A 3-dimensional model of Ca2+ and calmodulin dynamics within an idealised, but biophysically-plausible,
dendritic spine, demonstrates that SK-channels regulate calmodulin activation specifically during neurone firing patterns associated with induction of spike timing-dependent plasticity.The journal article associated with this dataset is available at: http://hdl.handle.net/10871/21745.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
