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This article is part of the supplement: Sixteenth Annual Computational Neuroscience Meeting: CNS*2007

Open Access Poster presentation

Induction and binary expression of LTP/LTD in a minimal model of the CaMKII system

Michael Graupner12* and Nicolas Brunel1

Author Affiliations

1 Laboratoire de Neurophysique et Physiologie, CNRS UMR 8119, Université Paris Descartes – Paris V, 45, rue des Saints Pères, 75270 Paris Cedex 06, France

2 Max-Planck-Institut für Physik komplexer Systeme, Nötnitzer Straße 38, 01187 Dresden, Germany

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BMC Neuroscience 2007, 8(Suppl 2):P94  doi:10.1186/1471-2202-8-S2-P94

The electronic version of this article is the complete one and can be found online at:

Published:6 July 2007

© 2007 Graupner and Brunel; licensee BioMed Central Ltd.

Poster presentation

The calcium/calmodulin-dependent protein kinase II (CaMKII) plays a key role in the induction of long-term post-synaptic modifications following synaptic activation. Experiments suggest that these long-term synaptic changes are all-or none switch-like events between discrete states [1]. The biochemical network involving CaMKII and its regulating protein signaling cascade has been hypothesized to durably maintain the evoked synaptic state in the form of a bistable switch [2,3]. However, it is still unclear whether different experimental LTP/LTD protocols lead to corresponding transitions between the two states in models of such a network. Furthermore, the biochemical mechanisms and signaling cascades giving rise to the non-linearities exhibited during LTP/LTD induction remain elusive.

Starting from a detailed biochemical model, a minimal model describing the CaMKII phosphorylation (activation) level is presented which preserves the features of a comprehensive description. CaMKII autophosphorylation is governed by calcium/calmodulin binding and is a highly cooperative process. CaMKII dephosphorylation is mediated by protein phosphatase 1 whose activity is indirectly regulated by a calcium-dependent balance of kinase (protein kinase A) and phosphatase (calcineurin) activity. These two competing effects are implemented via phosphorylation- and dephosphorylation rates changing the CaMKII phosphorylation level and are realized as simple step functions activating above different calcium levels.

The model retains previous results [2,3], two stable states of CaMKII phosphorylation exist at resting intracellular calcium concentrations. With an appropriate positioning of the de-/phosphorylation thresholds, high calcium transients can switch the system from the weakly-(DOWN) to the highly-phosphorylated (UP) state of the CaMKII (similar to a LTP event) and intermediate Ca(2+) concentrations can lead to switching from the UP to the DOWN state (similar to a LTD event). As a basic principle, this can be achieved if the CaMKII dephosphorylation activates at lower Ca(2+) levels than phosphorylation. This simple approach allows us to address whether or not a read-out system using the calcium level as the sole input signal can account for the non-linearities exhibited during LTP/LTD induction. It is shown that this simple realization of the CaMKII system can qualitatively reproduce experimental plasticity results in response to spike-timing dependent plasticity (STDP) protocols (spike-pairs and -triplets), pre-synaptic stimulation protocols and pairing protocols. Our investigations show that a minimal model of the CaMKII protein network can account for both induction (through LTP/LTD-like transitions) and storage (due to its bistability) of synaptic changes. However, we suggest that the dynamics of the global calcium time course play a crucial role for the sign of synaptic changes alongside the crosstalk between signaling cascades that include the one considered here.


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    Proc Natl Acad Sci USA 2005, 102:9679-84. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  2. Zhabotinsky AM: Bistability in the Ca(2+)/calmodulin-dependent protein kinase-phosphatase system.

    Biophys J 2000, 79:2211-2221. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

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    Biol Cybern 2000, 82:35-47. PubMed Abstract | Publisher Full Text OpenURL