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STDP in a bistable synapse model based on CaMKII and associated signaling pathways
Michael Graupner1, Nicolas Brunel
1Université Paris Descartes, Laboratoire de Neurophysique et Physiologie, Paris, France. michael.graupner@univ-paris5.fr
Plos Computational Biology
|December 7, 2007
Summary
Calcium/calmodulin-dependent protein kinase II (CaMKII) acts as a bistable switch for synaptic plasticity. This study models how CaMKII transitions between states, explaining long-term potentiation and depression, and storing synaptic changes.
Area of Science:
- Neuroscience
- Biochemistry
- Computational Biology
Background:
- Calcium/calmodulin-dependent protein kinase II (CaMKII) is crucial for synaptic plasticity.
- Synaptic changes are thought to be switch-like events.
- A CaMKII-based biochemical network is hypothesized to act as a bistable switch for synaptic states.
Purpose of the Study:
- To investigate if CaMKII network models can explain transitions between synaptic states induced by LTP/LTD protocols.
- To model the CaMKII autophosphorylation and dephosphorylation cascade.
- To determine if the CaMKII system can reproduce plasticity outcomes under STDP and presynaptic stimulation.
Main Methods:
- Developed a detailed biochemical model of CaMKII autophosphorylation and dephosphorylation.
- Simulated CaMKII system behavior under varying calcium concentrations.
- Analyzed model responses to simulated LTP/LTD induction and STDP protocols.
Main Results:
- Confirmed two stable CaMKII phosphorylation states (UP and DOWN) at resting calcium levels.
- Demonstrated that high calcium transients induce a switch from DOWN to UP state (LTP-like).
- Showed that increased dephosphorylation activity at intermediate calcium levels can switch UP to DOWN state (LTD-like), dependent on phosphatase activation kinetics.
- Validated that the CaMKII model qualitatively reproduces plasticity outcomes for STDP and presynaptic stimulation.
Conclusions:
- The CaMKII biochemical network can function as a bistable switch, explaining synaptic plasticity induction.
- The model supports the hypothesis that CaMKII network dynamics underlie both the induction and stable storage of synaptic modifications.
- CaMKII's ability to transition between states and maintain them is key to synaptic memory formation.
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