The Experts below are selected from a list of 17187 Experts worldwide ranked by ideXlab platform
Patricia C. Salinas - One of the best experts on this subject based on the ideXlab platform.
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wnt7a signaling promotes dendritic spine growth and Synaptic Strength through ca2 calmodulin dependent protein kinase ii
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Lorenza Ciani, Kieran A. Boyle, Ellen M. Dickins, Macarena Sahores, Derek Anane, Douglas M. Lopes, Alasdair J. Gibb, Patricia C. SalinasAbstract:The balance between excitatory and inhibitory synapses is crucial for normal brain function. Wnt proteins stimulate synapse formation by increasing Synaptic assembly. However, it is unclear whether Wnt signaling differentially regulates the formation of excitatory and inhibitory synapses. Here, we demonstrate that Wnt7a preferentially stimulates excitatory synapse formation and function. In hippocampal neurons, Wnt7a increases the number of excitatory synapses, whereas inhibitory synapses are unaffected. Wnt7a or postSynaptic expression of Dishevelled-1 (Dvl1), a core Wnt signaling component, increases the frequency and amplitude of miniature excitatory postSynaptic currents (mEPSCs), but not miniature inhibitory postSynaptic currents (mIPSCs). Wnt7a increases the density and maturity of dendritic spines, whereas Wnt7a-Dvl1-deficient mice exhibit defects in spine morphogenesis and mossy fiber-CA3 Synaptic transmission in the hippocampus. Using a postSynaptic reporter for Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) activity, we demonstrate that Wnt7a rapidly activates CaMKII in spines. Importantly, CaMKII inhibition abolishes the effects of Wnt7a on spine growth and excitatory Synaptic Strength. These data indicate that Wnt7a signaling is critical to regulate spine growth and Synaptic Strength through the local activation of CaMKII at dendritic spines. Therefore, aberrant Wnt7a signaling may contribute to neurological disorders in which excitatory signaling is disrupted.
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Wnt7a signaling promotes dendritic spine growth and Synaptic Strength through Ca2+/Calmodulin-dependent protein kinase II
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Lorenza Ciani, Kieran A. Boyle, Ellen M. Dickins, Macarena Sahores, Derek Anane, Douglas M. Lopes, Alasdair J. Gibb, Patricia C. SalinasAbstract:The balance between excitatory and inhibitory synapses is crucial for normal brain function. Wnt proteins stimulate synapse formation by increasing Synaptic assembly. However, it is unclear whether Wnt signaling differentially regulates the formation of excitatory and inhibitory synapses. Here, we demonstrate that Wnt7a preferentially stimulates excitatory synapse formation and function. In hippocampal neurons, Wnt7a increases the number of excitatory synapses, whereas inhibitory synapses are unaffected. Wnt7a or postSynaptic expression of Dishevelled-1 (Dvl1), a core Wnt signaling component, increases the frequency and amplitude of miniature excitatory postSynaptic currents (mEPSCs), but not miniature inhibitory postSynaptic currents (mIPSCs). Wnt7a increases the density and maturity of dendritic spines, whereas Wnt7a-Dvl1-deficient mice exhibit defects in spine morphogenesis and mossy fiber-CA3 Synaptic transmission in the hippocampus. Using a postSynaptic reporter for Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) activity, we demonstrate that Wnt7a rapidly activates CaMKII in spines. Importantly, CaMKII inhibition abolishes the effects of Wnt7a on spine growth and excitatory Synaptic Strength. These data indicate that Wnt7a signaling is critical to regulate spine growth and Synaptic Strength through the local activation of CaMKII at dendritic spines. Therefore, aberrant Wnt7a signaling may contribute to neurological disorders in which excitatory signaling is disrupted.
Lorenza Ciani - One of the best experts on this subject based on the ideXlab platform.
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wnt7a signaling promotes dendritic spine growth and Synaptic Strength through ca2 calmodulin dependent protein kinase ii
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Lorenza Ciani, Kieran A. Boyle, Ellen M. Dickins, Macarena Sahores, Derek Anane, Douglas M. Lopes, Alasdair J. Gibb, Patricia C. SalinasAbstract:The balance between excitatory and inhibitory synapses is crucial for normal brain function. Wnt proteins stimulate synapse formation by increasing Synaptic assembly. However, it is unclear whether Wnt signaling differentially regulates the formation of excitatory and inhibitory synapses. Here, we demonstrate that Wnt7a preferentially stimulates excitatory synapse formation and function. In hippocampal neurons, Wnt7a increases the number of excitatory synapses, whereas inhibitory synapses are unaffected. Wnt7a or postSynaptic expression of Dishevelled-1 (Dvl1), a core Wnt signaling component, increases the frequency and amplitude of miniature excitatory postSynaptic currents (mEPSCs), but not miniature inhibitory postSynaptic currents (mIPSCs). Wnt7a increases the density and maturity of dendritic spines, whereas Wnt7a-Dvl1-deficient mice exhibit defects in spine morphogenesis and mossy fiber-CA3 Synaptic transmission in the hippocampus. Using a postSynaptic reporter for Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) activity, we demonstrate that Wnt7a rapidly activates CaMKII in spines. Importantly, CaMKII inhibition abolishes the effects of Wnt7a on spine growth and excitatory Synaptic Strength. These data indicate that Wnt7a signaling is critical to regulate spine growth and Synaptic Strength through the local activation of CaMKII at dendritic spines. Therefore, aberrant Wnt7a signaling may contribute to neurological disorders in which excitatory signaling is disrupted.
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Wnt7a signaling promotes dendritic spine growth and Synaptic Strength through Ca2+/Calmodulin-dependent protein kinase II
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Lorenza Ciani, Kieran A. Boyle, Ellen M. Dickins, Macarena Sahores, Derek Anane, Douglas M. Lopes, Alasdair J. Gibb, Patricia C. SalinasAbstract:The balance between excitatory and inhibitory synapses is crucial for normal brain function. Wnt proteins stimulate synapse formation by increasing Synaptic assembly. However, it is unclear whether Wnt signaling differentially regulates the formation of excitatory and inhibitory synapses. Here, we demonstrate that Wnt7a preferentially stimulates excitatory synapse formation and function. In hippocampal neurons, Wnt7a increases the number of excitatory synapses, whereas inhibitory synapses are unaffected. Wnt7a or postSynaptic expression of Dishevelled-1 (Dvl1), a core Wnt signaling component, increases the frequency and amplitude of miniature excitatory postSynaptic currents (mEPSCs), but not miniature inhibitory postSynaptic currents (mIPSCs). Wnt7a increases the density and maturity of dendritic spines, whereas Wnt7a-Dvl1-deficient mice exhibit defects in spine morphogenesis and mossy fiber-CA3 Synaptic transmission in the hippocampus. Using a postSynaptic reporter for Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) activity, we demonstrate that Wnt7a rapidly activates CaMKII in spines. Importantly, CaMKII inhibition abolishes the effects of Wnt7a on spine growth and excitatory Synaptic Strength. These data indicate that Wnt7a signaling is critical to regulate spine growth and Synaptic Strength through the local activation of CaMKII at dendritic spines. Therefore, aberrant Wnt7a signaling may contribute to neurological disorders in which excitatory signaling is disrupted.
Dieter Bruns - One of the best experts on this subject based on the ideXlab platform.
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Astrocytes control Synaptic Strength by two distinct v-SNARE-dependent release pathways
Nature Neuroscience, 2017Co-Authors: Yvonne Schwarz, Na Zhao, Frank Kirchhoff, Dieter BrunsAbstract:Communication between glia cells and neurons is crucial for brain functions, but the molecular mechanisms and functional consequences of gliotransmission remain enigmatic. Here we report that astrocytes express synaptobrevin II and cellubrevin as functionally non-overlapping vesicular SNARE proteins on glutamatergic vesicles and neuropeptide Y-containing large dense-core vesicles, respectively. Using individual null-mutants for Vamp2 (synaptobrevin II) and Vamp3 (cellubrevin), as well as the corresponding compound null-mutant for genes encoding both v-SNARE proteins, we delineate previously unrecognized individual v-SNARE dependencies of astrocytic release processes and their functional impact on neuronal signaling. Specifically, we show that astroglial cellubrevin-dependent neuropeptide Y secretion diminishes Synaptic signaling, while synaptobrevin II–dependent glutamate release from astrocytes enhances Synaptic signaling. Our experiments thereby uncover the molecular mechanisms of two distinct v-SNARE-dependent astrocytic release pathways that oppositely control Synaptic Strength at preSynaptic sites, elucidating new avenues of communication between astrocytes and neurons. The mechanisms of gliotransmitter release and their impact on neuronal signaling have remained largely elusive. The authors describe two functionally non-overlapping v-SNARE-dependent astrocytic release pathways that oppositely control Synaptic Strength at preSynaptic sites. Thus, astrocytes are able to fine-tune fast glutamatergic neurotransmission and control fundamental processes of Synaptic communication.
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Astrocytes control Synaptic Strength by two distinct v-SNARE-dependent release pathways.
Nature Neuroscience, 2017Co-Authors: Yvonne Schwarz, Na Zhao, Frank Kirchhoff, Dieter BrunsAbstract:Communication between glia cells and neurons is crucial for brain functions, but the molecular mechanisms and functional consequences of gliotransmission remain enigmatic. Here we report that astrocytes express synaptobrevin II and cellubrevin as functionally non-overlapping vesicular SNARE proteins on glutamatergic vesicles and neuropeptide Y-containing large dense-core vesicles, respectively. Using individual null-mutants for Vamp2 (synaptobrevin II) and Vamp3 (cellubrevin), as well as the corresponding compound null-mutant for genes encoding both v-SNARE proteins, we delineate previously unrecognized individual v-SNARE dependencies of astrocytic release processes and their functional impact on neuronal signaling. Specifically, we show that astroglial cellubrevin-dependent neuropeptide Y secretion diminishes Synaptic signaling, while synaptobrevin II-dependent glutamate release from astrocytes enhances Synaptic signaling. Our experiments thereby uncover the molecular mechanisms of two distinct v-SNARE-dependent astrocytic release pathways that oppositely control Synaptic Strength at preSynaptic sites, elucidating new avenues of communication between astrocytes and neurons.
John E. Lisman - One of the best experts on this subject based on the ideXlab platform.
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memory formation depends on both synapse specific modifications of Synaptic Strength and cell specific increases in excitability
Nature Neuroscience, 2018Co-Authors: John E. Lisman, Katherine Cooper, Megha Sehgal, Alcino J SilvaAbstract:The modification of Synaptic Strength produced by long-term potentiation (LTP) is widely thought to underlie memory storage. Indeed, given that hippocampal pyramidal neurons have >10,000 independently modifiable synapses, the potential for information storage by Synaptic modification is enormous. However, recent work suggests that CREB-mediated global changes in neuronal excitability also play a critical role in memory formation. Because these global changes have a modest capacity for information storage compared with that of Synaptic plasticity, their importance for memory function has been unclear. Here we review the newly emerging evidence for CREB-dependent control of excitability and discuss two possible mechanisms. First, the CREB-dependent transient change in neuronal excitability performs a memory-allocation function ensuring that memory is stored in ways that facilitate effective linking of events with temporal proximity (hours). Second, these changes may promote cell-assembly formation during the memory-consolidation phase. It has been unclear whether such global excitability changes and local Synaptic mechanisms are complementary. Here we argue that the two mechanisms can work together to promote useful memory function.
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Catalytically Dead αCaMKII K42M Mutant Acts as a Dominant Negative in the Control of Synaptic Strength
PloS one, 2015Co-Authors: Anatoli Y. Kabakov, John E. LismanAbstract:During long-term potentiation (LTP) of excitatory synapses, Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated by Ca2+ influx through NMDA receptors that potentiate AMPA receptor currents by insertion of additional GluR1-containing receptors at the synapse and by increasing AMPA channel conductance, as well as by stimulating structural changes. CaMKII is also involved in the maintenance of LTP and contributes to maintenance of behavioral sensitization by cocaine or amphetamine. Recent studies show that transient expression of catalytically dead αCaMKII K42M mutant after exposure to amphetamine persistently reverses the behavioral effects of the addiction. A suggested interpretation is that this mutant acts as a dominant negative in the control of Synaptic Strength, but this interpretation has not been physiologically tested. Here we investigate the effect of αCaMKII K42M mutant expressed in single CA1 pyramidal neurons on basal excitatory neurotransmission in cultured rat hippocampal organotypic slices. The mutant caused nearly 50% reduction in the basal CA3–CA1 transmission, while overexpression of the wild-type αCaMKII had no effect. This result is consistent with the dominant negative hypothesis, but there are complexities. We found that the decrease in basal transmission did not occur when activity in the slices was suppressed after transfection by TTX or when NMDA receptors were blocked by APV. Thus, the dominant negative effect requires neural activity for its expression.
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Activity-dependent regulation of Synaptic Strength by PSD-95 in CA1 neurons
Journal of neurophysiology, 2011Co-Authors: Peng Zhang, John E. LismanAbstract:CaMKII and PSD-95 are the two most abundant postSynaptic proteins in the postSynaptic density (PSD). Overexpression of either can dramatically increase Synaptic Strength and saturate long-term pote...
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Role of the CaMKII/NMDA Receptor Complex in the Maintenance of Synaptic Strength
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011Co-Authors: Magdalena Sanhueza, Johannes W. Hell, Nikolai Otmakhov, Fernandez-villalobos G, Ivar S. Stein, Gyulnara G. Kasumova, Zhang P, John E. LismanAbstract:During long-term potentiation (LTP), synapses undergo stable changes in Synaptic Strength. The molecular memory processes that maintain Strength have not been identified. One hypothesis is that the complex formed by the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the NMDA-type glutamate receptor (NMDAR) is a molecular memory at the synapse. To establish a molecule as a molecular memory, it must be shown that interfering with the molecule produces a persistent reversal of LTP. We used the CN class of peptides that inhibit CaMKII binding to the NR2B subunit in vitro to test this prediction in rat hippocampal slices. We found that CN peptides can reverse saturated LTP, allowing additional LTP to be induced. The peptide also produced a persistent reduction in basal transmission. We then tested whether CN compounds actually affect CaMKII binding in living cells. Application of CN peptide to slice cultures reduced the amount of CaMKII concentrated in spines, consistent with delocalization of the kinase from a binding partner in the spine. To more specifically assay the binding of CaMKII to the NMDAR, we used coimmunoprecipitation methods. We found that CN peptide decreased Synaptic Strength only at concentrations necessary to disrupt the CaMKII/NMDAR complex, but not at lower concentrations sufficient to inhibit CaMKII activity. Importantly, both the reduction of the complex and the reduction of Synaptic Strength persisted after removal of the inhibitor. These results support the hypothesis that the CaMKII/NMDAR complex has switch-like properties that are important in the maintenance of Synaptic Strength.
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role of the camkii nmda receptor complex in the maintenance of Synaptic Strength
The Journal of Neuroscience, 2011Co-Authors: Magdalena Sanhueza, Johannes W. Hell, K. Ulrich Bayer, Nikolai Otmakhov, Ivar S. Stein, Gyulnara G. Kasumova, G Fernandezvillalobos, P Zhang, John E. LismanAbstract:During long-term potentiation (LTP), synapses undergo stable changes in Synaptic Strength. The molecular memory processes that maintain Strength have not been identified. One hypothesis is that the complex formed by the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the NMDA-type glutamate receptor (NMDAR) is a molecular memory at the synapse. To establish a molecule as a molecular memory, it must be shown that interfering with the molecule produces a persistent reversal of LTP. We used the CN class of peptides that inhibit CaMKII binding to the NR2B subunit in vitro to test this prediction in rat hippocampal slices. We found that CN peptides can reverse saturated LTP, allowing additional LTP to be induced. The peptide also produced a persistent reduction in basal transmission. We then tested whether CN compounds actually affect CaMKII binding in living cells. Application of CN peptide to slice cultures reduced the amount of CaMKII concentrated in spines, consistent with delocalization of the kinase from a binding partner in the spine. To more specifically assay the binding of CaMKII to the NMDAR, we used coimmunoprecipitation methods. We found that CN peptide decreased Synaptic Strength only at concentrations necessary to disrupt the CaMKII/NMDAR complex, but not at lower concentrations sufficient to inhibit CaMKII activity. Importantly, both the reduction of the complex and the reduction of Synaptic Strength persisted after removal of the inhibitor. These results support the hypothesis that the CaMKII/NMDAR complex has switch-like properties that are important in the maintenance of Synaptic Strength.
Douglas M. Lopes - One of the best experts on this subject based on the ideXlab platform.
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wnt7a signaling promotes dendritic spine growth and Synaptic Strength through ca2 calmodulin dependent protein kinase ii
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Lorenza Ciani, Kieran A. Boyle, Ellen M. Dickins, Macarena Sahores, Derek Anane, Douglas M. Lopes, Alasdair J. Gibb, Patricia C. SalinasAbstract:The balance between excitatory and inhibitory synapses is crucial for normal brain function. Wnt proteins stimulate synapse formation by increasing Synaptic assembly. However, it is unclear whether Wnt signaling differentially regulates the formation of excitatory and inhibitory synapses. Here, we demonstrate that Wnt7a preferentially stimulates excitatory synapse formation and function. In hippocampal neurons, Wnt7a increases the number of excitatory synapses, whereas inhibitory synapses are unaffected. Wnt7a or postSynaptic expression of Dishevelled-1 (Dvl1), a core Wnt signaling component, increases the frequency and amplitude of miniature excitatory postSynaptic currents (mEPSCs), but not miniature inhibitory postSynaptic currents (mIPSCs). Wnt7a increases the density and maturity of dendritic spines, whereas Wnt7a-Dvl1-deficient mice exhibit defects in spine morphogenesis and mossy fiber-CA3 Synaptic transmission in the hippocampus. Using a postSynaptic reporter for Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) activity, we demonstrate that Wnt7a rapidly activates CaMKII in spines. Importantly, CaMKII inhibition abolishes the effects of Wnt7a on spine growth and excitatory Synaptic Strength. These data indicate that Wnt7a signaling is critical to regulate spine growth and Synaptic Strength through the local activation of CaMKII at dendritic spines. Therefore, aberrant Wnt7a signaling may contribute to neurological disorders in which excitatory signaling is disrupted.
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Wnt7a signaling promotes dendritic spine growth and Synaptic Strength through Ca2+/Calmodulin-dependent protein kinase II
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Lorenza Ciani, Kieran A. Boyle, Ellen M. Dickins, Macarena Sahores, Derek Anane, Douglas M. Lopes, Alasdair J. Gibb, Patricia C. SalinasAbstract:The balance between excitatory and inhibitory synapses is crucial for normal brain function. Wnt proteins stimulate synapse formation by increasing Synaptic assembly. However, it is unclear whether Wnt signaling differentially regulates the formation of excitatory and inhibitory synapses. Here, we demonstrate that Wnt7a preferentially stimulates excitatory synapse formation and function. In hippocampal neurons, Wnt7a increases the number of excitatory synapses, whereas inhibitory synapses are unaffected. Wnt7a or postSynaptic expression of Dishevelled-1 (Dvl1), a core Wnt signaling component, increases the frequency and amplitude of miniature excitatory postSynaptic currents (mEPSCs), but not miniature inhibitory postSynaptic currents (mIPSCs). Wnt7a increases the density and maturity of dendritic spines, whereas Wnt7a-Dvl1-deficient mice exhibit defects in spine morphogenesis and mossy fiber-CA3 Synaptic transmission in the hippocampus. Using a postSynaptic reporter for Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) activity, we demonstrate that Wnt7a rapidly activates CaMKII in spines. Importantly, CaMKII inhibition abolishes the effects of Wnt7a on spine growth and excitatory Synaptic Strength. These data indicate that Wnt7a signaling is critical to regulate spine growth and Synaptic Strength through the local activation of CaMKII at dendritic spines. Therefore, aberrant Wnt7a signaling may contribute to neurological disorders in which excitatory signaling is disrupted.
