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Publication - Dr Thom Griffith

    Control of Ca2+ influx and calmodulin activation by SK-channels in dendritic spines

    Citation

    Griffith, TJO, Tsaneva-Atanasova, K & Mellor, J, 2016, ‘Control of Ca2+ influx and calmodulin activation by SK-channels in dendritic spines’. PLoS Computational Biology, vol 12.

    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 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.

    Full details in the University publications repository