131 results match your criteria post-synaptic camkii

The role of CaMKII autophosphorylation for NMDA receptor-dependent synaptic potentiation.

Karl Peter Giese

Neuropharmacology 2021 May 26;193:108616. Epub 2021 May 26.

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Building, King's College London, 5 Cutcombe Road, London, SE5 9NU, UK. Electronic address:

Potentiation of glutamatergic synaptic transmission is thought to underlie memory. The induction of this synaptic potentiation relies on activation of NMDA receptors which allows for calcium influx into the post-synapse. A key mechanistic question for the understanding of synaptic potentiation is what signaling is activated by the calcium influx. Read More

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Role of Fto on CaMKII/CREB signaling pathway of hippocampus in depressive-like behaviors induced by chronic restraint stress mice.

Behav Brain Res 2021 May 5;406:113227. Epub 2021 Mar 5.

Department of Neurology, Huadong Hospital, Fudan University, 221 West Yan An Road, Shanghai, 200040, China. Electronic address:

Background: Major depressive disorders (MDD) is one of the most common mental illness in the world. Recently, brain mA /m (fat mass- and obesity-associated gene Fto) was found that exerted an important role in regulating gene expression involved in stress related depression. However, the potential mechanism of Fto on depression still remains elusive. Read More

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Coordination between Calcium/Calmodulin-Dependent Protein Kinase II and Neuronal Nitric Oxide Synthase in Neurons.

Int J Mol Sci 2020 Oct 27;21(21). Epub 2020 Oct 27.

Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.

Ca/calmodulin (CaM)-dependent protein kinase II (CaMKII) is highly abundant in the brain and exhibits broad substrate specificity, thereby it is thought to participate in the regulation of neuronal death and survival. Nitric oxide (NO), produced by neuronal NO synthase (nNOS), is an important neurotransmitter and plays a role in neuronal activity including learning and memory processes. However, high levels of NO can contribute to excitotoxicity following a stroke and neurodegenerative disease. Read More

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October 2020

A unified computational model for cortical post-synaptic plasticity.

Elife 2020 07 30;9. Epub 2020 Jul 30.

The Krasnow Institute for Advanced Study, George Mason University, Fairfax, United States.

Signalling pathways leading to post-synaptic plasticity have been examined in many types of experimental studies, but a unified picture on how multiple biochemical pathways collectively shape neocortical plasticity is missing. We built a biochemically detailed model of post-synaptic plasticity describing CaMKII, PKA, and PKC pathways and their contribution to synaptic potentiation or depression. We developed a statistical AMPA-receptor-tetramer model, which permits the estimation of the AMPA-receptor-mediated maximal synaptic conductance based on numbers of GluR1s and GluR2s predicted by the biochemical signalling model. Read More

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Signaling models for dopamine-dependent temporal contiguity in striatal synaptic plasticity.

PLoS Comput Biol 2020 07 23;16(7):e1008078. Epub 2020 Jul 23.

Integrated Systems Biology Laboratory, Department of Systems Science, Graduate School of Informatics, Kyoto University, Sakyo-ku, Kyoto, Japan.

Animals remember temporal links between their actions and subsequent rewards. We previously discovered a synaptic mechanism underlying such reward learning in D1 receptor (D1R)-expressing spiny projection neurons (D1 SPN) of the striatum. Dopamine (DA) bursts promote dendritic spine enlargement in a time window of only a few seconds after paired pre- and post-synaptic spiking (pre-post pairing), which is termed as reinforcement plasticity (RP). Read More

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Interactions between calmodulin and neurogranin govern the dynamics of CaMKII as a leaky integrator.

PLoS Comput Biol 2020 07 17;16(7):e1008015. Epub 2020 Jul 17.

Institute for Neural Computation, University of California San Diego, La Jolla, California, United States of America.

Calmodulin-dependent kinase II (CaMKII) has long been known to play an important role in learning and memory as well as long term potentiation (LTP). More recently it has been suggested that it might be involved in the time averaging of synaptic signals, which can then lead to the high precision of information stored at a single synapse. However, the role of the scaffolding molecule, neurogranin (Ng), in governing the dynamics of CaMKII is not yet fully understood. Read More

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Activity-dependent redistribution of CaMKII in the postsynaptic compartment of hippocampal neurons.

Mol Brain 2020 04 1;13(1):53. Epub 2020 Apr 1.

NINDS Electron Microscopy Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA.

Calcium/calmodulin-dependent protein kinase II (CaMKII), an abundant protein in neurons, is involved in synaptic plasticity and learning. CaMKII associates with multiple proteins located at or near the postsynaptic density (PSD), and CaMKII is known to translocate from cytoplasm to PSD under excitatory conditions. The present study examined the laminar distribution of CaMKII at the PSD by immunogold labeling in dissociated hippocampal cultures under low calcium (EGTA or APV), control, and stimulated (depolarization with high K or NMDA) conditions. Read More

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PSD-95 Serine 73 phosphorylation is not required for induction of NMDA-LTD.

Sci Rep 2020 02 6;10(1):2054. Epub 2020 Feb 6.

Laboratory of Molecular Basis of Behavior, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.

PSD-95 is a major scaffolding protein of the post-synaptic density (PSD) of a glutamatergic synapse. PSD-95, via interactions with stargazin, anchors AMPA receptors at the synapse and regulates AMPAR currents. The expression of PSD-95 is regulated during synaptic plasticity. Read More

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February 2020

A Cellular Mechanism of Learning-Induced Enhancement of Synaptic Inhibition: PKC-Dependent Upregulation of KCC2 Activation.

Sci Rep 2020 01 22;10(1):962. Epub 2020 Jan 22.

Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel.

Long-term memory of complex olfactory learning is expressed by wide spread enhancement in excitatory and inhibitory synaptic transmission onto piriform cortex pyramidal neurons. A particularly interesting modification in synaptic inhibition is the hyperpolarization of the reversal potential of the fast post synaptic inhibitory potential (fIPSP). Here we study the mechanism underlying the maintenance of such a shift in the fIPSP. Read More

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January 2020

SK Channel Modulates Synaptic Plasticity by Tuning CaMKIIα/β Dynamics.

Front Synaptic Neurosci 2019 31;11:18. Epub 2019 Oct 31.

Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, United States.

N-Methyl-D-Aspartate Receptor 1 (NMDAR)-linked Ca current represents a significant percentage of post-synaptic transient that modulates synaptic strength and is pertinent to dendritic spine plasticity. In the hippocampus, Ca transient produced by glutamatergic ionotropic neurotransmission facilitates Ca-Calmodulin-dependent kinase 2 (CaMKII) Thr286 phosphorylation and promote long-term potentiation (LTP) expression. At CA1 post-synaptic densities, Ca transients equally activate small conductance (SK2) channel which regulates excitability by suppressing Ca movement. Read More

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October 2019

The 5-HT1A receptor: Signaling to behavior.

Biochimie 2019 Jun 25;161:34-45. Epub 2018 Oct 25.

Ottawa Hospital Research Institute (Neuroscience), UOttawa Brain and Mind Research Institute, Ottawa, ON, K1H-8M5, Canada.

The 5-HT1A receptor is highly expressed both in 5-HT neurons as a presynaptic inhibitory autoreceptor, and in many brain regions innervated by 5-HT as a post-synaptic heteroreceptor. This review examines the signaling of 5-HT1A receptors to regulate 5-HT activity and behavior. Initial findings in heterologous cell systems, neuronal cell lines, neurons, and in vivo show that the 5-HT1A receptor is a Gi/o-coupled receptor that signals to the canonical pathway of inhibition of adenylyl cyclase (AC). Read More

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CAMK2-Dependent Signaling in Neurons Is Essential for Survival.

J Neurosci 2019 07 7;39(28):5424-5439. Epub 2019 May 7.

Department of Neuroscience,

Ca/calmodulin-dependent protein kinase II (CAMK2) is a key player in synaptic plasticity and memory formation. Mutations in or cause intellectual disability in humans, and severe plasticity and learning deficits in mice, indicating unique functions for each isoform. However, considering the high homology between CAMK2A and CAMK2B, it is conceivable that for critical functions, one isoform compensates for the absence of the other, and that the full functional spectrum of neuronal CAMK2 remains to be revealed. Read More

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Early Life Sleep Deprivation: Role of Oxido-Inflammatory Processes.

Neuroscience 2019 May 1;406:22-37. Epub 2019 Mar 1.

University of Houston, Houston, TX. Electronic address:

The adverse consequences of early-life sleep deprivation on mental health are well recognized, yet many aspects remain unknown, therefore, animal studies can offer useful insights. Male Sprague-Dawley rats at postnatal day (PND) 19 were subjected to sleep deprivation (SD) for 14 days (6-8 hours/day). Control (CON) rats were gently handled. Read More

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Subunit exchange enhances information retention by CaMKII in dendritic spines.

Elife 2018 11 12;7. Epub 2018 Nov 12.

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.

Molecular bistables are strong candidates for long-term information storage, for example, in synaptic plasticity. Calcium/calmodulin-dependent protein Kinase II (CaMKII) is a highly expressed synaptic protein which has been proposed to form a molecular bistable switch capable of maintaining its state for years despite protein turnover and stochastic noise. It has recently been shown that CaMKII holoenzymes exchange subunits among themselves. Read More

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November 2018

Distribution of densin in neurons.

PLoS One 2018 16;13(10):e0205859. Epub 2018 Oct 16.

Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.

Densin is a scaffold protein known to associate with key elements of neuronal signaling. The present study examines the distribution of densin at the ultrastructural level in order to reveal potential sites that can support specific interactions of densin. Immunogold electron microscopy on hippocampal cultures shows intense labeling for densin at postsynaptic densities (PSDs), but also some labeling at extrasynaptic plasma membranes of soma and dendrites and endoplasmic reticulum. Read More

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CaMKIIβ is localized in dendritic spines as both drebrin-dependent and drebrin-independent pools.

J Neurochem 2018 07 11;146(2):145-159. Epub 2018 Jun 11.

Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

Drebrin is a major F-actin binding protein in dendritic spines that is critically involved in the regulation of dendritic spine morphogenesis, pathology, and plasticity. In this study, we aimed to identify a novel drebrin-binding protein involved in spine morphogenesis and synaptic plasticity. We confirmed the beta subunit of Ca /calmodulin-dependent protein kinase II (CaMKIIβ) as a drebrin-binding protein using a yeast two-hybrid system, and investigated the drebrin-CaMKIIβ relationship in dendritic spines using rat hippocampal neurons. Read More

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Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation.

Elife 2018 04 5;7. Epub 2018 Apr 5.

Neuroscience Graduate Program, University of Southern California, California, United States.

Postsynaptic compartments can be specifically modulated during various forms of synaptic plasticity, but it is unclear whether this precision is shared at presynaptic terminals. Presynaptic homeostatic plasticity (PHP) stabilizes neurotransmission at the neuromuscular junction, where a retrograde enhancement of presynaptic neurotransmitter release compensates for diminished postsynaptic receptor functionality. To test the specificity of PHP induction and expression, we have developed a genetic manipulation to reduce postsynaptic receptor expression at one of the two muscles innervated by a single motor neuron. Read More

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Striatal Tyrosine Hydroxylase Is Stimulated via TAAR1 by 3-Iodothyronamine, But Not by Tyramine or β-Phenylethylamine.

Front Pharmacol 2018 1;9:166. Epub 2018 Mar 1.

Section of Translational Neuropharmacology, Department of Clinical Neuroscience, Center for Molecular Medicine L8:01, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.

The trace amine-associated receptor 1 (TAAR1) is expressed by dopaminergic neurons, but the precise influence of trace amines upon their functional activity remains to be fully characterized. Here, we examined the regulation of tyrosine hydroxylase (TH) by tyramine and beta-phenylethylamine (β-PEA) compared to 3-iodothyronamine (TAM). Immunoblotting and amperometry were performed in dorsal striatal slices from wild-type (WT) and TAAR1 knockout (KO) mice. Read More

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Altered Intracellular Calcium Homeostasis Underlying Enhanced Glutamatergic Transmission in Striatal-Enriched Tyrosine Phosphatase (STEP) Knockout Mice.

Mol Neurobiol 2018 Oct 5;55(10):8084-8102. Epub 2018 Mar 5.

Department of Experimental Medicine, University of Genova, Viale Benedetto XV 3, 16132, Genoa, Italy.

The striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase involved in synaptic transmission. The current hypothesis on STEP function holds that it opposes synaptic strengthening by dephosphorylating and inactivating key neuronal proteins involved in synaptic plasticity and intracellular signaling, such as the MAP kinases ERK1/2 and p38, as well as the tyrosine kinase Fyn. Although STEP has a predominant role at the post-synaptic level, it is also expressed in nerve terminals. Read More

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October 2018

Activation State-Dependent Substrate Gating in Ca/Calmodulin-Dependent Protein Kinase II.

Neural Plast 2017 17;2017:9601046. Epub 2017 Dec 17.

Biochemistry and Molecular Biology, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Calcium/calmodulin-dependent protein kinase II (CaMKII) is highly concentrated in the brain where its activation by the Ca sensor CaM, multivalent structure, and complex autoregulatory features make it an ideal translator of Ca signals created by different patterns of neuronal activity. We provide direct evidence that graded levels of kinase activity and extent of T (T isoform) autophosphorylation drive changes in catalytic output and substrate selectivity. The catalytic domains of CaMKII phosphorylate purified PSDs much more effectively when tethered together in the holoenzyme versus individual subunits. Read More

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September 2018

LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated with deficits in stimulus processing during Pavlovian conditioning.

J Neuroimmunol 2017 12 28;313:1-9. Epub 2017 Sep 28.

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. Electronic address:

The N-Methyl-d-Aspartate receptor (NMDAR) antagonist kynurenic acid (KYNA) and the post-synaptic calmodulin binding protein neurogranin (Nrgn) have been implicated in neurological and neuropsychiatric conditions including Alzheimer's disease and schizophrenia. This study indicates that systemic dual-lipopolysaccharide (LPS) injections increases KYNA in the medial prefrontal cortex (mPFC), which is accompanied with increased phosphorylation of nuclear factor kappa chain of activated B cells (NFκB) and activation of the nuclear factor of activated T- cells (NFAT). Our results also indicate that dual-LPS increases Nrgn phosphorylation and concomitantly reduces phosphorylation of calmodulin kinase-II (CaMKII). Read More

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December 2017

Nhe5 deficiency enhances learning and memory via upregulating Bdnf/TrkB signaling in mice.

Am J Med Genet B Neuropsychiatr Genet 2017 Dec 5;174(8):828-838. Epub 2017 Oct 5.

State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.

Nhe5, a Na /H exchanger, is predominantly expressed in brain tissue and is proposed to act as a negative regulator of dendritic spine growth. Up to now, its physiological function in vivo remains unclear. Here we show that Nhe5-deficient mice exhibit markedly enhanced learning and memory in Morris water maze, novel object recognition, and passive avoidance task. Read More

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December 2017

Ketamine Self-Administration Elevates αCaMKII Autophosphorylation in Mood and Reward-Related Brain Regions in Rats.

Mol Neurobiol 2018 Jul 25;55(7):5453-5461. Epub 2017 Sep 25.

Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.

Modulation of αCaMKII expression and phosphorylation is a feature shared by drugs of abuse with different mechanisms of action. Accordingly, we investigated whether αCaMKII expression and activation could be altered by self-administration of ketamine, a non-competitive antagonist of the NMDA glutamate receptor, with antidepressant and psychotomimetic as well as reinforcing properties. Rats self-administered ketamine at a sub-anesthetic dose for 43 days and were sacrificed 24 h after the last drug exposure; reward-related brain regions, such as medial prefrontal cortex (PFC), ventral striatum (vS), and hippocampus (Hip), were used for the measurement of αCaMKII-mediated signaling. Read More

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Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIα expression in neural changes associated with a prolonged exposure therapy.

Neuroscience 2017 06 27;353:147-165. Epub 2017 Apr 27.

Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, United States. Electronic address:

Traumatic stress patients showed significant improvement in behavior after a prolonged exposure to an unrelated stimulus. This treatment method attempts to promote extinction of the fear memory associated with the initial traumatic experience. However, the subsequent prolonged exposure to such stimulus creates an additional layer of neural stress. Read More

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Sensitizing exposure to amphetamine increases AMPA receptor phosphorylation without increasing cell surface expression in the rat nucleus accumbens.

Neuropharmacology 2017 05 20;117:328-337. Epub 2017 Feb 20.

Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL 60637, United States. Electronic address:

Exposure to psychostimulants like cocaine or amphetamine leads to long-lasting sensitization of their behavioral and neurochemical effects. Here we characterized changes in AMPA receptor distribution and phosphorylation state in the rat nucleus accumbens (NAcc) weeks after amphetamine exposure to assess their potential contribution to sensitization by this drug. Using protein cross-linking, biochemical, subcellular fractionation, and slice electrophysiological approaches in the NAcc, we found that, unlike cocaine, previous exposure to amphetamine did not increase cell surface levels of either GluA1 or GluA2 AMPA receptor subunits, redistribution of these subunits to the synaptic or perisynaptic cellular membrane domains, protein-protein associations required to support the accumulation and retention of AMPA receptors in the PSD, or the peak amplitude of AMPA receptor mediated mEPSCs recorded in NAcc slices. Read More

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Optogenetic Control of Synaptic Composition and Function.

Neuron 2017 Feb 26;93(3):646-660.e5. Epub 2017 Jan 26.

Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address:

The molecular composition of the postsynaptic membrane is sculpted by synaptic activity. During synaptic plasticity at excitatory synapses, numerous structural, signaling, and receptor molecules concentrate at the postsynaptic density (PSD) to regulate synaptic strength. We developed an approach that uses light to tune the abundance of specific molecules in the PSD. Read More

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February 2017

Neural plasticity and behavior - sixty years of conceptual advances.

J David Sweatt

J Neurochem 2016 10 10;139 Suppl 2:179-199. Epub 2016 Mar 10.

Department of Neurobiology, Evelyn F. McKnight Brain Institute and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.

This brief review summarizes 60 years of conceptual advances that have demonstrated a role for active changes in neuronal connectivity as a controller of behavior and behavioral change. Seminal studies in the first phase of the six-decade span of this review firmly established the cellular basis of behavior - a concept that we take for granted now, but which was an open question at the time. Hebbian plasticity, including long-term potentiation and long-term depression, was then discovered as being important for local circuit refinement in the context of memory formation and behavioral change and stabilization in the mammalian central nervous system. Read More

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October 2016

A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density.

Elife 2016 09 13;5. Epub 2016 Sep 13.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.

SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. Read More

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September 2016

Autocrine BDNF-TrkB signalling within a single dendritic spine.

Nature 2016 Oct 28;538(7623):99-103. Epub 2016 Sep 28.

Neurobiology Department, Duke University Medical Center, Research Drive, Durham, North Carolina 27710, USA.

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are crucial for many forms of neuronal plasticity, including structural long-term potentiation (sLTP), which is a correlate of an animal's learning. However, it is unknown whether BDNF release and TrkB activation occur during sLTP, and if so, when and where. Here, using a fluorescence resonance energy transfer-based sensor for TrkB and two-photon fluorescence lifetime imaging microscopy, we monitor TrkB activity in single dendritic spines of CA1 pyramidal neurons in cultured murine hippocampal slices. Read More

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October 2016

Postsynaptic SDC2 induces transsynaptic signaling via FGF22 for bidirectional synaptic formation.

Sci Rep 2016 09 15;6:33592. Epub 2016 Sep 15.

Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.

Functional synapse formation requires tight coordination between pre- and post-synaptic termini. Previous studies have shown that postsynaptic expression of heparan sulfate proteoglycan syndecan-2 (SDC2) induces dendritic spinogenesis. Those SDC2-induced dendritic spines are frequently associated with presynaptic termini. Read More

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September 2016