100 results match your criteria modulate ampar


NMDA and AMPA Receptor Autoantibodies in Brain Disorders: From Molecular Mechanisms to Clinical Features.

Cells 2021 Jan 5;10(1). Epub 2021 Jan 5.

Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.

The role of autoimmunity in central nervous system (CNS) disorders is rapidly expanding. In the last twenty years, different types of autoantibodies targeting subunits of ionotropic glutamate receptors have been found in a variety of patients affected by brain disorders. Several of these antibodies are directed against NMDA receptors (NMDAR), mostly in autoimmune encephalitis, whereas a growing field of research has identified antibodies against AMPA receptor (AMPAR) subunits in patients with different types of epilepsy or frontotemporal dementia. 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

Dopamine D1 and Glutamate Receptors Co-operate With Brain-Derived Neurotrophic Factor (BDNF) and TrkB to Modulate ERK Signaling in Adult Striatal Slices.

Front Cell Neurosci 2020 16;14:564106. Epub 2020 Nov 16.

Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom.

In the striatum, the input nucleus of the basal ganglia, the extracellular-signal-regulated kinase (ERK) pathway, necessary for various forms of behavioral plasticity, is triggered by the combined engagement of dopamine D1 and ionotropic glutamate receptors. In this study, we investigated the potential crosstalk between glutamatergic, dopaminergic, and brain-derived neurotrophic factor (BDNF)-TrkB inputs to ERK cascade by using an model of mouse striatal slices. Our results confirmed that the concomitant stimulation of D1 and glutamate receptors is necessary to activate ERK in striatal medium spiny neurons (MSNs). Read More

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November 2020

AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF.

Cell Rep 2020 11;33(5):108329

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, University of Massachusetts School of Medicine, Worcester, MA 01655, USA; Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:

The regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking affects multiple brain functions, such as learning and memory. We have previously shown that Thorase plays an important role in the internalization of AMPARs from the synaptic membrane. Here, we show that N-methyl-d-aspartate receptor (NMDAR) activation leads to increased S-nitrosylation of Thorase and N-ethylmaleimide-sensitive factor (NSF). Read More

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November 2020

Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking.

J Cell Biol 2020 10;219(10)

Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Spain.

Carnitine palmitoyltransferase 1C (CPT1C) is a sensor of malonyl-CoA and is located in the ER of neurons. AMPA receptors (AMPARs) mediate fast excitatory neurotransmission in the brain and play a key role in synaptic plasticity. In the present study, we demonstrate across different metabolic stress conditions that modulate malonyl-CoA levels in cortical neurons that CPT1C regulates the trafficking of the major AMPAR subunit, GluA1, through the phosphatidyl-inositol-4-phosphate (PI(4)P) phosphatase SAC1. Read More

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October 2020

D1 receptors in the anterior cingulate cortex modulate basal mechanical sensitivity threshold and glutamatergic synaptic transmission.

Mol Brain 2020 09 5;13(1):121. Epub 2020 Sep 5.

Department of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5, Canada.

The release of dopamine (DA) into target brain areas is considered an essential event for the modulation of many physiological effects. While the anterior cingulate cortex (ACC) has been implicated in pain related behavioral processes, DA modulation of synaptic transmission within the ACC and pain related phenotypes remains unclear. Here we characterized a Crispr/Cas9 mediated somatic knockout of the D1 receptor (D1R) in all neuronal subtypes of the ACC and find reduced mechanical thresholds, without affecting locomotion and anxiety. Read More

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September 2020

Reactive Oxygen Species Modulate Activity-Dependent AMPA Receptor Transport in .

J Neurosci 2020 09 26;40(39):7405-7420. Epub 2020 Aug 26.

Department of Biomedical Science, Colorado State University, Fort Collins, Colorado 80523

The AMPA subtype of synaptic glutamate receptors (AMPARs) plays an essential role in cognition. Their function, numbers, and change at synapses during synaptic plasticity are tightly regulated by neuronal activity. Although we know that long-distance transport of AMPARs is essential for this regulation, we do not understand the associated regulatory mechanisms of it. Read More

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September 2020

Characterizing the binding and function of TARP γ8-selective AMPA receptor modulators.

J Biol Chem 2020 10 3;295(43):14565-14577. Epub 2020 Aug 3.

Neurobiology Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom. Electronic address:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA)-type glutamate receptors (AMPARs) are the predominant excitatory neurotransmitter receptors in the brain, where they mediate synaptic transmission and plasticity. Excessive AMPAR activation leads to diseases such as epilepsy. AMPAR properties are modulated by auxiliary proteins and foremost by the transmembrane AMPAR regulatory proteins (TARPs). Read More

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October 2020

Modulation of information processing by AMPA receptor auxiliary subunits.

J Physiol 2021 01 24;599(2):471-483. Epub 2020 Jul 24.

Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

AMPA-type glutamate receptors (AMPARs) are key molecules of neuronal communication in our brain. The discovery of AMPAR auxiliary subunits, such as proteins of the TARP, CKAMP and CNIH families, fundamentally changed our understanding of how AMPAR function is regulated. Auxiliary subunits control almost all aspects of AMPAR function in the brain. Read More

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January 2021

AMPAR/TARP stoichiometry differentially modulates channel properties.

Elife 2020 05 26;9. Epub 2020 May 26.

Laboratori de Neurofisiologia, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.

AMPARs control fast synaptic communication between neurons and their function relies on auxiliary subunits, which importantly modulate channel properties. Although it has been suggested that AMPARs can bind to TARPs with variable stoichiometry, little is known about the effect that this stoichiometry exerts on certain AMPAR properties. Here we have found that AMPARs show a clear stoichiometry-dependent modulation by the prototypical TARP γ2 although the receptor still needs to be fully saturated with γ2 to show some typical TARP-induced characteristics (i. Read More

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AMPAR Auxiliary Protein SHISA6 Facilitates Purkinje Cell Synaptic Excitability and Procedural Memory Formation.

Cell Rep 2020 04;31(2):107515

Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, the Netherlands; Netherlands Institute for Neuroscience, 1105 CA Amsterdam, the Netherlands. Electronic address:

The majority of excitatory postsynaptic currents in the brain are gated through AMPA-type glutamate receptors, the kinetics and trafficking of which can be modulated by auxiliary proteins. It remains to be elucidated whether and how auxiliary proteins can modulate synaptic function to contribute to procedural memory formation. In this study, we report that the AMPA-type glutamate receptor (AMPAR) auxiliary protein SHISA6 (CKAMP52) is expressed in cerebellar Purkinje cells, where it co-localizes with GluA2-containing AMPARs. Read More

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Inactivation of endopeduncular nucleus impaired fear conditioning and hippocampal synaptic plasticity in rats.

Neurobiol Learn Mem 2020 09 1;173:107224. Epub 2020 Apr 1.

Department of Basic Medicine, Medical School, Kunming University of Science and Technology, Kunming, Yunnan 650550, China. Electronic address:

The internal globus pallidus (GPi) is one part of basal ganglion nucleuses which play fundamental role in motor function. Recent studies indicated that GPi could modulate emotional processing and learning, but the possible mechanism remains still unknown. In this study, the effects of endopeduncular nucleus (EP, a rodent homolog of GPi) on fear conditioning were tested in rats. Read More

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September 2020

Reduction of AMPA receptor activity on mature oligodendrocytes attenuates loss of myelinated axons in autoimmune neuroinflammation.

Sci Adv 2020 01 8;6(2):eaax5936. Epub 2020 Jan 8.

Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Glutamate dysregulation occurs in multiple sclerosis (MS), but whether excitotoxic mechanisms in mature oligodendrocytes contribute to demyelination and axonal injury is unexplored. Although current treatments modulate the immune system, long-term disability ensues, highlighting the need for neuroprotection. Glutamate is elevated before T2-visible white matter lesions appear in MS. Read More

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January 2020

Phase Separation-Mediated TARP/MAGUK Complex Condensation and AMPA Receptor Synaptic Transmission.

Neuron 2019 11 3;104(3):529-543.e6. Epub 2019 Sep 3.

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address:

Transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs) modulate AMPAR synaptic trafficking and transmission via disc-large (DLG) subfamily of membrane-associated guanylate kinases (MAGUKs). Despite extensive studies, the molecular mechanism governing specific TARP/MAGUK interaction remains elusive. Using stargazin and PSD-95 as the representatives, we discover that the entire tail of stargazin (Stg_CT) is required for binding to PSD-95. Read More

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November 2019

Inhibition and assessment of the biophysical gating properties of GluA2 and GluA2/A3 AMPA receptors using curcumin derivatives.

PLoS One 2019 27;14(8):e0221132. Epub 2019 Aug 27.

Department of Chemistry, Faculty of Science, An-Najah National University, Nablus, Palestine.

The development of efficacious and safe drugs for the treatment of neurological diseases related to glutamate toxicity has been a focus in neuropharmacological research. Specifically, discovering antagonists to modulate the activity and kinetics of AMPA receptors, which are the fastest ligand-gated ion channels involved in excitatory neurotransmission in response to glutamate. Thus, the current study investigated novel curcumin derivatives on the biophysical properties of AMPA receptors, specifically on the homomeric GluA2 and the heteromeric GluA2/A3 subunits and assessed for inhibitory actions. Read More

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Enhanced mGlu5 Signaling in Excitatory Neurons Promotes Rapid Antidepressant Effects via AMPA Receptor Activation.

Neuron 2019 10 13;104(2):338-352.e7. Epub 2019 Aug 13.

Department of Stereotactic and Functional Neurosurgery, Medical Center - University Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany; Department for Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 5, 79104 Freiburg, Germany. Electronic address:

Conventional antidepressants have limited efficacy and many side effects, highlighting the need for fast-acting and specific medications. Induction of the synaptic protein Homer1a mediates the effects of different antidepressant treatments, including the rapid action of ketamine and sleep deprivation (SD). We show here that mimicking Homer1a upregulation via intravenous injection of cell-membrane-permeable TAT-Homer1a elicits rapid antidepressant effects in various tests. Read More

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October 2019

Chronic stress induces cell type-selective transcriptomic and electrophysiological changes in the bed nucleus of the stria terminalis.

Neuropharmacology 2019 05 14;150:80-90. Epub 2019 Mar 14.

Department of Psychiatry, Emory University, and Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes NPRC, 954 Gatewood Road, Atlanta, GA, 30329, USA. Electronic address:

Distinct regions and cell types in the anterolateral group of the bed nucleus of the stria terminalis (BNST) act to modulate anxiety in opposing ways. A history of chronic stress increases anxiety-like behavior with lasting electrophysiological effects on the BNST. However, the opposing circuits within the BNST suggest that stress may have differential effects on the individual cell types that comprise these circuits to shift the balance to favor anxiogenesis. Read More

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CA1 Neurons Acquire Rett Syndrome Phenotype After Brief Activation of Glutamatergic Receptors: Specific Role of mGluR1/5.

Front Cell Neurosci 2018 17;12:363. Epub 2018 Oct 17.

CNMPB (Centre for Nanoscale Microscopy and Molecular Physiology of the Brain, Cluster of Excellence 171, DFG Research Center 103), Institute of Neuro and Sensory Physiology, University of Göttingen, Göttingen, Germany.

Rett syndrome (RTT) is a neurological disorder caused by the mutation of the X-linked MECP2 gene. The neurophysiological hallmark of the RTT phenotype is the hyperexcitability of neurons made responsible for frequent epileptic attacks in the patients. Increased excitability in RTT might stem from impaired glutamate handling in RTT and its long-term consequences that has not been examined quantitatively. Read More

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October 2018

The Regulation of AMPA Receptor Endocytosis by Dynamic Protein-Protein Interactions.

Front Cell Neurosci 2018 11;12:362. Epub 2018 Oct 11.

Centre for Synaptic Plasticity and School of Biochemistry, University of Bristol, Bristol, United Kingdom.

The precise regulation of AMPA receptor (AMPAR) trafficking in neurons is crucial for excitatory neurotransmission, synaptic plasticity and the consequent formation and modification of neural circuits during brain development and learning. Clathrin-mediated endocytosis (CME) is an essential trafficking event for the activity-dependent removal of AMPARs from the neuronal plasma membrane, resulting in a reduction in synaptic strength known as long-term depression (LTD). The regulated AMPAR endocytosis that underlies LTD is caused by specific modes of synaptic activity, most notably stimulation of NMDA receptors (NMDARs) and metabotropic glutamate receptors (mGluRs). Read More

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October 2018

mGluR1-Dependent Long Term Depression in Rodent Midbrain Dopamine Neurons Is Regulated by Neuregulin 1/ErbB Signaling.

Front Mol Neurosci 2018 1;11:346. Epub 2018 Oct 1.

Department of Experimental Neuroscience, IRCCS Santa Lucia Foundation, Rome, Italy.

Increasing evidence demonstrates that the neurotrophic factor Neuregulin 1 (NRG1) and its receptors, ErbB tyrosine kinases, modulate midbrain dopamine (DA) transmission. We have previously reported that NRG1/ErbB signaling is essential for proper metabotropic glutamate receptors 1 (mGluR1) functioning in midbrain DA neurons, thus the functional interaction between ErbB receptors and mGluR1 regulates neuronal excitation and striatal DA release. While it is widely recognized that mGluR1 play a pivotal role in long-term modifications of synaptic transmission in several brain areas, specific mGluR1-dependent forms of synaptic plasticity in substantia nigra pars compacta (SNpc) DA neurons have not been described yet. Read More

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October 2018

Kainate Receptors Play a Role in Modulating Synaptic Transmission in the Olfactory Bulb.

Neuroscience 2018 11 11;391:25-49. Epub 2018 Sep 11.

Program in Neuroscience, Florida State University, Tallahassee, FL, United States; Department of Biological Science, Florida State University, Tallahassee, FL, United States. Electronic address:

Glutamate is the neurotransmitter used at most excitatory synapses in the mammalian brain, including those in the olfactory bulb (OB). There, ionotropic glutamate receptors including N-methyl-d-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) play a role in processes such as reciprocal inhibition and glomerular synchronization. Kainate receptors (KARs) represent another type of ionotropic glutamate receptor, which are composed of five (GluK1-GluK5) subunits. Read More

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November 2018

SAP102 regulates synaptic AMPAR function through a CNIH-2-dependent mechanism.

J Neurophysiol 2018 10 1;120(4):1578-1586. Epub 2018 Aug 1.

Picower Institute for Learning and Memory, Massachusetts Institute of Technology , Cambridge, Massachusetts.

The postsynaptic density (PSD)-95-like, disk-large (DLG) membrane-associated guanylate kinase (PSD/DLG-MAGUK) family of proteins scaffold α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) complexes to the postsynaptic compartment and are postulated to orchestrate activity-dependent modulation of synaptic AMPAR functions. SAP102 is a key member of this family, present from early development, before PSD-95 and PSD-93, and throughout life. Here we investigate the role of SAP102 in synaptic transmission using a cell-restricted molecular replacement strategy, where SAP102 is expressed against the background of acute knockdown of endogenous PSD-95. Read More

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October 2018

Neuronal Activity and Intracellular Calcium Levels Regulate Intracellular Transport of Newly Synthesized AMPAR.

Cell Rep 2018 07;24(4):1001-1012.e3

University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France. Electronic address:

Regulation of AMPA receptor (AMPAR) trafficking is a key modulator of excitatory synaptic transmission; however, intracellular vesicular transport of newly synthesized AMPARs has been little studied due to technical limitations. By combining molecular tools with imaging strategies in cultured rat hippocampal neurons, we found that vesicles containing newly synthesized, GluA1-subunit-containing AMPARs are transported antero- and retrogradely at a mean speed of 1.5 μm. Read More

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AMPA receptor trafficking and its role in heterosynaptic plasticity.

Sci Rep 2018 07 9;8(1):10349. Epub 2018 Jul 9.

Center for Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo, SP, Brazil.

Historically, long-term potentiation (LTP) and long-term depression (LTD), the best-characterized forms of long-term synaptic plasticity, are viewed as experience-dependent and input-specific processes. However, cumulative experimental and theoretical data have demonstrated that LTP and LTD can promote compensatory alterations in non-stimulated synapses. In this work, we have developed a computational model of a tridimensional spiny dendritic segment to investigate the role of AMPA receptor (AMPAR) trafficking during synaptic plasticity at specific synapses and its consequences for the populations of AMPAR at nearby synapses. Read More

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AMPA receptor complex constituents: Control of receptor assembly, membrane trafficking and subcellular localization.

Mol Cell Neurosci 2018 09 26;91:67-75. Epub 2018 May 26.

Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. Electronic address:

Fast excitatory transmission at synapses of the central nervous system is mainly mediated by AMPA receptors (AMPARs). Synaptic AMPAR number and function correlates with synaptic strength. AMPARs are thus key proteins of activity-dependent plasticity in neuronal communication. Read More

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September 2018

Mental Illnesses-Associated Fxr1 and Its Negative Regulator Gsk3β Are Modulators of Anxiety and Glutamatergic Neurotransmission.

Front Mol Neurosci 2018 12;11:119. Epub 2018 Apr 12.

Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.

Genetic variants of the fragile X mental retardation syndrome-related protein 1 ( have been associated to mood regulation, schizophrenia, and bipolar disorders. Nonetheless, genetic association does not indicate a functional link of a given gene to neuronal activity and associated behaviors. In addition, interaction between multiple genes is often needed to sculpt complex traits such as behavior. Read More

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Circadian rhythm and sleep-wake systems share the dynamic extracellular synaptic milieu.

Neurobiol Sleep Circadian Rhythms 2018 Jun 17;5:15-36. Epub 2018 Apr 17.

NeuroNET Research Center, University of Tennessee, Knoxville, TN, USA.

The mammalian circadian and sleep-wake systems are closely aligned through their coordinated regulation of daily activity patterns. Although they differ in their anatomical organization and physiological processes, they utilize overlapping regulatory mechanisms that include an assortment of proteins and molecules interacting within the extracellular space. These extracellular factors include proteases that interact with soluble proteins, membrane-attached receptors and the extracellular matrix; and cell adhesion molecules that can form complex scaffolds connecting adjacent neurons, astrocytes and their respective intracellular cytoskeletal elements. Read More

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Inhibition of Cgkii Suppresses Seizure Activity and Hippocampal Excitation by Regulating the Postsynaptic Delivery of Glua1.

Cell Physiol Biochem 2018 21;46(1):160-177. Epub 2018 Mar 21.

Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, China.

Background/aims: The imbalance between excitation and inhibition is a defining feature of epilepsy. GluA1 is an AMPA receptor subunit that can strengthen excitatory synaptic transmission when upregulated in the postsynaptic membrane, which has been implicated in the pathogenesis of epilepsy. cGKII, a cGMP-dependent protein kinase, regulates the GluA1 levels at the plasma membrane. Read More

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Mesenchymal Stem Cell Protection of Neurons against Glutamate Excitotoxicity Involves Reduction of NMDA-Triggered Calcium Responses and Surface GluR1, and Is Partly Mediated by TNF.

Int J Mol Sci 2018 Feb 25;19(3). Epub 2018 Feb 25.

Laboratory of Molecular Genetics, Department of Immunology, Hellenic Pasteur Institute, 127 Vasilissis Sophias Ave., 11521 Athens, Greece.

Mesenchymal stem cells (MSC) provide therapeutic effects in experimental CNS disease models and show promise as cell-based therapies for humans, but their modes of action are not well understood. We previously show that MSC protect rodent neurons against glutamate excitotoxicity in vitro, and in vivo in an epilepsy model. Neuroprotection is associated with reduced NMDA glutamate receptor (NMDAR) subunit expression and neuronal glutamate-induced calcium (Ca) responses, and increased expression of stem cell-associated genes. Read More

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February 2018

A Unique Homeostatic Signaling Pathway Links Synaptic Inactivity to Postsynaptic mTORC1.

J Neurosci 2018 02 8;38(9):2207-2225. Epub 2018 Jan 8.

Neuroscience Graduate Program,

mTORC1-dependent translational control plays a key role in several enduring forms of synaptic plasticity such as long term potentiation (LTP) and mGluR-dependent long term depression. Recent evidence demonstrates an additional role in regulating synaptic homeostasis in response to inactivity, where dendritic mTORC1 serves to modulate presynaptic function via retrograde signaling. Presently, it is unclear whether LTP and homeostatic plasticity use a common route to mTORC1-dependent signaling or whether each engage mTORC1 through distinct pathways. Read More

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February 2018