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https://www.readbyqxmd.com/read/29158584/ketamine-enhances-structural-plasticity-in-mouse-mesencephalic-and-human-ipsc-derived-dopaminergic-neurons-via-ampar-driven-bdnf-and-mtor-signaling
#1
L Cavalleri, E Merlo Pich, M J Millan, C Chiamulera, T Kunath, P F Spano, G Collo
Among neurobiological mechanisms underlying antidepressant properties of ketamine, structural remodeling of prefrontal and hippocampal neurons has been proposed as critical. The suggested mechanism involves downstream activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which trigger mammalian target of rapamycin (mTOR)-dependent structural plasticity via brain-derived neurotrophic factor (BDNF) and protein neo-synthesis. We evaluated whether ketamine elicits similar molecular events in dopaminergic (DA) neurons, known to be affected in mood disorders, using a novel, translational strategy that involved mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158578/ketamine-and-its-metabolite-2r-6r-hydroxynorketamine-induce-lasting-alterations-in-glutamatergic-synaptic-plasticity-in-the-mesolimbic-circuit
#2
N Yao, O Skiteva, X Zhang, P Svenningsson, K Chergui
Low doses of ketamine trigger rapid and lasting antidepressant effects after one injection in treatment-resistant patients with major depressive disorder. Modulation of AMPA receptors (AMPARs) in the hippocampus and prefrontal cortex is suggested to mediate the antidepressant action of ketamine and of one of its metabolites (2R,6R)-hydroxynorketamine ((2R,6R)-HNK). We have examined whether ketamine and (2R,6R)-HNK affect glutamatergic transmission and plasticity in the mesolimbic system, brain regions known to have key roles in reward-motivated behaviors, mood and hedonic drive...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158577/vgf-function-in-depression-and-antidepressant-efficacy
#3
C Jiang, W-J Lin, M Sadahiro, B Labonté, C Menard, M L Pfau, C A Tamminga, G Turecki, E J Nestler, S J Russo, S R Salton
Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29155768/slice-patch-clamp-technique-for-analyzing-learning-induced-plasticity
#4
Hiroyuki Kida, Yuya Sakimoto, Dai Mitsushima
The slice patch clamp technique is a powerful tool for investigating learning-induced neural plasticity in specific brain regions. To analyze motor-learning induced plasticity, we trained rats using an accelerated rotor rod task. Rats performed the task 10 times at 30-s intervals for 1 or 2 days. Performance was significantly improved on the training days compared to the first trial. We then prepared acute brain slices of the primary motor cortex (M1) in untrained and trained rats. Current-clamp analysis showed dynamic changes in resting membrane potential, spike threshold, afterhyperpolarization, and membrane resistance in layer II/III pyramidal neurons...
November 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29154925/membrane-cholesterol-depletion-in-cortical-neurons-highlights-altered-nmda-receptor-functionality-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#5
Alessia Antonini, Silvia Caioli, Luana Saba, Giulia Vindigni, Silvia Biocca, Nadia Canu, Cristina Zona
Amyotrophic Lateral Sclerosis (ALS) is a chronic neurodegenerative disease affecting upper and lower motor neurons, with unknown aetiology. Lipid rafts, cholesterol enriched microdomains of the plasma membrane, have been linked to neurodegenerative disorders like ALS. The NMDA-receptor subcellular localization in lipid rafts is known to play many roles, from modulating memory strength to neurotoxicity. In this study, performed on the widely used G93A mouse model of ALS, we have shown an equal content of total membrane cholesterol in Control and G93A cortical cultures...
November 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29154130/neuropilin-2-plexina3-receptors-associate-with-glua1-and-mediate-sema3f-dependent-homeostatic-scaling-in-cortical-neurons
#6
Qiang Wang, Shu-Ling Chiu, Eleftheria Koropouli, Ingie Hong, Sarah Mitchell, Teresa P Easwaran, Natalie R Hamilton, Ahleah S Gustina, Qianwen Zhu, David D Ginty, Richard L Huganir, Alex L Kolodkin
Regulation of AMPA-type glutamate receptor (AMPAR) number at synapses is a major mechanism for controlling synaptic strength during homeostatic scaling in response to global changes in neural activity. We show that the secreted guidance cue semaphorin 3F (Sema3F) and its neuropilin-2 (Npn-2)/plexinA3 (PlexA3) holoreceptor mediate homeostatic plasticity in cortical neurons. Sema3F-Npn-2/PlexA3 signaling is essential for cell surface AMPAR homeostatic downscaling in response to an increase in neuronal activity, Npn-2 associates with AMPARs, and Sema3F regulates this interaction...
November 14, 2017: Neuron
https://www.readbyqxmd.com/read/29144968/a-synaptic-basis-for-glp-1-action-in-the-brain
#7
Sandrine Lefort, Matthias H Tschöp, Cristina García-Cáceres
Unraveling the brain control of metabolism may generate opportunities to discover novel precision medicines for obesity and diabetes. In this issue of Neuron, Liu et al. (2017) identify a novel glucagon-like peptide (GLP)-1 receptor-dependent signaling process that exerts anorexigenic action via the regulation of AMPA receptor subunit composition in the hypothalamus.
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29143219/glutamatergic-gabaergic-and-endocannabinoid-neurotransmissions-within-the-dorsal-hippocampus-modulate-the-cardiac-baroreflex-function-in-rats
#8
Nilson Carlos Ferreira-Junior, Davi Campos Lagatta, Leonardo Barbosa Moraes Resstel
The dorsal hippocampus (DH) is involved in the modulation of the cardiac baroreflex function. There is a wide expression of the NMDA and AMPA/Kainate receptors within the DH. Glutamate administration into the DH triggers both tachycardia and pressor responses. Moreover, GABAergic interneurons and endocannabinoid system play an important role in modulation of the activity of glutamatergic neurons within the DH. Therefore, the present work aimed to evaluate the involvement of the glutamatergic, GABAergic, and endocannabinoid neurotransmissions within the DH in cardiac baroreflex function in rats...
November 15, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29141213/cpeb2-activates-grasp1-mrna-translation-and-promotes-ampa-receptor-surface-expression-long-term-potentiation-and-memory
#9
Wen-Hsin Lu, Nai-Hsing Yeh, Yi-Shuian Huang
Activity-dependent synthesis of plasticity-related proteins is necessary to sustain long-lasting synaptic modifications and consolidate memory. We investigated the role of the translational regulator cytoplasmic polyadenylation element binding protein 2 (CPEB2) in learning and memory because regulated mRNA translation contributes to synaptic plasticity. Forebrain-restricted CPEB2 conditional knockout (cKO) mice exhibited impaired hippocampus-dependent memory in contextual fear conditioning and Morris water maze tests...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29138698/soluble-epoxide-hydrolase-inhibitor-and-14-15-epoxyeicosatrienoic-acid-facilitated-long-term-potentiation-through-camp-and-camkii-in-the-hippocampus
#10
Han-Fang Wu, Yi-Ju Chen, Su-Zhen Wu, Chi-Wei Lee, I-Tuan Chen, Yi-Chao Lee, Chi-Chen Huang, Chung-Hsi Hsing, Chih-Wei Tang, Hui-Ching Lin
Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation- (HFS-) induced long-term potentiation (LTP) and forskolin- (FSK-) induced LTP...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29137960/ampa-receptor-translocation-and-phosphorylation-are-induced-by-transcranial-direct-current-stimulation-in-rats
#11
Justin Stafford, Milene L Brownlow, Anthony Qualley, Ryan Jankord
Over the last decade, the interest in transcranial direct current stimulation (tDCS) has continued to increase, along with consideration of how it affects neuroplasticity mechanisms in the brain. Both human and animal studies have demonstrated numerous benefits and, although its application has increased, the neurophysiological mechanisms underlying tDCS' beneficial effects remain largely unknown. Recent studies have shown that long-term potentiation (LTP) increases following tDCS. In this work, we utilized a rodent model of tDCS to directly assess changes in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, a critical protein for enhancing synaptic transmission...
November 11, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29127904/pharmacokinetics-and-brain-uptake-study-of-novel-ampa-receptor-antagonist-perampanel-in-sd-rats-using-a-validated-uhplc-qtof-ms-method
#12
David Paul, Lingesh Allakonda, Amit Sahu, Shruti Surendran, Nanjappan Satheeshkumar
Perampanel (PER) is a novel AMPA receptor antagonist for antiepileptic therapy and is prospective for the treatment of other neurological disorders. A highly sensitive and rapid UHPLC-QTOF-MS method was developed for the quantification of PER in plasma/brain homogenate of SD rat with alogliptin as an internal standard (IS). Chromatographic separation was carried out on an Acquity UPLC HSS Cyano column (100mm×2.1mm, 1.8μm) using gradient mobile phase consisting of 0.1% formic acid and acetonitrile at a flow rate of 0...
November 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29123470/regulation-of-ampa-receptor-trafficking-by-protein-ubiquitination
#13
REVIEW
Jocelyn Widagdo, Sumasri Guntupalli, Se E Jang, Victor Anggono
The molecular mechanisms underlying plastic changes in the strength and connectivity of excitatory synapses have been studied extensively for the past few decades and remain the most attractive cellular models of learning and memory. One of the major mechanisms that regulate synaptic plasticity is the dynamic adjustment of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor content on the neuronal plasma membrane. The expression of surface AMPA receptors (AMPARs) is controlled by the delicate balance between the biosynthesis, dendritic transport, exocytosis, endocytosis, recycling and degradation of the receptors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29120510/in-vitro-characterization-of-gamma-oscillations-in-the-hippocampal-formation-of-the-domestic-chick
#14
Pradeep Dheerendra, Nicholas M Lynch, Joseph Crutwell, Mark O Cunningham, Tom V Smulders
Avian and mammalian brains have evolved independently from each other for about 300 million years. During that time, the hippocampal formation (HF) has diverged in morphology and cyto-architecture, but seems to have conserved much of its function. It is therefore an open question how seemingly different neural organizations can generate the same function. A prominent feature of the mammalian hippocampus is that it generates different neural oscillations, including the gamma rhythm, which plays an important role in memory processing...
November 9, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29118000/ca-2-calmodulin-binding-to-psd-95-mediates-homeostatic-synaptic-scaling-down
#15
Dhrubajyoti Chowdhury, Matthew Turner, Tommaso Patriarchi, Anne C Hergarden, David Anderson, Yonghong Zhang, Junqing Sun, Chao-Yin Chen, James B Ames, Johannes W Hell
Postsynaptic density protein-95 (PSD-95) localizes AMPA-type glutamate receptors (AMPARs) to postsynaptic sites of glutamatergic synapses. Its postsynaptic displacement is necessary for loss of AMPARs during homeostatic scaling down of synapses. Here, we demonstrate that upon Ca(2+) influx, Ca(2+)/calmodulin (Ca(2+)/CaM) binding to the N-terminus of PSD-95 mediates postsynaptic loss of PSD-95 and AMPARs during homeostatic scaling down. Our NMR structural analysis identified E17 within the PSD-95 N-terminus as important for binding to Ca(2+)/CaM by interacting with R126 on CaM...
November 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29116041/correction-super-resolution-imaging-of-synaptic-and-extra-synaptic-ampa-receptors-with-different-sized-fluorescent-probes
#16
Sang Hak Lee, Chaoyi Jin, En Cai, Pinghua Ge, Yuji Ishitsuka, Kai Wen Teng, Andre A de Thomaz, Duncan Nall, Murat Baday, Okunola Jeyifous, Daniel Demonte, Christopher M Dundas, Sheldon Park, Jary Y Delgado, William N Green, Paul R Selvin
No abstract text is available yet for this article.
November 8, 2017: ELife
https://www.readbyqxmd.com/read/29112849/astrocytes-supply-presynaptic-terminals-with-a-sweet-incentive-to-make-connections
#17
Giuseppe Condomitti, Joris de Wit
Glial cells shape neural circuits by secreting cues that contribute to the spatiotemporal control of connectivity. A new study in Neuron from Farhy-Tselnicker et al. (2017) shows that the astrocyte-secreted heparan sulfate proteoglycan GPC4 acts on presynaptic terminals to indirectly regulate AMPA receptor clustering and active synapse formation.
November 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29112674/interleukin-10-and-pd150606-modulate-expression-of-ampa-receptor-glua1-and-glua2-subunits-under-hypoxic-conditions
#18
Sergei G Levin, Nikolai P Sirota, Miroslav N Nenov, Tatyana A Savina, Oleg V Godukhin
The goal of this study was to evaluate the effects of anti-inflammatory cytokine, interleukin-10 (IL-10), and calpain inhibitor, PD150606, on the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits in rat hippocampal slices exposed to repeated brief hypoxic episodes. We studied both individual and combinatory effects of PD150606 and IL-10 on the expression of AMPA receptor subunits under hypoxic conditions for GluA1 and GluA2 as well as their phosphorylated forms - pSer831-GluA1 and pSer880-GluA2...
November 6, 2017: Neuroreport
https://www.readbyqxmd.com/read/29107806/chronic-hyperammonemia-alters-in-opposite-ways-membrane-expression-of-glua1-and-glua2-ampa-receptor-subunits-in-cerebellum-molecular-mechanisms-involved
#19
Andrea Cabrera-Pastor, Lucas Taoro-González, Esperanza López-Merino, Ferran Celma, Marta Llansola, Vicente Felipo
Hyperammonemia contributes to altered neurotransmission and cognition in patients with hepatic encephalopathy. Hyperammonemia in rats affects differently high- and low-affinity AMPA receptors (AMPARs) in cerebellum. We hypothesized that hyperammonemia would alter differently membrane expression of AMPARs GluA1 and GluA2 subunits by altering its phosphorylation. This work aims were: 1) assess if hyperammonemia alters GluA1 and GluA2 subunits membrane expression in cerebellum and 2) analyze the underlying mechanisms...
October 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29107522/-silent-nmda-synapses-enhance-motion-sensitivity-in-a-mature-retinal-circuit
#20
Santhosh Sethuramanujam, Xiaoyang Yao, Geoff deRosenroll, Kevin L Briggman, Greg D Field, Gautam B Awatramani
Retinal direction-selective ganglion cells (DSGCs) have the remarkable ability to encode motion over a wide range of contrasts, relying on well-coordinated excitation and inhibition (E/I). E/I is orchestrated by a diverse set of glutamatergic bipolar cells that drive DSGCs directly, as well as indirectly through feedforward GABAergic/cholinergic signals mediated by starburst amacrine cells. Determining how direction-selective responses are generated across varied stimulus conditions requires understanding how glutamate, acetylcholine, and GABA signals are precisely coordinated...
October 25, 2017: Neuron
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