Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines.
The key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR) and voltage-gated Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction of synaptic plasticity by...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-05-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC4883788?pdf=render |
| _version_ | 1818024236435898368 |
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| author | Thom Griffith Krasimira Tsaneva-Atanasova Jack R Mellor |
| author_facet | Thom Griffith Krasimira Tsaneva-Atanasova Jack R Mellor |
| author_sort | Thom Griffith |
| collection | DOAJ |
| description | The key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR) and voltage-gated Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction of synaptic plasticity by differential activation of Ca2+ -sensitive enzymes such as calmodulin. Ca2+ influx is negatively regulated by Ca2+ -activated K+ channels (SK-channels) which are in turn inhibited by neuromodulators such as acetylcholine. However, the precise mechanisms by which SK-channels control the induction of synaptic plasticity remain unclear. Using a 3-dimensional model of Ca2+ and calmodulin dynamics within an idealised, but biophysically-plausible, dendritic spine, we show that SK-channels regulate calmodulin activation specifically during neuron-firing patterns associated with induction of spike timing-dependent plasticity. SK-channel activation and the subsequent reduction in Ca2+ influx through NMDARs and L-type VGCCs results in an order of magnitude decrease in calmodulin (CaM) activation, providing a mechanism for the effective gating of synaptic plasticity induction. This provides a common mechanism for the regulation of synaptic plasticity by neuromodulators. |
| first_indexed | 2024-12-10T03:57:00Z |
| format | Article |
| id | doaj.art-7fc502183c7d4d768d3a0831be999f7e |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-10T03:57:00Z |
| publishDate | 2016-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-7fc502183c7d4d768d3a0831be999f7e2022-12-22T02:03:06ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582016-05-01125e100494910.1371/journal.pcbi.1004949Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines.Thom GriffithKrasimira Tsaneva-AtanasovaJack R MellorThe key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR) and voltage-gated Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction of synaptic plasticity by differential activation of Ca2+ -sensitive enzymes such as calmodulin. Ca2+ influx is negatively regulated by Ca2+ -activated K+ channels (SK-channels) which are in turn inhibited by neuromodulators such as acetylcholine. However, the precise mechanisms by which SK-channels control the induction of synaptic plasticity remain unclear. Using a 3-dimensional model of Ca2+ and calmodulin dynamics within an idealised, but biophysically-plausible, dendritic spine, we show that SK-channels regulate calmodulin activation specifically during neuron-firing patterns associated with induction of spike timing-dependent plasticity. SK-channel activation and the subsequent reduction in Ca2+ influx through NMDARs and L-type VGCCs results in an order of magnitude decrease in calmodulin (CaM) activation, providing a mechanism for the effective gating of synaptic plasticity induction. This provides a common mechanism for the regulation of synaptic plasticity by neuromodulators.http://europepmc.org/articles/PMC4883788?pdf=render |
| spellingShingle | Thom Griffith Krasimira Tsaneva-Atanasova Jack R Mellor Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines. PLoS Computational Biology |
| title | Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines. |
| title_full | Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines. |
| title_fullStr | Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines. |
| title_full_unstemmed | Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines. |
| title_short | Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines. |
| title_sort | control of ca2 influx and calmodulin activation by sk channels in dendritic spines |
| url | http://europepmc.org/articles/PMC4883788?pdf=render |
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