Spatial segregation of neuronal calcium signals encodes different forms of LTP in rat hippocampus

Raymond, Clarke R.; Redman, S. J.

doi:10.1113/jphysiol.2005.098947

Cited by 134 publications

(158 citation statements)

References 59 publications

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“…RGD-induced increases in [Ca 2+ ]i appeared first in dendrites and tens of seconds later in somata. This is consistent with integrin ligation first elevating calcium influx and release from local (spine/dendritic) SER stores (Rose and Konnerth, 2001;Raymond and Redman, 2006) followed by a summation of local effects to elicit a second wave of calcium-induced calcium release from the larger SER network, including that in the perikaryon.…”

Section: Discussionsupporting

confidence: 75%

“…These include AMPA receptor trafficking (Maher et al, 2005), local protein synthesis (Dong et al, 2003;Smart et al, 2003;Kelleher et al, 2004) and regulation of calciumactivated proteases Lynch et al, 2007). Moreover, recent work suggests that calcium transients from different sources (i.e., NMDAR-, RyR-, IP3R-mediated) support different epochs in the consolidation of LTP (Rose and Konnerth, 2001;Raymond and Redman, 2006). It remains for future studies to test the hypothesis that these events can be manipulated in a predictable manner by treatments that affect integrin signaling.…”

Section: Discussionmentioning

confidence: 99%

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Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores

Lin

Hilgenberg

Smith

et al. 2008

Molecular and Cellular Neuroscience

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Integrins regulate cytoplasmic calcium levels ([Ca 2+ ]i) in various cell types but information on activities in neurons is limited. The issue is of current interest because of evidence that both integrins and changes in [Ca 2+ ]i are required for Long-Term Potentiation. Accordingly, the present studies evaluated integrin ligand effects in cortical neurons. Integrin ligands or α5ß1 integrin activating antisera rapidly increased [Ca 2+ ]i with effects greater in glutamatergic than GABAergic neurons, absent in astroglia, and blocked by ß1 integrin neutralizing antisera and the tyrosine kinase antagonist genistein. Increases depended upon extracellular calcium and intracellular store release. Ligandinduced effects were reduced by voltage-sensitive calcium channel and NMDA receptor antagonists, but blocked by tetrodotoxin or AMPA receptor antagonists. These results indicate that integrin ligation triggers AMPA receptor/depolarization-dependent calcium influx followed by intracellular store release and suggest the possibility that integrin modulation of activity-induced changes in [Ca 2+ ]i contributes importantly to lasting synaptic plasticity in forebrain neurons.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores

Lin

Hilgenberg

Smith

et al. 2008

Molecular and Cellular Neuroscience

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“…Several studies indicate that calcium itself can convert synaptic activity into a transcription-regulating nuclear signal (37,(61)(62)(63). Calcium transients initiated by synaptic activity and calcium entry into neurons through ligand-and/or voltage-gated calcium channels in the dendritic tree as well as the cell soma invade the nucleus within milliseconds of the stimulation (37,63,64). In brain slices, synaptic inputs at distances of more than 150 m from the cell soma can generate robust calcium transients in the cell nucleus.…”

Section: Discussionmentioning

confidence: 99%

Diffusion and Not Active Transport Underlies and Limits ERK1/2 Synapse-to-Nucleus Signaling in Hippocampal Neurons

Wiegert

Bengtson

Bading

2007

Journal of Biological Chemistry

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The propagation of signals from synapses and dendrites to the nucleus is crucial for long lasting adaptive changes in the nervous system. The ERK-MAPK pathway can link neuronal activity and cell surface receptor activation to the regulation of gene transcription, and it is often considered the principal mediator of synapse-to-nucleus communication in late-phase plasticity and learning. However, the mechanisms underlying ERK1/2 trafficking in dendrites and nuclear translocation in neurons remain to be determined leaving it unclear whether ERK1/2 activated at the synapse can contribute to nuclear signaling and transcriptional regulation. Using the photobleachable and photoactivable fluorescent tag Dronpa on ERK1 and ERK2, we show here that ERK1/2 translocation to the nucleus of hippocampal neurons is induced by the stimulation of N-methyl-D-aspartate receptors or TrkB stimulation and is apparently mediated by facilitated diffusion. In contrast, ERK1/2 trafficking within dendrites is not signal-regulated and is mediated by passive diffusion. Within dendrites, the reach of a locally activated pool of ERK1/2 is very limited and follows an exponential decay with distance. These results indicate that successful signal propagation to the nucleus by the ERK-MAPK pathway depends on the distance of the nucleus from the site of ERK1/2 activation. ERK1/2 activated within or near the soma may rapidly reach the nucleus to induce gene expression, whereas ERK1/2 activated at distal synapses may only contribute to local signaling.The extracellular signal-regulated kinase/mitogen-activated protein (ERK-MAP) 2 kinase cascade is a multifunctional signaling module that plays an important role in the development, differentiation, and proliferation of many cell types. In the nervous system, ERK1 and ERK2 are activated by trophic factors, such as BDNF (1) and electrical activity causing calcium influx into neurons through NMDA receptors or voltage-gated calcium channels (2, 3). A large body of literature has implicated the ERK-MAP kinase pathway in numerous activity-driven neuronal processes, including neuronal survival, synaptic plasticity and learning (4, 5), circadian rhythms (6), pain (7), and addiction (8). ERK1/2 can act locally near the site of activation by cell surface receptors or ion channels to control, for example, the trafficking of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (9). Another putative role of ERK1/2 in the nervous system is to propagate signals generated at the synapse along the dendrites toward and into the cell nucleus, where it leads to induction of gene transcription. ERK1/2 can phosphorylate several transcription factors, including the ternary complex factors Elk-1 (10, 11) and SAP-1/2 (12), as well as c-Jun (13) and c-Fos (14). The cAMP-response element-binding protein (CREB) is also a target of the ERK-MAP kinase pathway, although CREB phosphorylation on its activator site serine 133 is catalyzed not by ERK1/2 but by the ERK1/2-regulated kinases ribosomal protein S6 kinase 2 and mitog...

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“…Nuclear calcium transients are triggered by calcium entry into neurons either through synaptic NMDA receptors or L-type voltage-gated calcium channels (Hardingham et al, 2001a(Hardingham et al, , 2002. Through a still unresolved mechanism, synaptic activity-induced calcium signals travel to the cell soma where they readily invade the nucleus most likely through NPCs (Nakazawa and Murphy, 1999;Hardingham et al, 2001a;Power and Sah, 2002;Raymond and Redman, 2006;Watanabe et al, 2006;Johenning and Holthoff, 2007;Eder andBading, 2007 Hagenston et al, 2008). In rat hippocampal neurons and amphibian sympathetic neurons, the nuclear compartment border does not sustain a calcium gradient across the nuclear envelope (O'Malley, 1994;Eder and Bading, 2007), although in other cell types the nucleus may be insulated from cytosolic calcium transients (al-Mohanna et al, 1994;Badminton et al, 1996).…”

Section: Infoldings Generate Nuclear Signaling Microdomainsmentioning

confidence: 99%

Synaptic Activity Induces Dramatic Changes in the Geometry of the Cell Nucleus: Interplay between Nuclear Structure, Histone H3 Phosphorylation, and Nuclear Calcium Signaling

Wittmann

Queisser²,

Eder³

et al. 2009

J. Neurosci.

120

159

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Synaptic activity initiates many adaptive responses in neurons. Here we report a novel form of structural plasticity in dissociated hippocampal cultures and slice preparations. Using a recently developed algorithm for three-dimensional image reconstruction and quantitative measurements of cell organelles, we found that many nuclei from hippocampal neurons are highly infolded and form unequally sized nuclear compartments. Nuclear infoldings are dynamic structures, which can radically transform the geometry of the nucleus in response to neuronal activity. Action potential bursting causing synaptic NMDA receptor activation dramatically increases the number of infolded nuclei via a process that requires the ERK-MAP kinase pathway and new protein synthesis. In contrast, deathsignaling pathways triggered by extrasynaptic NMDA receptors cause a rapid loss of nuclear infoldings. Compared with near-spherical nuclei, infolded nuclei have a larger surface and increased nuclear pore complex immunoreactivity. Nuclear calcium signals evoked by cytosolic calcium transients are larger in small nuclear compartments than in the large compartments of the same nucleus; moreover, small compartments are more efficient in temporally resolving calcium signals induced by trains of action potentials in the theta frequency range (5 Hz). Synaptic activity-induced phosphorylation of histone H3 on serine 10 was more robust in neurons with infolded nuclei compared with neurons with near-spherical nuclei, suggesting a functional link between nuclear geometry and transcriptional regulation. The translation of synaptic activity-induced signaling events into changes in nuclear geometry facilitates the relay of calcium signals to the nucleus, may lead to the formation of nuclear signaling microdomains, and could enhance signal-regulated transcription.

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Spatial segregation of neuronal calcium signals encodes different forms of LTP in rat hippocampus

Cited by 134 publications

References 59 publications

Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores

Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores

Diffusion and Not Active Transport Underlies and Limits ERK1/2 Synapse-to-Nucleus Signaling in Hippocampal Neurons

Synaptic Activity Induces Dramatic Changes in the Geometry of the Cell Nucleus: Interplay between Nuclear Structure, Histone H3 Phosphorylation, and Nuclear Calcium Signaling

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