High actin concentrations in brain dendritic spines and postsynaptic densities.

Matus, Andrew; Ackermann, Marcel; Pehling, Gundula; Byers, H. Randolph; Fujiwara, Keigi

doi:10.1073/pnas.79.23.7590

Cited by 354 publications

(255 citation statements)

References 39 publications

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“…EGFP-actin was localized to dendritic spines (see Fig. 7, which is published as supporting information on the PNAS web site), in close agreement with reports of endogenous actin molecules (29,30). Furthermore, synapses and dendritic spines were formed intact in the presence of EGFP-actin (data not…”

Section: Synaptic Activity Induced Multiple Types Of Actin Reorganizasupporting

confidence: 88%

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Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca ²⁺ channels

Furuyashiki

Arakawa

Takemoto-Kimura

et al. 2002

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

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Cytoskeleton is believed to contribute to activity-dependent processes underlying neuronal plasticity, such as regulations of cellular morphology and localization of signaling proteins. However, how neuronal activity controls actin cytoskeleton remains obscure. Taking E stablishment and remodeling of neural connections require a spatially and temporally orchestrated control of neuronal morphology (1, 2) and fine-tuning of assemblies of signaling complexes (3-8). Although such dynamic reorganization is common during embryonic development, recent evidence indicated that, even in mature brain tissues, neuronal activity may initiate and regulate the active modification of cell shape (9-15) and the sorting of neuronal molecules (16)(17)(18)(19). In vitro studies suggest the requirement for an actin-based mechanism in dendritic spine motility (20, 21) as well as in localization of synaptic proteins at the postsynaptic density (22). These lines of evidence indicate the importance of cytoskeletal signaling in regulating neuronal properties even after their functional maturation.Despite a growing interest in the role of actin remodeling during activity-dependent modification of neuronal properties, the fundamental question as to how neuronal activity regulates actin filaments has not been settled. For instance, neuronal activity has been associated with either an increase (9,11,14,15) or a decrease (10, 13) in the number of dendritic spines. Furthermore, intracellular Ca 2ϩ rise seemed to give rise to opposite effects on actin cytoskeleton. Ca 2ϩ -dependent accumulation of actin has been reported in goldfish retinal bipolar cells (23) and in developing grasshopper neurons (24), whereas others have found an N-methyl-D-aspartate (NMDA)-stimulated actin dislocation at dendritic spines (25,26). These apparently conflicting observations raise the possibility that activity-dependent regulation of actin reorganization may be ruled by multiple coexisting modes of signaling from synapse to cytoskeleton.Setting aside such controversy, most studies have similarly argued that intracellular Ca 2ϩ is involved in actin reorganization (23-27). Recent pharmacological evidence has highlighted the diversity of Ca 2ϩ entry sources, each of which may have distinct functions in various cellular phenomena, such as synaptic plasticity (for review, see ref. 4) and gene expression (28). Previous work on Ca 2ϩ -induced actin responses indeed used various kinds of stimulation protocols which were likely to activate distinct routes of Ca 2ϩ entry. Thus, the reported dichotomy in Ca 2ϩ -mediated actin responses might reflect the functional segregation of different Ca 2ϩ sources, each contributing distinctly during actin reorganization. To gain definitive insights into these issues, we visualized directly actin dynamics in live, synaptically connected, cultured hippocampal neurons by use of enhanced GFP (EGFP)-actin and analyzed Ca 2ϩ -based mechanisms in activitydependent actin reorganization. Materials and MethodsConstruction of the adenovirus whic...

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Section: Synaptic Activity Induced Multiple Types Of Actin Reorganizasupporting

confidence: 88%

“…Actin filaments are major components of the cytoskeleton at the postsynaptic sites of the excitatory synapses (29,30). The bivalent nature of actin cytoskeleton dynamics, rigidity, and plasticity has attracted neurobiologists for decades as a possible molecular basis that may account for certain kinds of synaptic plasticity (30).…”

Section: Discussionmentioning

confidence: 99%

Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca ²⁺ channels

Furuyashiki

Arakawa

Takemoto-Kimura

et al. 2002

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

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“…Indeed, the morphogenesis of dendritic spines, which are the main site of innervation by excitatory glutamatergic presynaptic terminals, plays an important role in synaptic plasticity (Fukazawa et al, 2003;Matsuzaki et al, 2004;Nagerl et al, 2004;Okamoto et al, 2004;Zhou et al, 2004). A remarkable feature of the cytoskeleton of dendritic spines is its enriched level of filamentous actin (F-actin) (Fifkova and Morales, 1992;Matus et al, 1982). The mechanisms that regulate F-actin dynamics in the spine contribute to the induction, extent and maintenance of hippocampal LTP Long-lasting modifications in synaptic transmission depend on de novo gene expression in neurons.…”

Section: Introductionmentioning

confidence: 99%

Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics

Shoji-Kasai

Ageta

Hasegawa

et al. 2007

Journal of Cell Science

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Long-lasting modifications in synaptic transmission depend on de novo gene expression in neurons. The expression of activin, a member of the transforming growth factor β (TGF-β) superfamily, is upregulated during hippocampal long-term potentiation (LTP). Here, we show that activin increased the average number of presynaptic contacts on dendritic spines by increasing the population of spines that were contacted by multiple presynaptic terminals in cultured neurons. Activin also induced spine lengthening, primarily by elongating the neck, resulting in longer mushroom-shaped spines. The number of spines and spine head size were not significantly affected by activin treatment. The effects of activin on spinal filamentous actin (F-actin) morphology were independent of protein and RNA synthesis. Inhibition of cytoskeletal actin dynamics or of the mitogen-activated protein (MAP) kinase pathway blocked not only the activin-induced increase in the number of terminals contacting a spine but also the activin-induced lengthening of spines. These results strongly suggest that activin increases the number of synaptic contacts by modulating actin dynamics in spines, a process that might contribute to the establishment of late-phase LTP.

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“…In hippocampal area CA1, naturalistic patterns of theta-stimulation readily induce long-term potentiation (LTP) of the excitatory, glutamatergic Schaffer collateral afferent inputs that target dendritic spines (1), which are small, actin-rich dendritic protrusions that harbor the majority of the excitatory synapses (2). Studies show that dendritic spines undergo significant morphological remodeling in association with long-lasting plasticity (3).…”

mentioning

confidence: 99%

Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately

Wang

Bozdagi

Nikitczuk

et al. 2008

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

293

323

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Persistent dendritic spine enlargement is associated with stable long-term potentiation (LTP), and the latter is thought to underlie long-lasting memories. Extracellular proteolytic remodeling of the synaptic microenvironment could be important for such plasticity, but whether or how proteolytic remodeling contributes to persistent modifications in synapse structure and function is unknown. Matrix metalloproteinase-9 (MMP-9) is an extracellular protease that is activated perisynaptically after LTP induction and required for LTP maintenance. Here, by monitoring spine size and excitatory postsynaptic potentials (EPSPs) simultaneously with combined 2-photon time-lapse imaging and whole-cell recordings from hippocampal neurons, we find that MMP-9 is both necessary and sufficient to drive spine enlargement and synaptic potentiation concomitantly. Both structural and functional MMP-driven forms of plasticity are mediated through ␤1-containing integrin receptors, are associated with integrin-dependent cofilin inactivation within spines, and require actin polymerization. In contrast, postsynaptic exocytosis and protein synthesis are both required for MMP-9-induced potentiation, but not for initial MMP-9-induced spine expansion. However, spine expansion becomes unstable when postsynaptic exocytosis or protein synthesis is blocked, indicating that the 2 forms of plasticity are expressed independently but require interactions between them for persistence. When MMP activity is eliminated during theta-stimulation-induced LTP, both spine enlargement and synaptic potentiation are transient. Thus, MMP-mediated extracellular remodeling during LTP has an instructive role in establishing persistent modifications in both synapse structure and function of the kind critical for learning and memory.actin ͉ cofilin ͉ integrin ͉ synaptic plasticity ͉ protein synthesis L ong-lasting memory is based on long-term modifications of synapse structure and function. In hippocampal area CA1, naturalistic patterns of theta-stimulation readily induce long-term potentiation (LTP) of the excitatory, glutamatergic Schaffer collateral afferent inputs that target dendritic spines (1), which are small, actin-rich dendritic protrusions that harbor the majority of the excitatory synapses (2). Studies show that dendritic spines undergo significant morphological remodeling in association with long-lasting plasticity (3). Spine growth, for example, is associated with the induction of LTP and is thought to be important for supporting persistent changes in synaptic strength (4-6). However, little is known about signals that instruct and coordinate persistent modifications in synapse structure and function during LTP.Dendritic spine morphology and synaptic potentiation can both be dynamically modulated by proteins of the extracellular matrix (ECM) and the cell-surface proteins with which they interact, which has long fueled the idea that regulated ECM remodeling has an important role in synaptic plasticity (7). How precisely such remodeling could occur is not u...

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High actin concentrations in brain dendritic spines and postsynaptic densities.

Cited by 354 publications

References 39 publications

Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca ²⁺ channels

Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca ²⁺ channels

Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics

Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately

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High actin concentrations in brain dendritic spines and postsynaptic densities.

Cited by 354 publications

References 39 publications

Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca 2+ channels

Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca 2+ channels

Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics

Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately

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Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca ²⁺ channels

Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca ²⁺ channels