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Excitatory glutamate receptors

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https://www.readbyqxmd.com/read/29350907/excitatory-and-inhibitory-neuronal-circuits-in-the-spinal-cord-and-their-role-in-the-control-of-motor-neuron-function-and-degeneration
#1
Uri Nimrod Ramírez-Jarquín, Ricardo Tapia
The complex neuronal networks of the spinal cord coordinate a wide variety of motor functions, including walking, running and voluntary and involuntary movements. This is accomplished by different groups of neurons, called center pattern generators, which control left-right alternation and flexor-extensor patterns. These spinal circuits, located in the ventral horns, are formed by several neuronal types, and the specific function of most of them has been identified by means of studies in vivo and in the isolated spinal cord of mice harboring genetically induced ablation of specific neuronal populations...
January 19, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29346767/functional-principles-of-posterior-septal-inputs-to-the-medial-habenula
#2
Yo Otsu, Salvatore Lecca, Katarzyna Pietrajtis, Charly Vincent Rousseau, Païkan Marcaggi, Guillaume Pierre Dugué, Caroline Mailhes-Hamon, Manuel Mameli, Marco Alberto Diana
The medial habenula (MHb) is an epithalamic hub contributing to expression and extinction of aversive states by bridging forebrain areas and midbrain monoaminergic centers. Although contradictory information exists regarding their synaptic properties, the physiology of the excitatory inputs to the MHb from the posterior septum remains elusive. Here, combining optogenetics-based mapping with ex vivo and in vivo physiology, we examine the synaptic properties of posterior septal afferents to the MHb and how they influence behavior...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346754/input-specific-nmdar-dependent-potentiation-of-dendritic-gabaergic-inhibition
#3
Chiayu Q Chiu, James S Martenson, Maya Yamazaki, Rie Natsume, Kenji Sakimura, Susumu Tomita, Steven J Tavalin, Michael J Higley
Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors leads to input-specific long-term potentiation of dendritic inhibition mediated by somatostatin-expressing interneurons...
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29339535/functional-changes-of-ampa-responses-in-human-induced-pluripotent-stem-cell-derived-neural-progenitors-in-fragile-x-syndrome
#4
Venkat Swaroop Achuta, Tommi Möykkynen, Ulla-Kaisa Peteri, Giorgio Turconi, Claudio Rivera, Kari Keinänen, Maija L Castrén
Altered neuronal network formation and function involving dysregulated excitatory and inhibitory circuits are associated with fragile X syndrome (FXS). We examined functional maturation of the excitatory transmission system in FXS by investigating the response of FXS patient-derived neural progenitor cells to the glutamate analog (AMPA). Neural progenitors derived from induced pluripotent stem cell (iPSC) lines generated from boys with FXS had augmented intracellular Ca2+ responses to AMPA and kainate that were mediated by Ca2+-permeable AMPA receptors (CP-AMPARs) lacking the GluA2 subunit...
January 16, 2018: Science Signaling
https://www.readbyqxmd.com/read/29339293/methylphenidate-significantly-alters-the-functional-coupling-between-the-prefrontal-cortex-and-dopamine-neurons-in-the-ventral-tegmental-area
#5
Ike C Dela Peña, Guofang Shen, Wei-Xing Shi
Amphetamine-like psychostimulants, including methylphenidate, have been shown to produce two opposing effects on dopamine (DA) neurons: a DA receptor-mediated feedback inhibition and a non-DA receptor-mediated excitation. To test whether the latter effect is mediated through the prefrontal cortex (PFC), we made dual-site recordings from the PFC and ventral tegmental area (VTA). Consistent with previous reports, methylphenidate inhibited VTA DA neurons. The D2 receptor antagonist raclopride completely reversed the inhibition and further increased the activity, particularly bursting, to above pre-drug baseline...
January 12, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29330065/stargazin-differentially-modulates-ampakine-gating-kinetics-and-pharmacology
#6
Daniel P Radin, Yong-Xin Li, Gary Rogers, Richard Purcell, Arnold Lippa
It was previously reported that Stargazin (STG) enhances the surface expression of AMPA receptors, controls receptor gating and slows channel desensitization as an auxiliary subunit of the receptors. Ampakines are a class of AMPA receptor positive allosteric modulators that modify rates of transmitter binding, channel activity and desensitization parameters. As such, they have shown efficacy in animal models of neurodegenerative diseases, where excitatory synaptic transmission is compromised. Given the functional similarities between STG and ampakines, the current study sought to probe interactions between STG and ampakine gating properties...
January 9, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29328021/the-presynaptic-ribbon-maintains-vesicle-populations-at-the-hair-cell-afferent-fiber-synapse
#7
Lars Becker, Michael E Schnee, Mamiko Niwa, Willy Sun, Stephan Maxeiner, Sara Talaei, Bechara Kachar, Mark A Rutherford, Anthony J Ricci
The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon's contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; high stimulus level rescued exocytosis in KO...
January 12, 2018: ELife
https://www.readbyqxmd.com/read/29315624/prenatal-alcohol-exposure-increases-histamine-h3-receptor-mediated-inhibition-of-glutamatergic-neurotransmission-in-rat-dentate-gyrus
#8
Rafael K Varaschin, Nyika A Allen, Martina J Rosenberg, C Fernando Valenzuela, Daniel D Savage
BACKGROUND: We have reported that prenatal alcohol exposure (PAE)-induced deficits in dentate gyrus, long-term potentiation (LTP), and memory are ameliorated by the histamine H3 receptor inverse agonist ABT-239. Curiously, ABT-239 did not enhance LTP or memory in control offspring. Here, we initiated an investigation of how PAE alters histaminergic neurotransmission in the dentate gyrus and other brain regions employing combined radiohistochemical and electrophysiological approaches in vitro to examine histamine H3 receptor number and function...
December 5, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29311144/differentiation-and-characterization-of-excitatory-and-inhibitory-synapses-by-cryo-electron-tomography-and-correlative-microscopy
#9
Chang-Lu Tao, Yun-Tao Liu, Rong Sun, Bin Zhang, Lei Qi, Sakar Shivakoti, Chong-Li Tian, Peijun Zhang, Pak-Ming Lau, Z Hong Zhou, Guo-Qiang Bi
As key functional units in neural circuits, different types of neuronal synapses play distinct roles in brain information processing, learning and memory. Synaptic abnormalities are believed to underlie various neurological and psychiatric disorders. Here, by combining cryo-electron tomography and cryo-correlative light and electron microscopy, we distinguished intact excitatory and inhibitory synapses of cultured hippocampal neurons, and visualized the in situ three-dimensional organization of synaptic organelles and macromolecules in their native state...
January 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29274351/high-fat-diet-induced-hyperglutamatergic-activation-of-the-hippocampus-in-mice-a-proton-magnetic-resonance-spectroscopy-study-at-9-4t
#10
Song-I Lim, Kyu-Ho Song, Chi-Hyeon Yoo, Dong-Cheol Woo, Bo-Young Choe
The aim of this study was to investigate the long-term neurochemical alterations in the hippocampus of mice fed a high-fat diet (HFD) while plasma leptin and corticosterone levels were monitored. Although metabolic disturbances induced by the excess intake of fat are assumed to cause depression, the relationship underlying dysfunctional adipose tissue, stress hormone release, and excitatory metabolism has not been fully understood yet. Four-week-old male C57BL/6 mice were separated into a HFD-fed group (n = 8) and low-fat diet-fed group (n = 8)...
December 20, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29249286/neurotransmitter-funneling-optimizes-glutamate-receptor-kinetics
#11
Alvin Yu, Héctor Salazar, Andrew J R Plested, Albert Y Lau
Ionotropic glutamate receptors (iGluRs) mediate neurotransmission at the majority of excitatory synapses in the brain. Little is known, however, about how glutamate reaches the recessed binding pocket in iGluR ligand-binding domains (LBDs). Here we report the process of glutamate binding to a prototypical iGluR, GluA2, in atomistic detail using unbiased molecular simulations. Charged residues on the LBD surface form pathways that facilitate glutamate binding by effectively reducing a three-dimensional diffusion process to a spatially constrained, two-dimensional one...
December 12, 2017: Neuron
https://www.readbyqxmd.com/read/29249203/characterization-of-excitatory-synaptic-transmission-in-the-anterior-cingulate-cortex-of-adult-tree-shrew
#12
Xu-Hui Li, Qian Song, Qi-Yu Chen, Jing-Shan Lu, Tao Chen, Min Zhuo
The tree shrew, as a primate-like animal model, has been used for studying high brain functions such as social emotion and spatial learning memory. However, little is known about the excitatory synaptic transmission in cortical brain areas of the tree shrew. In the present study, we have characterized the excitatory synaptic transmission and intrinsic properties of pyramidal neurons in the anterior cingulate cortex (ACC) of the adult tree shrew, a key cortical region for pain perception and emotion. We found that glutamate is the major excitatory transmitter for fast synaptic transmission...
December 18, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29237242/enhanced-cognition-and-dysregulated-hippocampal-synaptic-physiology-in-mice-with-a-heterozygous-deletion-of-psd-95
#13
Alexa E Horner, Catherine L McLaughlin, Nurudeen O Afinowi, Timothy J Bussey, Lisa M Saksida, Noboru H Komiyama, Seth G N Grant, Maksym V Kopanitsa
PSD-95 is one of the most abundant proteins of the postsynaptic density of excitatory synapses. It functions as the backbone of protein supercomplexes that mediate signalling between membrane glutamate receptors and intracellular pathways. Homozygous deletion of the Dlg4 gene encoding PSD-95 was previously found to cause a profound impairment in operant and Pavlovian conditioning in Dlg4-/- mice studied in touchscreen chambers that precluded evaluation of PSD-95's role in shaping more subtle forms of learning and memory...
December 13, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29230395/thc-treatment-alters-glutamate-receptor-gene-expression-in-human-stem-cell-derived-neurons
#14
Ifeanyi V Obiorah, Hamza Muhammad, Khalifa Stafford, Erin K Flaherty, Kristen J Brennand
Given the cognitive and behavioral effects following in utero Δ9-tetrahydrocannabinol (THC) exposure that have been reported in humans and rodents, it is critical to understand the precise consequences of THC on developing human neurons. Here, we utilize excitatory neurons derived from human-induced pluripotent stem cells (hiPSCs), and report that in vitro THC exposure reduced expression of glutamate receptor subunit genes (GRIA1, GRIA2, GRIN2A, and GRIN2B). By expanding these studies across hiPSC-derived neurons from individuals with a variety of genotypes, we believe that a hiPSC-based model will facilitate studies of the interaction of THC exposure and the genetic risk factors underlying neuropsychiatric disease vulnerability...
November 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/29229705/proteolytic-processing-of-neurexins-by-presenilins-sustains-synaptic-vesicle-release
#15
Emilia Servián-Morilla, Estefanía Robles-Lanuza, Ana C Sánchez-Hidalgo, Rafael J Camacho-Garcia, Juan A Paez-Gomez, Fabiola Mavillard, Carlos A Saura, Amalia Martinez-Mir, Francisco G Scholl
Proteolytic processing of synaptic adhesion components can accommodate the function of synapses to activity-dependent changes. The adhesion system formed by Neurexins (Nrxns) and Neuroligins (Nlgns) bi-directionally orchestrate the function of pre- and postsynaptic terminals. Previous studies have shown that Presenilins (PS), components of the gamma-secretase complex frequently mutated in familial Alzheimer's disease, clear from glutamatergic terminals the accumulation of Neurexin C-terminal fragments (Nrxn-CTF) generated by ectodomain shedding...
December 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29228686/dl-3n-butylphthalide-reduces-epileptiform-activity-through-glua2-lacking-calcium-permeable-ampars-in-epilepsy-models
#16
Qin Yang, Yi-Da Hu, Xue-Feng Wang, Fang-Shuo Zheng
Epilepsy is the most prevalent chronic neurological disorder, and its pathological mechanism indicates that an imbalance between excitatory and inhibitory neurotransmission leads to neuronal hyperexcitability. Previous studies have suggested that dl-3n-butylphthalide (NBP) regulates the excitatory neurotransmitter glutamate in the brains of epileptic mice, however, the mechanisms are unknown. We investigated behavioral and electrophysiological factors in rats using NBP. In an in vivo pentylenetetrazole (PTZ)-induced epileptic seizure animal model, NBP decreased the generalized tonic-clonic seizure (GTCS) severity...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29224956/bidirectional-shift-of-group-iii-metabotropic-glutamate-receptor-mediated-synaptic-depression-in-the-epileptic-hippocampus
#17
Fabian Dammann, Timo Kirschstein, Xiati Guli, Steffen Müller, Katrin Porath, Marco Rohde, Tursonjan Tokay, Rüdiger Köhling
A common function of group III metabotropic glutamate receptors (mGluRs) located at the presynaptic site of a glutamatergic synapse is synaptic depression. Here, we studied synaptic depression mediated by group III mGluR activation at Schaffer collateral-CA1 (SC-CA1) synapses and associational-commissural-CA3 (AC-CA3) synapses by recording field excitatory postsynaptic potentials in the in vitro brain slice preparation. In order to gauge the impact of synaptic depression in chronically epileptic tissue, we compared rats after pilocarpine-induced status epilepticus (post-SE) with control animals...
December 7, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/29223589/breakthroughs-in-neuroactive-steroid-drug-discovery
#18
REVIEW
Maria-Jesus Blanco, Daniel La, Quinn Coughlin, Caitlin A Newman, Andrew M Griffin, Boyd L Harrison, Francesco G Salituro
Endogenous and synthetic neuroactive steroids (NASs) or neurosteroids are effective modulators of multiple signaling pathways including receptors for the γ-aminobutyric acid A (GABAA) and glutamate, in particular N-methyl-d-aspartate (NMDA). These receptors are the major inhibitory and excitatory neurotransmitters in the central nervous system (CNS), and there is growing evidence suggesting that dysregulation of neurosteroid production plays a role in numerous neurological disorders. The significant unmet medical need for treatment of CNS disorders has increased the interest for these types of compounds...
December 2, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29212793/pacap-6-38-or-kynurenate-microinjections-into-the-rvlm-prevent-development-of-sympathetic-long-term-facilitation-following-acute-intermittent-hypoxia
#19
Zohra M Kakall, Paul M Pilowsky, Melissa Mj Farnham
BACKGROUND AND PURPOSE: Intermittent hypoxia causes a persistent increase in sympathetic activity, which progresses to hypertension in chronic conditions such as obstructive sleep apnea (OSA). Pituitary adenylate cyclase activating polypeptide (PACAP) is an excitatory neurotransmitter that causes long-lasting sympathetic excitation. We aimed to determine if intermittent activation of the rostral ventrolateral medulla (RVLM) causes PACAP-mediated elevation of sympathetic nerve activity (sSNA), termed sympathetic long-term facilitation (sLTF)...
December 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29204679/gestational-exposure-to-inorganic-arsenic-ias3-alters-glutamate-disposition-in-the-mouse-hippocampus-and-ionotropic-glutamate-receptor-expression-leading-to-memory-impairment
#20
Janikua Nelson-Mora, Martha L Escobar, Luis Rodríguez-Durán, Lourdes Massieu, Teresa Montiel, Verónica M Rodríguez, Karina Hernández-Mercado, María E Gonsebatt
Early life exposure to environmental pollutants and toxic chemicals has been linked to learning and behavioral alterations in children. iAs exposure is associated with different types neurological disorders such as memory and learning impairment. iAs is methylated in the brain by the arsenic III-methyltransferase in a process that requires glutathione (GSH). The xCT-antiporter cell membrane transporter participates in the influx of cystine for GSH synthesis in exchange for glutamate in a 1:1 ratio. In CD-1 mice gestationally exposed to 20 ppm of sodium arsenite in drinking water, we have previously observed up-regulation of xCT in the male mouse hippocampus which caused glutamatergic synapse alterations affecting learning and memory processes...
December 4, 2017: Archives of Toxicology
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