期刊
PLOS COMPUTATIONAL BIOLOGY
卷 12, 期 5, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pcbi.1004949
关键词
-
资金
- Engineering and Physical Sciences Research Council (EPSRC) [EP/I013717/1]
- EPSRC [EP/L000296/1, EP/N014391/1]
- Biotechnology and Biological Sciences Research Council
- Wellcome Trust
- Wellcome Trust [101029/Z/13/Z] Funding Source: Wellcome Trust
- BBSRC [BB/K000454/1, BB/N013956/1] Funding Source: UKRI
- EPSRC [EP/L000296/1, EP/N014391/1, EP/I018638/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/K000454/1, BB/N013956/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [1098663, EP/N014391/1, EP/I018638/1, EP/L000296/1] Funding Source: researchfish
- Wellcome Trust [101029/Z/13/Z] Funding Source: researchfish
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据