1,394 results match your criteria ampars

EphrinB2 and GRIP1 stabilize mushroom spines during denervation-induced homeostatic plasticity.

Cell Rep 2021 Mar;34(13):108923

Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany; Max Planck Institute for Brain Research, Max von Laue Str. 4, 60438 Frankfurt am Main, Germany; Cardio-Pulmonary Institute (CPI), Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany. Electronic address:

Despite decades of work, much remains elusive about molecular events at the interplay between physiological and structural changes underlying neuronal plasticity. Here, we combined repetitive live imaging and expansion microscopy in organotypic brain slice cultures to quantitatively characterize the dynamic changes of the intracellular versus surface pools of GluA2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) across the different dendritic spine types and the shaft during hippocampal homeostatic plasticity. Mechanistically, we identify ephrinB2 and glutamate receptor interacting protein (GRIP) 1 as mediating AMPAR relocation to the mushroom spine surface following lesion-induced denervation. Read More

View Article and Full-Text PDF

Potential mechanism of GABA secretion in response to the activation of GluK1-containing kainate receptors.

Neurosci Res 2021 Mar 27. Epub 2021 Mar 27.

Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", 142290, Pushchino, Russia. Electronic address:

Hippocampal GABAergic neurons are subdivided into more than 20 subtypes that are distinguished by features and functions. We have previously described the subpopulation of GABAergic neurons, which can be identified in hippocampal cell culture by the calcium response to the application of domoic acid (DoA), an agonist of kainate receptors (KARs). Here, we investigate the features of DoA-sensitive neurons and their GABA release mechanism in response to KARs activation. Read More

View Article and Full-Text PDF

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

View Article and Full-Text PDF

Targeting redox-altered plasticity to reactivate synaptic function: A novel therapeutic strategy for cognitive disorder.

Acta Pharm Sin B 2021 Mar 24;11(3):599-608. Epub 2020 Nov 24.

Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity altering functions of key proteins, such as -methyl-d-aspartate receptor (NMDAR). Age-related cognitive disorders includes Alzheimer's disease (AD), vascular dementia (VD), and age-associated memory impairment (AAMI). Based on the critical role of NMDAR-dependent long-term potentiation (LTP) in memory, the increase of reactive oxygen species in cognitive disorders, and the sensitivity of NMDAR to the redox status, converging lines have suggested the redox-altered NMDAR-dependent plasticity might underlie the synaptic dysfunctions associated with cognitive disorders. Read More

View Article and Full-Text PDF

Membrane Remodeling by Arc/Arg3.1.

Front Mol Biosci 2021 8;8:630625. Epub 2021 Mar 8.

Department of Cell and Molecular Biology, University of Hawaii at Manoa, Honolulu, HI, United States.

The activity-regulated cytoskeletal-associated protein (Arc, also known as Arg3.1) is an immediate early gene product induced by activity/experience and required for multiple modes of synaptic plasticity. Both long-term potentiation (LTP) and long-term depression (LTD) are impaired upon Arc deletion, as well as the ability to form long-term spatial, taste and fear memories. Read More

View Article and Full-Text PDF

Decreased neuronal synaptosome associated protein 29 contributes to poststroke cognitive impairment by disrupting presynaptic maintenance.

Theranostics 2021 4;11(10):4616-4636. Epub 2021 Mar 4.

Department of Neurobiology, Department of Physiology and Pathophysiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China.

Poststroke cognitive impairments are common in stroke survivors, and pose a high risk of incident dementia. However, the cause of these cognitive impairments is obscure and required an investigation. Oxygen-glucose deprivation (OGD) model and middle cerebral artery occlusion (MCAO) model were used to imitate or acute cerebral ischemia, respectively. Read More

View Article and Full-Text PDF

Synaptic Adaptations at the Rostromedial Tegmental Nucleus Underlie Individual Differences in Cocaine Avoidance Behavior.

J Neurosci 2021 Mar 22. Epub 2021 Mar 22.

Department of Neurosciences, Medical University of South Carolina

Although cocaine is powerfully rewarding, not all individuals are equally prone to abusing this drug. We postulate that these differences arise in part because some individuals exhibit stronger aversive responses to cocaine that protect against cocaine seeking. Indeed, using conditioned place preference (CPP) and a runway operant cocaine self-administration task, we demonstrate that avoidance responses to cocaine vary greatly between individual "high cocaine-avoider" and "low cocaine-avoider" rats. Read More

View Article and Full-Text PDF

An optimized CRISPR/Cas9 approach for precise genome editing in neurons.

Elife 2021 Mar 10;10. Epub 2021 Mar 10.

Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States.

The efficient knock-in of large DNA fragments to label endogenous proteins remains especially challenging in non-dividing cells such as neurons. We developed argeted nock-n with wo (TKIT) guides as a novel CRISPR/Cas9 based approach for efficient, and precise, genomic knock-in. Through targeting non-coding regions TKIT is resistant to INDEL mutations. Read More

View Article and Full-Text PDF

Long-Term Shaping of Corticostriatal Synaptic Activity by Acute Fasting.

Int J Mol Sci 2021 Feb 15;22(4). Epub 2021 Feb 15.

Laboratorio di Neurofisiologia Sperimentale e del Comportamento, IRCCS Fondazione Santa Lucia c/o CERC, 00143 Rome, Italy.

Food restriction is a robust nongenic, nonsurgical and nonpharmacologic intervention known to improve health and extend lifespan in various species. Food is considered the most essential and frequently consumed natural reward, and current observations have demonstrated homeostatic responses and neuroadaptations to sustained intermittent or chronic deprivation. Results obtained to date indicate that food deprivation affects glutamatergic synapses, favoring the insertion of GluA2-lacking α-Ammino-3-idrossi-5-Metil-4-idrossazol-Propionic Acid receptors (AMPARs) in postsynaptic membranes. Read More

View Article and Full-Text PDF
February 2021

The amino-terminal domain of GluA1 mediates LTP maintenance via interaction with neuroplastin-65.

Proc Natl Acad Sci U S A 2021 Mar;118(9)

State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, 210032 Nanjing, China;

Long-term potentiation (LTP) has long been considered as an important cellular mechanism for learning and memory. LTP expression involves NMDA receptor-dependent synaptic insertion of AMPA receptors (AMPARs). However, how AMPARs are recruited and anchored at the postsynaptic membrane during LTP remains largely unknown. Read More

View Article and Full-Text PDF

Structure and plasticity of silent synapses in developing hippocampal neurons visualized by super-resolution imaging.

Cell Discov 2020 Feb 25;6(1). Epub 2020 Feb 25.

Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230027, China.

Excitatory synapses in the mammalian brain exhibit diverse functional properties in transmission and plasticity. Directly visualizing the structural correlates of such functional heterogeneity is often hindered by the diffraction-limited resolution of conventional optical imaging techniques. Here, we used super-resolution stochastic optical reconstruction microscopy (STORM) to resolve structurally distinct excitatory synapses formed on dendritic shafts and spines. Read More

View Article and Full-Text PDF
February 2020

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

View Article and Full-Text PDF

Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse.

Elife 2021 Feb 22;10. Epub 2021 Feb 22.

Vollum Institute and Oregon Hearing Research Center, Oregon Health & Science University, Portland, United States.

Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC's large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1-2. Read More

View Article and Full-Text PDF
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

View Article and Full-Text PDF
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

View Article and Full-Text PDF

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

View Article and Full-Text PDF
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

View Article and Full-Text PDF
February 2021

Palmitoylation Controls NMDA Receptor Function and Steroid Sensitivity.

J Neurosci 2021 Mar 1;41(10):2119-2134. Epub 2021 Feb 1.

Institute of Physiology CAS, Prague 4, 142 20, Czech Republic

NMDARs are ligand-gated ion channels that cause an influx of Na and Ca into postsynaptic neurons. The resulting intracellular Ca transient triggers synaptic plasticity. When prolonged, it may induce excitotoxicity, but it may also activate negative feedback to control the activity of NMDARs. Read More

View Article and Full-Text PDF

Further evidence that CP-AMPARs are critically involved in synaptic tag and capture at hippocampal CA1 synapses.

Mol Brain 2021 02 1;14(1):26. Epub 2021 Feb 1.

School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, Korea.

The synaptic tag and capture (STC) hypothesis provides an important theoretical basis for understanding the synaptic basis of associative learning. We recently provided pharmacological evidence that calcium-permeable AMPA receptors (CP-AMPARs) are a crucial component of this form of heterosynaptic metaplasticity. Here we have investigated two predictions that arise on the basis of CP-AMPARs serving as a trigger of STC. Read More

View Article and Full-Text PDF
February 2021

Cocaine-seeking behaviour is differentially expressed in male and female mice exposed to maternal separation and is associated with alterations in AMPA receptors subunits in the medial prefrontal cortex.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Jan 23;109:110262. Epub 2021 Jan 23.

Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain; Neuroscience Research Program, IMIM-Hospital del Mar Research Institute, Barcelona, Spain. Electronic address:

According with clinical data, women evolve differently from drug use to drug abuse. Among drugs of abuse, cocaine is the most consumed psychostimulant. Animal studies demonstrated that females show increased motivation to seek cocaine during the self-administration paradigm (SA) than males. Read More

View Article and Full-Text PDF
January 2021

Biodistribution and radiation dosimetry of the positron emission tomography probe for AMPA receptor, [C]K-2, in healthy human subjects.

Sci Rep 2021 Jan 15;11(1):1598. Epub 2021 Jan 15.

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

[C]K-2, a radiotracer exhibiting high affinity and selectivity for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), is suitable for the quantification of AMPARs in living human brains and potentially useful in the identification of epileptogenic foci in patients. This study aimed to estimate the radiation doses of [C]K-2 in various organs and calculate the effective dose after injection of [C]K-2 in healthy human subjects. Twelve healthy male subjects were registered and divided into two groups (370 or 555 MBq of [C]K-2), followed by 2 h whole-body scans. Read More

View Article and Full-Text PDF
January 2021

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

View Article and Full-Text PDF
January 2021

AMPA and NMDA Receptor Trafficking at Cocaine-Generated Synapses.

J Neurosci 2021 Mar 12;41(9):1996-2011. Epub 2021 Jan 12.

Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260

Cocaine experience generates AMPA receptor (AMPAR)-silent synapses in the nucleus accumbens (NAc), which are thought to be new synaptic contacts enriched in GluN2B-containing NMDA receptors (NMDARs). After drug withdrawal, some of these synapses mature by recruiting AMPARs, strengthening the newly established synaptic transmission. Silent synapse generation and maturation are two consecutive cellular steps through which NAc circuits are profoundly remodeled to promote cue-induced cocaine seeking after drug withdrawal. Read More

View Article and Full-Text PDF

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

View Article and Full-Text PDF
January 2021

Progesterone modulates neuronal excitability bidirectionally.

Neurosci Lett 2021 01 6;744:135619. Epub 2021 Jan 6.

Department of Neurology, University of Virginia-HSC, Charlottesville, VA, 22908, United States. Electronic address:

Progesterone acts on neurons directly by activating its receptor and through metabolic conversion to neurosteroids. There is emerging evidence that progesterone exerts excitatory effects by activating its cognate receptors (progesterone receptors, PRs) through enhanced expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). Progesterone metabolite 5α,3α-tetrahydro-progesterone (allopregnanolone, THP) mediates its anxiolytic and sedative actions through the potentiation of synaptic and extrasynaptic γ-aminobutyric acid type-A receptors (GABARs). Read More

View Article and Full-Text PDF
January 2021

Chronic administration of Tat-GluR23Y ameliorates cognitive dysfunction targeting CREB signaling in rats with amyloid beta neurotoxicity.

Metab Brain Dis 2021 04 9;36(4):701-709. Epub 2021 Jan 9.

Cellular & Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, 8th Km of Rasht -Tehran road, Guilan University Complex, Rasht, Guilan, 41996-13769, Iran.

Alzheimer's disease (AD) is behaviorally characterized by memory impairments, and pathologically by amyloid β1-42 (Aβ1-42) plaques and tangles. Aβ binds to excitatory synapses and disrupts their transmission due to dysregulation of the glutamate receptors. Here we hypothesized that chronic inhibition of the endocytosis of AMPA receptors together with GluN2B subunit of NMDA receptors might improve cognition deficit induced by Aβ(1-42) neurotoxicity. Read More

View Article and Full-Text PDF

Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking.

Sci Rep 2021 Jan 8;11(1):231. Epub 2021 Jan 8.

Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.

Alcohol use disorder exhausts substantial social and economic costs, with recent dramatic increases in female problem drinking. Thus, it is critically important to understand signaling differences underlying alcohol consumption across the sexes. Orexin-1 receptors (Ox1Rs) can strongly promote motivated behavior, and we previously identified Ox1Rs within nucleus accumbens shell (shell) as crucial for driving binge intake in higher-drinking male mice. Read More

View Article and Full-Text PDF
January 2021

Adenosine Signaling and Clathrin-Mediated Endocytosis of Glutamate AMPA Receptors in Delayed Hypoxic Injury in Rat Hippocampus: Role of Casein Kinase 2.

Mol Neurobiol 2021 May 7;58(5):1932-1951. Epub 2021 Jan 7.

Department of Surgery, Neuroscience Research Cluster, College of Medicine, University of Saskatchewan, Room GD30.4, D-Wing Health Science Building, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada.

Chronic adenosine A1R stimulation in hypoxia leads to persistent hippocampal synaptic depression, while unopposed adenosine A2AR receptor stimulation during hypoxia/reperfusion triggers adenosine-induced post-hypoxia synaptic potentiation (APSP) and increased neuronal death. Still, the mechanisms responsible for this adenosine-mediated neuronal damage following hypoxia need to be fully elucidated. We tested the hypothesis that A1R and A2AR regulation by protein kinase casein kinase 2 (CK2) and clathrin-dependent endocytosis of AMPARs both contribute to APSPs and neuronal damage. Read More

View Article and Full-Text PDF

Clmp Regulates AMPA and Kainate Receptor Responses in the Neonatal Hippocampal CA3 and Kainate Seizure Susceptibility in Mice.

Front Synaptic Neurosci 2020 21;12:567075. Epub 2020 Dec 21.

Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, South Korea.

Synaptic adhesion molecules regulate synapse development through trans-synaptic adhesion and assembly of diverse synaptic proteins. Many synaptic adhesion molecules positively regulate synapse development; some, however, exert negative regulation, although such cases are relatively rare. In addition, synaptic adhesion molecules regulate the amplitude of post-synaptic receptor responses, but whether adhesion molecules can regulate the kinetic properties of post-synaptic receptors remains unclear. Read More

View Article and Full-Text PDF
December 2020

PKA-Dependent Membrane Surface Recruitment of CI-AMPARs Is Crucial for BCP-Mediated Protection Against Post-acute Ischemic Stroke Cognitive Impairment.

Front Neurol 2020 16;11:566067. Epub 2020 Dec 16.

Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing, China.

Post-acute ischemic stroke cognitive impairment frequently occurs and seriously affects patients daily activities. Recruitment of GluA2-containing Ca-impermeable AMPA receptors (CI-AMPARs) to hippocampal synaptic membrane surfaces was shown to trigger synaptic plasticity. Currently, the effect of CI-AMPAR trafficking on acute ischemic stroke remains poorly understood. Read More

View Article and Full-Text PDF
December 2020