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https://www.readbyqxmd.com/read/28642492/segregation-of-glutamatergic-and-cholinergic-transmission-at-the-mixed-motoneuron-renshaw-cell-synapse
#1
Boris Lamotte d'Incamps, Gardave S Bhumbra, Joshua D Foster, Marco Beato, Philippe Ascher
In neonatal mice motoneurons excite Renshaw cells by releasing both acetylcholine (ACh) and glutamate. These two neurotransmitters activate two types of nicotinic receptors (nAChRs) (the homomeric α7 receptors and the heteromeric α*ß* receptors) as well as the two types of glutamate receptors (GluRs) (AMPARs and NMDARs). Using paired recordings, we confirm that a single motoneuron can release both transmitters on a single post-synaptic Renshaw cell. We then show that co-transmission is preserved in adult animals...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630296/subunit-specific-role-for-the-amino-terminal-domain-of-ampa-receptors-in-synaptic-targeting
#2
Javier Díaz-Alonso, Yujiao J Sun, Adam J Granger, Jonathan M Levy, Sabine M Blankenship, Roger A Nicoll
The amino-terminal domain (ATD) of AMPA receptors (AMPARs) accounts for approximately 50% of the protein, yet its functional role, if any, remains a mystery. We have discovered that the translocation of surface GluA1, but not GluA2, AMPAR subunits to the synapse requires the ATD. GluA1A2 heteromers in which the ATD of GluA1 is absent fail to translocate, establishing a critical role of the ATD of GluA1. Inserting GFP into the ATD interferes with the constitutive synaptic trafficking of GluA1, but not GluA2, mimicking the deletion of the ATD...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28621662/chronic-lithium-treatment-elicits-its-antimanic-effects-via-bdnf-trkb-dependent-synaptic-downscaling
#3
Erinn S Gideons, Pei-Yi Lin, Melissa Mahgoub, Ege T Kavalali, Lisa M Monteggia
Lithium is widely used as a treatment for Bipolar Disorder although the molecular mechanisms that underlie its therapeutic effects are under debate. In this study, we show brain-derived neurotrophic factor (BDNF) is required for the antimanic-like effects of lithium but not the antidepressant-like effects in mice. We performed whole cell patch clamp recordings of hippocampal neurons to determine the impact of lithium on synaptic transmission that may underlie the behavioral effects. Lithium produced a significant decrease in α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated miniature excitatory postsynaptic current (mEPSC) amplitudes due to postsynaptic homeostatic plasticity that was dependent on BDNF and its receptor tropomyosin receptor kinase B (TrkB)...
June 16, 2017: ELife
https://www.readbyqxmd.com/read/28621434/eea1-restores-homeostatic-synaptic-plasticity-in-hippocampal-neurons-from-rett-syndrome-mice
#4
Xin Xu, Lucas Pozzo-Miller
Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in MECP2, the gene encoding the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2). Deletion of Mecp2 in mice results in an imbalance of synaptic excitation and inhibition in hippocampal pyramidal neurons, which affects "Hebbian" long-term synaptic plasticity. Since the excitatory/inhibitory (E/I) balance is maintained by homeostatic mechanisms, we examined the role of MeCP2 in homeostatic synaptic plasticity (HSP) at excitatory synapses...
June 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28608780/signalling-through-ampa-receptors-on-oligodendrocyte-precursors-promotes-myelination-by-enhancing-oligodendrocyte-survival
#5
Eleni Kougioumtzidou, Takahiro Shimizu, Nicola B Hamilton, Koujiro Tohyama, Rolf Sprengel, Hannah Monyer, David Attwell, William D Richardson
Myelin, made by oligodendrocytes, is essential for rapid information transfer in the central nervous system. Oligodendrocyte precursors (OPs) receive glutamatergic synaptic input from axons but how this affects their development is unclear. Murine OPs in white matter express AMPA receptor (AMPAR) subunits GluA2, GluA3 and GluA4. We generated mice in which OPs lack both GluA2 and GluA3, or all three subunits GluA2/3/4, which respectively reduced or abolished AMPAR-mediated input to OPs. In both double- and triple-knockouts OP proliferation and number were unchanged but ~25% fewer oligodendrocytes survived in the subcortical white matter during development...
June 13, 2017: ELife
https://www.readbyqxmd.com/read/28607044/regulation-of-spinogenesis-in-mature-purkinje-cells-via-mglur-pkc-mediated-phosphorylation-of-camkii%C3%AE
#6
Takeyuki Sugawara, Chihiro Hisatsune, Hiroyuki Miyamoto, Naoko Ogawa, Katsuhiko Mikoshiba
Dendritic spines of Purkinje cells form excitatory synapses with parallel fiber terminals, which are the primary sites for cerebellar synaptic plasticity. Nevertheless, how density and morphology of these spines are properly maintained in mature Purkinje cells is not well understood. Here we show an activity-dependent mechanism that represses excessive spine development in mature Purkinje cells. We found that CaMKIIβ promotes spine formation and elongation in Purkinje cells through its F-actin bundling activity...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28604739/autism-like-behaviours-and-enhanced-memory-formation-and-synaptic-plasticity-in-lrfn2-salm1-deficient-mice
#7
Naoko Morimura, Hiroki Yasuda, Kazuhiko Yamaguchi, Kei-Ichi Katayama, Minoru Hatayama, Naoko H Tomioka, Maya Odagawa, Akiko Kamiya, Yoshimi Iwayama, Motoko Maekawa, Kazuhiko Nakamura, Hideo Matsuzaki, Masatsugu Tsujii, Kazuyuki Yamada, Takeo Yoshikawa, Jun Aruga
Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. However its role in higher brain function and underlying mechanisms remain unknown. Here, we show that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory. In the hippocampus, the levels of synaptic PSD-95 and GluA1 are decreased...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28603025/the-ampa-receptor-positive-allosteric-modulator-s-47445-rescues-in%C3%A2-vivo-ca3-ca1-long-term-potentiation-and-structural-synaptic-changes-in-old-mice
#8
Albert Giralt, María Ángeles Gómez-Climent, Rafael Alcalá, Sylvie Bretin, Daniel Bertrand, José María Delgado-García, Esther Pérez-Navarro, Jordi Alberch, Agnès Gruart
Positive allosteric modulators of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are small molecules that decrease deactivation of AMPARs via an allosteric site. These molecules keep the receptor in an active state. Interestingly, this type of modulator has been proposed for treating cognitive decline in ageing, dementias, and Alzheimer's disease (AD). S 47445 (8-cyclopropyl-3-[2-(3-fluorophenyl)ethyl]-7,8-dihydro-3H-[1,3]oxazino[6,5-g][1,2,3]benzotriazine-4,9-dione) is a novel AMPAR positive allosteric modulator (AMPA-PAM)...
June 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28585865/protein-kinase-c-epsilon-delays-latency-until-anoxic-depolarization-through-arc-expression-and-glur2-internalization
#9
Charles H Cohan, Holly M Stradecki-Cohan, Kahlilia C Morris-Blanco, Nathalie Khoury, Kevin B Koronowski, Mehdi Youbi, Clinton B Wright, Miguel A Perez-Pinzon
Global cerebral ischemia is a debilitating injury that damages the CA1 region of the hippocampus, an area important for learning and memory. Protein kinase C epsilon (PKCɛ) activation is a critical component of many neuroprotective treatments. The ability of PKCɛ activation to regulate AMPA receptors (AMPARs) remains unexplored despite the role of AMPARs in excitotoxicity after brain ischemia. We determined that PKCɛ activation increased expression of a protein linked to learning and memory, activity-regulated cytoskeleton-associated protein (arc)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28582391/all-atom-nmda-receptor-transmembrane-domain-model-development-and-simulations-in-lipid-bilayers-and-water
#10
Samaneh Mesbahi-Vasey, Lea Veras, Michael Yonkunas, Jon W Johnson, Maria G Kurnikova
N-methyl-d-aspartate receptors (NMDARs) are members of the ionotropic glutamate receptor family that mediate excitatory synaptic transmission in the central nervous system. The channels of NMDARs are permeable to Ca2+ but blocked by Mg2+, distinctive properties that underlie essential brain processes such as induction of synaptic plasticity. However, due to limited structural information about the NMDAR transmembrane ion channel forming domain, the mechanism of divalent cation permeation and block is understood poorly...
2017: PloS One
https://www.readbyqxmd.com/read/28578480/acute-neuroinflammation-promotes-cell-responses-to-1800%C3%A2-mhz-gsm-electromagnetic-fields-in-the-rat-cerebral-cortex
#11
Julie Lameth, Annie Gervais, Catherine Colin, Philippe Lévêque, Thérèse M Jay, Jean-Marc Edeline, Michel Mallat
Mobile phone communications are conveyed by radiofrequency (RF) electromagnetic fields, including pulse-modulated global system for mobile communications (GSM)-1800 MHz, whose effects on the CNS affected by pathological states remain to be specified. Here, we investigated whether a 2-h head-only exposure to GSM-1800 MHz could impact on a neuroinflammatory reaction triggered by lipopolysaccharide (LPS) in 2-week-old or adult rats. We focused on the cerebral cortex in which the specific absorption rate (SAR) of RF averaged 2...
June 3, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28575718/sleep-homeostasis-habits-and-habituation
#12
REVIEW
Vladyslav V Vyazovskiy, Mark E Walton, Stuart N Peirson, David M Bannerman
The importance of sleep for behavioural performance during waking is long-established, but the underlying reasons and mechanisms remain elusive. Waking and sleep are associated with changes in the levels of GluA1 AMPAR subunit in synaptic membranes, while studies using genetically-modified mice have identified an important role for GluA1-dependent synaptic plasticity in a non-associative form of memory that underlies short-term habituation to recently experienced stimuli. Here we posit that sleep may play a role in dishabituation, which restores attentional capacity and maximises the readiness of the animal for learning and goal-directed behaviour during subsequent wakefulness...
May 30, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28571973/development-of-novel-n-3-bromoisoxazolin-5-yl-substituted-2-3-benzodiazepines-as-noncompetitive-ampar-antagonists
#13
Milad Espahbodinia, Roberta Ettari, Wei Wen, Andrew Wu, Yu-Chuan Shen, Li Niu, Silvana Grasso, Maria Zappalà
In this work, we designed and synthesized novel N-3-bromoisoxazolin-5-yl substituted 2,3-benzodiazepines as noncompetitive AMPAR antagonists, with the aim that this heterocycle could establish favourable interactions with a putative binding pocket of the receptor, like the thiadiazole nucleus of GYKI 47409 does. Within this investigation, we identified some active molecules and, among these 2,3-benzodiazepines, 4c showed a much improved inhibitory potency as compared with unsubstituted 2,3-benzodiazepines.
May 19, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28559374/tarp-%C3%AE-2-is-required-for-inflammation-associated-ampa-receptor-plasticity-within-lamina-ii-of-the-spinal-cord-dorsal-horn
#14
Steve J Sullivan, Mark Farrant, Stuart G Cull-Candy
In the brain, transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs) critically influence the distribution, gating, and pharmacology of AMPARs, but the contribution of these auxiliary subunits to AMPAR-mediated signaling in the spinal cord remains unclear. We found that the type I TARP γ-2 (stargazin) is present in lamina II of the superficial dorsal horn (SDH), an area involved in nociception. Consistent with the notion that γ-2 is associated with surface AMPARs, CNQX, a partial agonist at AMPARs associated with type I TARPs, evoked whole-cell currents in lamina II neurons, but such currents were severely attenuated in γ-2-lacking stargazer (stg/stg) mice...
May 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28554859/microtubule-associated-protein-tau-contributes-to-intra-dendritic-trafficking-of-ampa-receptors-in-multiple
#15
Mamiko Suzuki, Tetsuya Kimura
Microtubule-associated protein tau has crucial roles not only in the formation of some neurodegenerative disorders but also in normal synaptic functions, although its contributions to these are still unclear. Here, to reveal the influence of tau deletion on trafficking of synaptic receptors, we investigated the distribution of GluA2-containing AMPA-type glutamate receptors (AMPARs) within neuronal dendrites in wild-type and tau-deficient neurons using biochemical and laser-confocal imaging techniques. Under basal conditions, expression of GluA2 at tau-deficient synapses was almost normal; however, its level within dendrites in tau-deficient neurons was greater than that in wild-type neurons...
May 26, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28550530/rtms-ameliorates-ptsd-symptoms-in-rats-by-enhancing-glutamate-transmission-and-synaptic-plasticity-in-the-acc-via-the-pten-akt-signalling-pathway
#16
Gaohua Liu, Dayun Feng, Jian Wang, Haifeng Zhang, Zhengwu Peng, Min Cai, Jing Yang, Ruiguo Zhang, Huaning Wang, Shengxi Wu, Qingrong Tan
Repetitive transcranial magnetic stimulation (rTMS) is a novel physiological therapy that has been adopted to clinically treat psychiatric disorders. Our previous study indicated the potential therapeutic effect of rTMS on posttraumatic stress disorder (PTSD). However, the exact molecular mechanism is elusive. Currently, using the single prolonged stress (SPS) rat model for PTSD, we investigated the glutamatergic transmission and neural plasticity changes in the anterior cingulate cortex (ACC) after SPS induction and explored the protective effects and mechanism of rTMS treatment...
May 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28549968/autophagy-regulated-ampar-subunit-upregulation-in-in-vitro-oxygen-glucose-deprivation-reoxygenation-induced-hippocampal-injury
#17
Li Bao, Rong-Hu Li, Mei Li, Mei-Fang Jin, Gang Li, Xing Han, Yuan-Yuan Yang, Bin Sun, Li-Xiao Xu, Xing Feng
Autophagy has been implicated to mediate experimental cerebral ischemia/ reperfusion-induced neuronal death; the underlying molecular mechanisms, though, are poorly understood. In this study, we investigated the role of autophagy in regulating the expression of AMPAR subunits (GluR1, GluR2, and GluR3) in oxygen glucose deprivation/reperfusion (OGD/R)-mediated injury of hippocampal neurons. Our results showed that, OGD/R-induced hippocampal neuron injury was accompanied by accumulation of autophagosomes and autolysosomes in cytoplasm alongside a dramatic increase in expression of autophagy-related genes, LC3 and Beclin 1 and increased intracellular Ca(2+) levels...
May 23, 2017: Brain Research
https://www.readbyqxmd.com/read/28543279/role-of-ampa-receptors-in-homocysteine-nmdar-induced-crosstalk-between-erk-and-p38-map-kinase
#18
Ranjana Poddar, Alexandria Chen, Lucas Winter, Sathyanarayanan Rajagopal, Surojit Paul
Homocysteine, a metabolite of the methionine cycle has been reported to play a role in neurotoxicity through activation of NMDAR-mediated signaling pathway. The proposed mechanisms associated with homocysteine-NMDAR induced neurotoxicity involve a unique signaling pathway that triggers a crosstalk between ERK and p38 MAPKs, where activation of p38 MAPK is downstream of and dependent on ERK MAPK. However, the molecular basis of the ERK MAPK mediated p38 MAPK activation is not understood. The current study investigates whether AMPARs play a role in facilitating the ERK MAPK mediated p38 MAPK activation...
May 24, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28541473/relationship-between-synaptic-ampar-and-spine-dynamics-impairments-in-the-fxs-mouse
#19
Anand Suresh, Anna Dunaevsky
Structural dynamics of dendritic spines are important for memory and learning and are impaired in neurodevelopmental disorders such as fragile X syndrome. Spine dynamics are regulated by activity-dependent mechanisms that involve modulation of AMPA receptors (AMPAR); however, the relationship between AMPAR and spine dynamics in vivo and how these are altered in FXS mouse model is not known. Here, we tracked AMPAR and spines over multiple days in vivo in the cortex and found that dendritic spines in the fmr1 KO mouse were denser, smaller, had higher turnover rates and contained less sGluA2 compared to littermate controls...
May 24, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28539424/ca-2-permeable-ampars-mediate-glutamatergic-transmission-and-excitotoxic-damage-at-the-hair-cell-ribbon-synapse
#20
Joy Y Sebe, Soyoun Cho, Lavinia Sheets, Mark A Rutherford, Henrique von Gersdorff, David W Raible
We report functional and structural evidence for GluA2-lacking Ca(2+)-permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By utilizing the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of in vivo electrophysiological and Ca(2+) imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca(2+) influx into afferent terminals...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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