimir Krnjević, Randal J Kaufman, John A Dani, Peter Walter, Mauro Costa-Mattioli
Recreational drug use leads to compulsive substance abuse in some individuals. Studies on animal models of drug addiction indicate that persistent long-term potentiation (LTP) of excitatory synaptic transmission onto ventral tegmental area (VTA) dopamine (DA) neurons is a critical component of sustained drug seeking. However, little is known about the mechanism regulating such long-lasting changes in synaptic strength. Previously, we identified that translational control by eIF2α phosphorylation (p-eIF2α) regulates cocaine-induced LTP in the VTA (Huang et al...
December 13, 2016: ELife
https://www.readbyqxmd.com/read/27956638/palmitoylation-regulates-glutamate-receptor-distributions-in-postsynaptic-densities-through-control-of-psd95-conformation-and-orientation
#19
Okunola Jeyifous, Eric I Lin, Xiaobing Chen, Sarah E Antinone, Ryan Mastro, Renaldo Drisdel, Thomas S Reese, William N Green
Postsynaptic density protein 95 (PSD95) and synapse-associated protein 97 (SAP97) are homologous scaffold proteins with different N-terminal domains, possessing either a palmitoylation site (PSD95) or an L27 domain (SAP97). Here, we measured PSD95 and SAP97 conformation in vitro and in postsynaptic densities (PSDs) using FRET and EM, and examined how conformation regulated interactions with AMPA-type and NMDA-type glutamate receptors (AMPARs/NMDARs). Palmitoylation of PSD95 changed its conformation from a compact to an extended configuration...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27955702/%C3%AE-amyloid-triggers-aberrant-over-scaling-of-homeostatic-synaptic-plasticity
#20
James Gilbert, Shu Shu, Xin Yang, Youming Lu, Ling-Qiang Zhu, Heng-Ye Man
The over-production of β-amyloid (Aβ) has been strongly correlated to neuronal dysfunction and altered synaptic plasticity in Alzheimer's disease (AD). Accordingly, it has been proposed that disrupted synaptic transmission and neuronal network instability underlie memory failure that is evident in the early phases of AD. Homeostatic synaptic plasticity (HSP) serves to restrain neuronal activity within a physiological range. Therefore a disruption of this mechanism may lead to destabilization in synaptic and neural circuit function...
December 13, 2016: Acta Neuropathologica Communications
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