Long-Term Potentiation-Dependent Spine Enlargement Requires Synaptic Ca<sup>2+</sup>-Permeable AMPA Receptors Recruited by CaM-Kinase I

Fortin, Dale A.; Davare, Monika A.; Srivastava, Taasin; Brady, James D.; Nygaard, Sean; Derkach, V. A.; Soderling, Thomas R.

doi:10.1523/jneurosci.1746-10.2010

Cited by 169 publications

(171 citation statements)

References 82 publications

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“…GluR2-lacking AMPA receptors are Ca 2ϩ -permeable, whereas GluR2-containing AMPA receptors are not (Liu and Zukin, 2007 . Given the various roles of CP-AMPA receptors in synaptic plasticity (Liu and Zukin, 2007;Fortin et al, 2010), it is possible that morphine may affect intracellular Ca 2ϩ levels via modulation of AMPA receptor calcium permeability. Although data in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The GFP and DsRed constructs (Clontech) were also expressed in the pRK5 vector and driven by a CMV promoter. Concentrations used were 10 M morphine, 10 M naloxone, 10 (Tokumitsu et al, 1990), 1 M tacrolimus (FK506) (Lieberman and Mody, 1994;Kam et al, 2010), and 30 M N,N,N,-trimethyl-5-[(tricyclo]3.3.1.13,7[dec-1-ylmethyl) amino]-1-pentanaminiumbromide hydrobromide (IEM-1460) (Fortin et al, 2010). Drugs were added to the culture media at 21 DIV and remained for the length of the experiments.…”

Section: High-density Neuronal Cultures and Neuronal Transfectionmentioning

confidence: 99%

“…Although it is not clear how morphine causes changes in intracellular Ca 2ϩ , it is probably not due to an influx through N-methyl- molpharm.aspetjournals.org D-aspartate channels . The presence of Ca 2ϩ -permeable (CP) AMPA glutamate receptors (GluR2-lacking) at synapses has been shown to be highly plastic (Liu and Zukin, 2007;Fortin et al, 2010). CP-AMPA receptors could play a role in the effects of morphine on spine density.…”

Section: Inhibition Of Both Camkii and Calcineurin Preventsmentioning

confidence: 99%

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Differential Modulation of Drug-Induced Structural and Functional Plasticity of Dendritic Spines

Miller¹,

Zhang²,

Dummer³

et al. 2012

Mol Pharmacol

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Drug-induced plasticity of excitatory synapses has been proposed to be the cellular mechanism underlying the aberrant learning associated with addiction. Exposure to various drugs of abuse causes both morphological plasticity of dendritic spines and functional plasticity of excitatory synaptic transmission. Chronic activation of -opioid receptors (MOR) in cultured hippocampal neurons causes two forms of synaptic plasticity: loss of dendritic spines and loss of synaptic ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. With use of live imaging, patch-clamp electrophysiology, and immunocytochemistry, the present study reveals that these two forms of synaptic plasticity are mediated by separate, but interactive, intracellular signaling cascades. The inhibition of Ca 2ϩ /calmodulin-dependent protein kinase II with 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) blocks MOR-mediated structural plasticity of dendritic spines, but not MOR-mediated cellular redistribution of GluR1 and GluR2 AMPA receptor subunits. In contrast, the inhibition of calcineurin with tacrolimus (FK506) blocks both cellular processes. These findings support the idea that drug-induced structural and functional plasticity of dendritic spines is mediated by divergent, but interactive, signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Section: High-density Neuronal Cultures and Neuronal Transfectionmentioning

confidence: 99%

Section: Inhibition Of Both Camkii and Calcineurin Preventsmentioning

confidence: 99%

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Differential Modulation of Drug-Induced Structural and Functional Plasticity of Dendritic Spines

Miller¹,

Zhang²,

Dummer³

et al. 2012

Mol Pharmacol

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“…Spines have been reported to incorporate AMPA receptors early in their development (13,27,28). Apart from additional roles in long-lasting synapses, AMPA receptor activity has been associated with the stabilization of immature spines, possibly, at least in part, via actin-dependent pathways (4,14,(29)(30)(31)(32)(33)(34)(35).In neurons, the O-GlcNAc pathway has emerged recently as critical for coupling cellular function to energy availability through nutrient-dependent flux via the hexosamine biosynthesis pathway (HBP), of which the OGT donor substrate uridine diphosphate (UDP)-GlcNAc is the end product (36-40). Unlike complex glycans present on the outside of cells and in the secretory pathway, O-GlcNAc is a highly dynamic sugar that is added and removed repeatedly over the lifespan of a single peptide chain.…”

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confidence: 99%

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O-GlcNAc transferase regulates excitatory synapse maturity

Lagerlöf

Hart

Huganir

2017

Proc. Natl. Acad. Sci. U.S.A.

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Experience-driven synaptic plasticity is believed to underlie adaptive behavior by rearranging the way neuronal circuits process information. We have previously discovered that O-GlcNAc transferase (OGT), an enzyme that modifies protein function by attaching β-N-acetylglucosamine (GlcNAc) to serine and threonine residues of intracellular proteins (O-GlcNAc), regulates food intake by modulating excitatory synaptic function in neurons in the hypothalamus. However, how OGT regulates excitatory synapse function is largely unknown. Here we demonstrate that OGT is enriched in the postsynaptic density of excitatory synapses. In the postsynaptic density, O-GlcNAcylation on multiple proteins increased upon neuronal stimulation. Knockout of the OGT gene decreased the synaptic expression of the AMPA receptor GluA2 and GluA3 subunits, but not the GluA1 subunit. The number of opposed excitatory presynaptic terminals was sharply reduced upon postsynaptic knockout of OGT. There were also fewer and less mature dendritic spines on OGT knockout neurons. These data identify OGT as a molecular mechanism that regulates synapse maturity.O-GlcNAc | OGT | excitatory synapses | AMPA receptors N euronal synapses, the cell-cell junctions over which neurons communicate, are formed and eliminated throughout life, and their turnover has for decades been associated with the way neuronal circuits adapt to environmental challenges to optimize behavior (1, 2). In both humans and animals, early development is characterized by massive generation of new synapses. About half of all synapses are then lost during adolescence (2, 3). Most mature excitatory synapses occur on dendritic protrusions called spines and essentially all spines contain an excitatory synapse (4-6). In vivo imaging of individual spines for days to months has shown that adult spines are largely stable but a small subpopulation remains plastic (3, 7) and spine turnover is increased by novel experience (5,(8)(9)(10). Whereas most new spines are thin and withdraw rapidly, some enlarge and form stable synaptic contacts (2,3,7,(11)(12)(13)(14). In fact, the stabilization of a subset of new spines correlates with behavioral performance in several different tasks in multiple animal species (13,(15)(16)(17). Rather than synapse formation or density, the selection of which spines are retained once formed has been suggested to match circuit architecture with behavior (18). Without affecting spine formation, deleting β-adducin, which regulates actin, perturbed the process by which nascent spines establish functional synapses and impaired long-term memory (19). Fragile X syndrome, a common form of mental retardation, exhibits a higher than normal density of spines but more of them exhibit an immature morphology and their turnover is not affected by sensory experience (9,20). Conversely, the protein Telencephalin arrests the maturation of spines and its removal enhances several forms of learning (13,21,22).Although many molecules have been identified that affect synapse number, it is unclear h...

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The Ca²⁺ and Rho GTPase signaling pathways underlying activity‐dependent actin remodeling at dendritic spines

Saneyoshi

Hayashi

2012

Cytoskeleton

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Most excitatory synapses reside on small protrusions located on the dendritic shaft of neurons called dendritic spines. Neuronal activity regulates the number and structure of spines in both developing and mature brains. Such morphological changes are mediated by the modification of the actin cytoskeleton, the major structural component of spines. Because the number and size of spines is tightly correlated with the strength of synaptic transmission, the activity-dependent structural remodeling of a spine plays an important role in the modulation of synaptic transmission. The regulation of spine morphogenesis utilizes multiple intracellular signaling pathways that alter the dynamics of actin remodeling. Here, we will review recent studies examining the signaling pathways underlying activitydependent actin remodeling at excitatory postsynaptic neurons. V C 2012 Wiley Periodicals, Inc

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Long-Term Potentiation-Dependent Spine Enlargement Requires Synaptic Ca²⁺-Permeable AMPA Receptors Recruited by CaM-Kinase I

Abstract: It is well established that long-term potentiation (LTP),

Cited by 169 publications

References 82 publications

Differential Modulation of Drug-Induced Structural and Functional Plasticity of Dendritic Spines

Differential Modulation of Drug-Induced Structural and Functional Plasticity of Dendritic Spines

O-GlcNAc transferase regulates excitatory synapse maturity

The Ca²⁺ and Rho GTPase signaling pathways underlying activity‐dependent actin remodeling at dendritic spines

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Long-Term Potentiation-Dependent Spine Enlargement Requires Synaptic Ca2+-Permeable AMPA Receptors Recruited by CaM-Kinase I

Abstract: It is well established that long-term potentiation (LTP),

Cited by 169 publications

References 82 publications

Differential Modulation of Drug-Induced Structural and Functional Plasticity of Dendritic Spines

Differential Modulation of Drug-Induced Structural and Functional Plasticity of Dendritic Spines

O-GlcNAc transferase regulates excitatory synapse maturity

The Ca2+ and Rho GTPase signaling pathways underlying activity‐dependent actin remodeling at dendritic spines

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Product

Resources

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Long-Term Potentiation-Dependent Spine Enlargement Requires Synaptic Ca²⁺-Permeable AMPA Receptors Recruited by CaM-Kinase I

The Ca²⁺ and Rho GTPase signaling pathways underlying activity‐dependent actin remodeling at dendritic spines