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J Comput Neurosci. 2015 Dec;39(3):329-47. doi: 10.1007/s10827-015-0579-z. Epub 2015 Oct 24.

Ryanodine-receptor-driven intracellular calcium dynamics underlying spatial association of synaptic plasticity.

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Graduate School of Information Science and Engineering, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan.
Department of Human and Computer Intelligence, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan.


Synaptic modifications induced at one synapse are accompanied by hetero-synaptic changes at neighboring sites. In addition, it is suggested that the mechanism of spatial association of synaptic plasticity is based on intracellular calcium signaling that is mainly regulated by two types of receptors of endoplasmic reticulum calcium store: the ryanodine receptor (RyR) and the inositol triphosphate receptor (IP3R). However, it is not clear how these types of receptors regulate intracellular calcium flux and contribute to the outcome of calcium-dependent synaptic change. To understand the relation between the synaptic association and store-regulated calcium dynamics, we focused on the function of RyR calcium regulation and simulated its behavior by using a computational neuron model. As a result, we observed that RyR-regulated calcium release depended on spike timings of pre- and postsynaptic neurons. From the induction site of calcium release, the chain activation of RyRs occurred, and spike-like calcium increase propagated along the dendrite. For calcium signaling, the propagated calcium increase did not tend to attenuate; these characteristics came from an all-or-none behavior of RyR-sensitive calcium store. Considering the role of calcium dependent synaptic plasticity, the results suggest that RyR-regulated calcium propagation induces a similar change at the synapses. However, according to the dependence of RyR calcium regulation on the model parameters, whether the chain activation of RyRs occurred, sensitively depended on spatial expression of RyR and nominal fluctuation of calcium flux. Therefore, calcium regulation of RyR helps initiate rather than relay calcium propagation.


Calcium signaling; Intracellular; Ryanodine receptor; Simulation

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