dc.contributor.author | Griffith, T | |
dc.contributor.author | Tsaneva-Atanasova, K | |
dc.contributor.author | Mellor, JR | |
dc.date.accessioned | 2016-05-31T08:21:18Z | |
dc.date.issued | 2016-05-27 | |
dc.description.abstract | 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 voltagegated
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. | en_GB |
dc.description.sponsorship | TG was supported by Engineering and
Physical Sciences Research Council (EPSRC) grant
EP/I013717/1. KTA was supported by grants EP/
L000296/1 and EP/N014391/1 of EPSRC. JRM was
supported by Biotechnology and Biological Sciences
Research Council and Wellcome Trust. | en_GB |
dc.identifier.citation | PLoS Computational Biology, 2016, Vol. 12(5): e1004949 | en_GB |
dc.identifier.doi | 10.1371/journal.pcbi.1004949 | |
dc.identifier.uri | http://hdl.handle.net/10871/21745 | |
dc.language.iso | en | en_GB |
dc.publisher | Public Library of Science | en_GB |
dc.relation.url | http://dx.doi.org/10.1371/journal.pcbi.1004949 | en_GB |
dc.relation.url | http://hdl.handle.net/10871/21394 | en_GB |
dc.rights | This is the final version of the article. Available from PLoS via the DOI in this record. | en_GB |
dc.title | Control of Ca2+ influx and calmodulin activation by SK-channels in dendritic spines (article) | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2016-05-31T08:21:18Z | |
dc.identifier.issn | 1553-734X | |
dc.description | Dataset available at: http://hdl.handle.net/10871/21394 | en_GB |
dc.identifier.journal | PLoS Computational Biology | en_GB |