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STDP in a bistable synapse model based on CaMKII and associated signaling pathways.

Publication ,  Journal Article
Graupner, M; Brunel, N
Published in: PLoS Comput Biol
November 2007

The calcium/calmodulin-dependent protein kinase II (CaMKII) plays a key role in the induction of long-term postsynaptic modifications following calcium entry. Experiments suggest that these long-term synaptic changes are all-or-none switch-like events between discrete states. 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. However, it is still unclear whether experimental LTP/LTD protocols lead to corresponding transitions between the two states in realistic models of such a network. We present a detailed biochemical model of the CaMKII autophosphorylation and the protein signaling cascade governing the CaMKII dephosphorylation. As previously shown, two stable states of the CaMKII phosphorylation level exist at resting intracellular calcium concentration, and high calcium transients can switch the system from the weakly phosphorylated (DOWN) to the highly phosphorylated (UP) state of the CaMKII (similar to a LTP event). We show here that increased CaMKII dephosphorylation activity at intermediate Ca(2+) concentrations can lead to switching from the UP to the DOWN state (similar to a LTD event). This can be achieved if protein phosphatase activity promoting CaMKII dephosphorylation activates at lower Ca(2+) levels than kinase activity. Finally, it is shown that the CaMKII system can qualitatively reproduce results of plasticity outcomes in response to spike-timing dependent plasticity (STDP) and presynaptic stimulation protocols. This shows that the CaMKII protein network can account for both induction, through LTP/LTD-like transitions, and storage, due to its bistability, of synaptic changes.

Duke Scholars

Published In

PLoS Comput Biol

DOI

EISSN

1553-7358

Publication Date

November 2007

Volume

3

Issue

11

Start / End Page

e221

Location

United States

Related Subject Headings

  • Synaptic Transmission
  • Synapses
  • Signal Transduction
  • Neurons
  • Neuronal Plasticity
  • Nerve Net
  • Models, Neurological
  • Memory
  • Long-Term Synaptic Depression
  • Long-Term Potentiation
 

Citation

APA
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MLA
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Graupner, M., & Brunel, N. (2007). STDP in a bistable synapse model based on CaMKII and associated signaling pathways. PLoS Comput Biol, 3(11), e221. https://doi.org/10.1371/journal.pcbi.0030221
Graupner, Michael, and Nicolas Brunel. “STDP in a bistable synapse model based on CaMKII and associated signaling pathways.PLoS Comput Biol 3, no. 11 (November 2007): e221. https://doi.org/10.1371/journal.pcbi.0030221.
Graupner M, Brunel N. STDP in a bistable synapse model based on CaMKII and associated signaling pathways. PLoS Comput Biol. 2007 Nov;3(11):e221.
Graupner, Michael, and Nicolas Brunel. “STDP in a bistable synapse model based on CaMKII and associated signaling pathways.PLoS Comput Biol, vol. 3, no. 11, Nov. 2007, p. e221. Pubmed, doi:10.1371/journal.pcbi.0030221.
Graupner M, Brunel N. STDP in a bistable synapse model based on CaMKII and associated signaling pathways. PLoS Comput Biol. 2007 Nov;3(11):e221.

Published In

PLoS Comput Biol

DOI

EISSN

1553-7358

Publication Date

November 2007

Volume

3

Issue

11

Start / End Page

e221

Location

United States

Related Subject Headings

  • Synaptic Transmission
  • Synapses
  • Signal Transduction
  • Neurons
  • Neuronal Plasticity
  • Nerve Net
  • Models, Neurological
  • Memory
  • Long-Term Synaptic Depression
  • Long-Term Potentiation