1,855 results match your criteria ampar function

Regulation of Synaptic Transmission and Plasticity by Protein Phosphatase 1.

J Neurosci 2021 Apr;41(14):3040-3050

Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642

Protein phosphatases, by counteracting protein kinases, regulate the reversible phosphorylation of many substrates involved in synaptic plasticity, a cellular model for learning and memory. A prominent phosphatase regulating synaptic plasticity and neurologic disorders is the serine/threonine protein phosphatase 1 (PP1). PP1 has three isoforms (α, β, and γ, encoded by three different genes), which are regulated by a vast number of interacting subunits that define their enzymatic substrate specificity. Read More

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A Role for Transmembrane Protein 16C/Slack Impairment in Excitatory Nociceptive Synaptic Plasticity in the Pathogenesis of Remifentanil-induced Hyperalgesia in Rats.

Neurosci Bull 2021 Mar 29. Epub 2021 Mar 29.

Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin, 300052, China.

Remifentanil is widely used to control intraoperative pain. However, its analgesic effect is limited by the generation of postoperative hyperalgesia. In this study, we investigated whether the impairment of transmembrane protein 16C (TMEM16C)/Slack is required for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) activation in remifentanil-induced postoperative hyperalgesia. Read More

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Missense mutation of Fmr1 results in impaired AMPAR-mediated plasticity and socio-cognitive deficits in mice.

Nat Commun 2021 03 10;12(1):1557. Epub 2021 Mar 10.

Université Côte d'Azur, Inserm, CNRS, IPMC, Valbonne, France.

Fragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and the best-described monogenic cause of autism. CGG-repeat expansion in the FMR1 gene leads to FMR1 silencing, loss-of-expression of the Fragile X Mental Retardation Protein (FMRP), and is a common cause of FXS. Missense mutations in the FMR1 gene were also identified in FXS patients, including the recurrent FMRP-R138Q mutation. Read More

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P2X4 receptor in the dorsal horn contributes to BDNF/TrkB and AMPA receptor activation in the pathogenesis of remifentanil-induced postoperative hyperalgesia in rats.

Neurosci Lett 2021 04 24;750:135773. Epub 2021 Feb 24.

Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin, 300052, China. Electronic address:

The mechanism underlying the high incidence of remifentanil-induced postoperative hyperalgesia is unclear. Also, no effective prevention method exists. Inflammatory pain-related studies showed that P2X4 purinergic receptors (P2X4Rs) in the dorsal horn of the spinal cord and dorsal root ganglia are essential for maintaining allodynia caused by inflammation. Read More

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The WD40-Repeat Protein WDR-20 and the Deubiquitinating Enzyme USP-46 Promote Cell Surface Levels of Glutamate Receptors.

J Neurosci 2021 Apr 23;41(14):3082-3093. Epub 2021 Feb 23.

Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts 02111

Reversible modification of AMPA receptors (AMPARs) with ubiquitin regulates receptor levels at synapses and controls synaptic strength. The conserved deubiquitinating enzyme (DUB) ubiquitin-specific protease-46 (USP-46) removes ubiquitin from AMPARs and protects them from degradation in both and mammals. Although DUBs are critical for diverse physiological processes, the mechanisms that regulate DUBs, especially in the nervous system, are not well understood. Read More

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Selective co-activation of α7- and α4β2-nicotinic acetylcholine receptors reverses beta-amyloid-induced synaptic dysfunction.

J Biol Chem 2021 Feb 8:100402. Epub 2021 Feb 8.

Molecular, Cellular and Integrative Neurosciences Program; Department of Biomedical Sciences, Colorado State University, CO, 80523. Electronic address:

Beta-amyloid (Aβ) has been recognized as an early trigger in the pathogenesis of Alzheimer's disease (AD) leading to synaptic and cognitive impairments. Aβ can alter neuronal signaling through interactions with nicotinic acetylcholine receptors (nAChRs), contributing to synaptic dysfunction in AD. The three major nAChR subtypes in the hippocampus are composed of α7-, α4β2-, and α3β4-nAChRs. Read More

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February 2021

Spinal AMPA receptors: Amenable players in central sensitization for chronic pain therapy?

Channels (Austin) 2021 Dec;15(1):284-297

Department of Sensory Signalling, Bogomoletz Institute of Physiology , Kyiv, Ukraine.

The activity-dependent trafficking of AMPA receptors (AMPAR) mediates synaptic strength and plasticity, while the perturbed trafficking of the receptors of different subunit compositions has been linked to memory impairment and to causing neuropathology. In the spinal cord, nociceptive-induced changes in AMPAR trafficking determine the central sensitization of the dorsal horn (DH): changes in AMPAR subunit composition compromise the balance between synaptic excitation and inhibition, rendering interneurons hyperexcitable to afferent inputs, and promoting Ca influx into the DH neurons, thereby amplifying neuronal hyperexcitability. The DH circuits become over-excitable and carry out aberrant sensory processing; this causes an increase in pain sensation in central sensory pathways, giving rise to chronic pain syndrome. Read More

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December 2021

VER/VEGF receptors regulate AMPA receptor surface levels and glutamatergic behavior.

PLoS Genet 2021 Feb 9;17(2):e1009375. Epub 2021 Feb 9.

Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

Several intracellular trafficking pathways contribute to the regulation of AMPA receptor (AMPAR) levels at synapses and the control of synaptic strength. While much has been learned about these intracellular trafficking pathways, a major challenge is to understand how extracellular factors, such as growth factors, neuropeptides and hormones, impinge on specific AMPAR trafficking pathways to alter synaptic function and behavior. Here, we identify the secreted ligand PVF-1 and its cognate VEGF receptor homologs, VER-1 and VER-4, as regulators of glutamate signaling in C. Read More

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February 2021

Ligand-directed two-step labeling to quantify neuronal glutamate receptor trafficking.

Nat Commun 2021 02 5;12(1):831. Epub 2021 Feb 5.

Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya, 464-8603, Japan.

The regulation of glutamate receptor localization is critical for development and synaptic plasticity in the central nervous system. Conventional biochemical and molecular biological approaches have been widely used to analyze glutamate receptor trafficking, especially for α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate-type glutamate receptors (AMPARs). However, conflicting findings have been reported because of a lack of useful tools for analyzing endogenous AMPARs. Read More

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February 2021

Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation.

Sci Rep 2021 Feb 4;11(1):3163. Epub 2021 Feb 4.

Department of Biomedical Engineering, Johns Hopkins University, 379 Miller Res. Bldg, Baltimore, MD, 21205, USA.

The development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Read More

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February 2021

Stress undermines reward-guided cognitive performance through synaptic depression in the lateral habenula.

Neuron 2021 03 2;109(6):947-956.e5. Epub 2021 Feb 2.

The Department of Fundamental Neuroscience, The University of Lausanne, 1005 Lausanne, Switzerland; Inserm, UMR-S 839, 75005 Paris, France. Electronic address:

Weighing alternatives during reward pursuit is a vital cognitive computation that, when disrupted by stress, yields aspects of neuropsychiatric disorders. To examine the neural mechanisms underlying these phenomena, we employed a behavioral task in which mice were confronted by a reward and its omission (i.e. Read More

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Ca -permeable AMPA receptors and their auxiliary subunits in synaptic plasticity and disease.

J Physiol 2021 Feb 3. Epub 2021 Feb 3.

Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.

AMPA receptors are tetrameric glutamate-gated ion channels that mediate a majority of fast excitatory neurotransmission in the brain. They exist as calcium-impermeable (CI-) and calcium-permeable (CP-) subtypes, the latter of which lacks the GluA2 subunit. CP-AMPARs display an array of distinctive biophysical and pharmacological properties that allow them to be functionally identified. Read More

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February 2021

The Snail transcription factor CES-1 regulates glutamatergic behavior in C. elegans.

PLoS One 2021 2;16(2):e0245587. Epub 2021 Feb 2.

Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

Regulation of AMPA-type glutamate receptor (AMPAR) expression and function alters synaptic strength and is a major mechanism underlying synaptic plasticity. Although transcription is required for some forms of synaptic plasticity, the transcription factors that regulate AMPA receptor expression and signaling are incompletely understood. Here, we identify the Snail family transcription factor ces-1 in an RNAi screen for conserved transcription factors that regulate glutamatergic behavior in C. Read More

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February 2021

Amygdala-hippocampal innervation modulates stress-induced depressive-like behaviors through AMPA receptors.

Proc Natl Acad Sci U S A 2021 Feb;118(6)

Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory for Neuroscience, Ministry of Education/National Health Commission of People's Republic of China, IDG/McGovern Institute for Brain Research at Peking University, 100083 Beijing, People's Republic of China;

Chronic stress is one of the most critical factors in the onset of depressive disorders; hence, environmental factors such as psychosocial stress are commonly used to induce depressive-​like traits in animal models of depression. Ventral CA1 (vCA1) in hippocampus and basal lateral amygdala (BLA) are critical sites during chronic stress-induced alterations in depressive subjects; however, the underlying neural mechanisms remain unclear. Here we employed chronic unpredictable mild stress (CUMS) to model depression in mice and found that the activity of the posterior BLA to vCA1 (pBLA-vCA1) innervation was markedly reduced. Read More

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February 2021

An iPSC-based neural model of sialidosis uncovers glycolytic impairment-causing presynaptic dysfunction and deregulation of Ca dynamics.

Neurobiol Dis 2021 May 29;152:105279. Epub 2021 Jan 29.

Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. Electronic address:

Sialidosis is a neuropathic lysosomal storage disease caused by a deficiency in the NEU1 gene-encoding lysosomal neuraminidase and characterized by abnormal accumulation of undigested sialyl-oligoconjugates in systemic organs including brain. Although patients exhibit neurological symptoms, the underlying neuropathological mechanism remains unclear. Here, we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts with sialidosis and induced the differentiation into neural progenitor cells (NPCs) and neurons. Read More

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Oxidative Stress Underlies the Ischemia/Reperfusion-Induced Internalization and Degradation of AMPA Receptors.

Int J Mol Sci 2021 Jan 13;22(2). Epub 2021 Jan 13.

Department of Pharmaceutical Sciences and Molecular Medicine, Washington State University-Health Sciences, Spokane, WA 99201, USA.

Stroke is the fifth leading cause of death annually in the United States. Ischemic stroke occurs when a blood vessel supplying the brain is occluded. The hippocampus is particularly susceptible to AMPA receptor-mediated delayed neuronal death as a result of ischemic/reperfusion injury. Read More

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January 2021

Exosomes expressing neuronal autoantigens induced immune response in antibody-positive autoimmune encephalitis.

Mol Immunol 2021 03 11;131:164-170. Epub 2021 Jan 11.

Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

The immunological role of exosomes in autoimmune encephalitis (AE) remains uncharacterized and not examined. In this study we ought to determine whether exosomes are generated in AE and to define the presence of cell surface neuronal autoantigens (autoAgs) in the cargo. Exosomes were isolated from cerebrospinal fluid (CSF) from 12 patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, 8 patients with anti-gamma-aminobutyric acid-B (GABA) receptor encephalitis, 8 patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, 8 patients with anti-contactin-associated protein-like 2 (CASPR2) encephalitis, 10 patients with anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1,2 (AMPA) receptor encephalitis and 30 control individuals negative of antibodies against neuronal autoAgs. Read More

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Translational medicine of the glutamate AMPA receptor.

Proc Jpn Acad Ser B Phys Biol Sci 2021 ;97(1):1-21

Yokohama City University Graduate School of Medicine, Department of Physiology.

Psychiatric and neurological disorders severely hamper patient's quality of life. Despite their high unmet needs, the development of diagnostics and therapeutics has only made slow progress. This is due to limited evidence on the biological basis of these disorders in humans. Read More

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January 2021

Roles of palmitoylation in structural long-term synaptic plasticity.

Mol Brain 2021 01 11;14(1). Epub 2021 Jan 11.

Nencki Institute of Experimental Biology, 02-093, Warsaw, Poland.

Long-term potentiation (LTP) and long-term depression (LTD) are important cellular mechanisms underlying learning and memory processes. N-Methyl-D-aspartate receptor (NMDAR)-dependent LTP and LTD play especially crucial roles in these functions, and their expression depends on changes in the number and single channel conductance of the major ionotropic glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) located on the postsynaptic membrane. Structural changes in dendritic spines comprise the morphological platform and support for molecular changes in the execution of synaptic plasticity and memory storage. Read More

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January 2021

Cornel Iridoid Glycoside Suppresses Hyperactivity Phenotype in rTg4510 Mice through Reducing Tau Pathology and Improving Synaptic Dysfunction.

Curr Med Sci 2020 Dec 11;40(6):1031-1039. Epub 2021 Jan 11.

Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.

rTg4510 mice are transgenic mice expressing P301L mutant tau and have been developed as an animal model of tauopathies including Alzheimer's disease (AD). Besides cognitive impairments, rTg4510 mice also show abnormal hyperactivity behavior. Cornel iridoid glycoside (CIG) is an active ingredient extracted from Cornus officinalis, a traditional Chinese herb. Read More

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December 2020

The AMPAR antagonist perampanel protects the neurovascular unit against traumatic injury via regulating Sirt3.

CNS Neurosci Ther 2021 Jan 9;27(1):134-144. Epub 2021 Jan 9.

Department of Neurosurgery, The 904th Hospital of PLA, Medical School of Anhui Medical University, Wuxi, China.

Introduction: Perampanel is a highly selective and noncompetitive α-amino-3 -hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) antagonist, which has been used as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was shown to exert neuroprotective effects in hemorrhagic and ischemic stroke models via regulating blood-brain barrier (BBB) function.

Aim: Here, the protective effects of perampanel were investigated in an in vitro neurovascular unit (NVU) system established using a triple cell co-culture model (neurons, astrocytes, and brain microvascular endothelial cells) and in an in vivo traumatic brain injury (TBI) model. Read More

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January 2021

AMPAr GluA1 Phosphorylation at Serine 845 in Limbic System Is Associated with Cardiac Autonomic Tone.

Mol Neurobiol 2021 Apr 6;58(4):1859-1870. Epub 2021 Jan 6.

Center for Applied Neuroscience, University Hospital (HU), UFSC, Florianopolis, SC, Brazil.

The central autonomic network, which is connected to the limbic system structures including the amygdala (AMY) and anterior hippocampus (aHIP), regulates the sympathetic and parasympathetic modulation of visceromotor, neuroendocrine, pain, and behavior manifestations during stress responses. Heart rate variability (HRV) is useful to estimate the cardiac autonomic tone. The levels of phosphorylation on the Ser831 and Ser845 sites of the GluA1 subunit of the AMPAr (P-GluA1-Ser845 and P-GluA1-Ser831) are useful markers of synaptic plasticity. Read More

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Increased glutamate transmission onto dorsal striatum spiny projection neurons in Pink1 knockout rats.

Neurobiol Dis 2021 Mar 30;150:105246. Epub 2020 Dec 30.

Center for Neurodegeneration and Experimental Therapeutics, the University of Alabama at Birmingham, Birmingham, AL 35294, United States of America; Department of Neurology, the University of Alabama at Birmingham, Birmingham, AL 35294, United States of America; Department of Neurobiology, the University of Alabama at Birmingham, Birmingham, AL 35294, United States of America. Electronic address:

Loss-of-function PTEN Induced Kinase 1 (PINK1) mutations cause early-onset familial Parkinson's disease (PD) with similar clinical and neuropathological characteristics as idiopathic PD. While Pink1 knockout (KO) rats have mitochondrial dysfunction, locomotor deficits, and α-synuclein aggregates in several brain regions such as cerebral cortex, dorsal striatum, and substantia nigra, the functional ramifications on synaptic circuits are unknown. Using whole cell patch clamp recordings, we found a significant increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) onto striatal spiny projection neurons (SPNs) in Pink1 KO rats at ages 4 and 6 months compared to wild-type (WT) littermates, suggesting increased excitability of presynaptic neurons. Read More

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Aerobic Exercise Prevents Depression via Alleviating Hippocampus Injury in Chronic Stressed Depression Rats.

Brain Sci 2020 Dec 23;11(1). Epub 2020 Dec 23.

Physical Education Institute, Shaanxi Normal University, Xi'an 710119, China.

(1) Background: Depression is one of the overwhelming public health problems. Alleviating hippocampus injury may prevent depression development. Herein, we established the chronic unpredictable mild stress (CUMS) model and aimed to investigate whether aerobic exercise (AE) could alleviate CUMS induced depression-like behaviors and hippocampus injury. Read More

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December 2020

Src/CK2/PTEN-Mediated GluN2B and CREB Dephosphorylations Regulate the Responsiveness to AMPA Receptor Antagonists in Chronic Epilepsy Rats.

Int J Mol Sci 2020 Dec 17;21(24). Epub 2020 Dec 17.

Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon 24252, Korea.

Both α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) have been reported as targets for treatment of epilepsy. To investigate the roles and interactions of AMPAR and NMDAR in ictogenesis of epileptic hippocampus, we analyzed AMPAR antagonists (perampanel and GYKI 52466)-mediated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) regulation and glutamate ionotropic receptor NMDA type subunit 2B (GluN2B) tyrosine (Y) 1472 phosphorylation in epilepsy rats. Both perampanel and GYKI 52466 increased PTEN expression and its activity (reduced phosphorylation), concomitant with decreased activities (phosphorylations) of Src family-casein kinase 2 (CK2) signaling pathway. Read More

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December 2020

Transient Enhanced GluA2 Expression in Young Hippocampal Neurons of a Fragile X Mouse Model.

Front Synaptic Neurosci 2020 3;12:588295. Epub 2020 Dec 3.

Department of Physiology and Biophysics, University of Washington, Seattle, WA, United States.

AMPA-type glutamate receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits and play important roles in synaptic transmission and plasticity. Here, we have investigated the development of AMPAR-mediated synaptic transmission in the hippocampus of the Fmr1 knock-out (KO) mouse, a widely used model of Fragile X syndrome (FXS). FXS is the leading monogenic cause of intellectual disability and autism spectrum disorders (ASD) and it is considered a neurodevelopmental disorder. Read More

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December 2020

Iridoids from Gardeniae fructus ameliorates depression by enhancing synaptic plasticity via AMPA receptor-mTOR signaling.

J Ethnopharmacol 2021 Mar 8;268:113665. Epub 2020 Dec 8.

School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address:

Ethnopharmacological Relevance: Gardeniae fructus is a traditional Chinese herb which exerts antidepressant effect. However, its effective constituent and potential mechanism are still unknown.

Aim Of The Study: To examine whether iridoids, a type of monoterpenoids from Gardeniae fructus (IGF), exerts antidepressant effect by enhancing synaptic plasticity via AMPA receptor-mTOR signaling. Read More

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Ionotropic glutamate receptors in platelets: opposing effects and a unifying hypothesis.

Platelets 2020 Dec 7:1-11. Epub 2020 Dec 7.

Red Blood Cell Research Group, Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich , Zürich, Switzerland.

Ionotropic glutamate receptors include -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), kainate receptors (KAR), and -methyl-D-aspartate receptors (NMDAR). All function as cation channels; AMPAR and KAR are more permeable to sodium and NMDAR to calcium ions. Compared to the brain, receptor assemblies in platelets are unusual, suggesting distinctive functionalities. Read More

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December 2020

CB1 Receptor Signaling Modulates Amygdalar Plasticity during Context-Cocaine Memory Reconsolidation to Promote Subsequent Cocaine Seeking.

J Neurosci 2021 01 30;41(4):613-629. Epub 2020 Nov 30.

Department of Integrative Physiology and Neuroscience, Washington State University College of Veterinary Medicine, Pullman, Washington 99164

Contextual drug-associated memories precipitate craving and relapse in cocaine users. Such associative memories can be weakened through interference with memory reconsolidation, a process by which memories are maintained following memory retrieval-induced destabilization. We hypothesized that cocaine-memory reconsolidation requires cannabinoid type 1 receptor (CB1R) signaling based on the fundamental role of the endocannabinoid system in synaptic plasticity and emotional memory processing. Read More

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January 2021

PKN1 promotes synapse maturation by inhibiting mGluR-dependent silencing through neuronal glutamate transporter activation.

Commun Biol 2020 Nov 26;3(1):710. Epub 2020 Nov 26.

Biosignal Research Center, Kobe University, Kobe, Hyogo, 657-8501, Japan.

Abnormal metabotropic glutamate receptor (mGluR) activity could cause brain disorders; however, its regulation has not yet been fully understood. Here, we report that protein kinase N1 (PKN1), a protein kinase expressed predominantly in neurons in the brain, normalizes group 1 mGluR function by upregulating a neuronal glutamate transporter, excitatory amino acid transporter 3 (EAAT3), and supports silent synapse activation. Knocking out PKN1a, the dominant PKN1 subtype in the brain, unmasked abnormal input-nonspecific mGluR-dependent long-term depression (mGluR-LTD) and AMPA receptor (AMPAR) silencing in the developing hippocampus. Read More

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November 2020