Calcium-based plasticity model explains sensitivity of synaptic changes to spike pattern, rate, and dendritic location

Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3991-6. doi: 10.1073/pnas.1109359109. Epub 2012 Feb 22.


Multiple stimulation protocols have been found to be effective in changing synaptic efficacy by inducing long-term potentiation or depression. In many of those protocols, increases in postsynaptic calcium concentration have been shown to play a crucial role. However, it is still unclear whether and how the dynamics of the postsynaptic calcium alone determine the outcome of synaptic plasticity. Here, we propose a calcium-based model of a synapse in which potentiation and depression are activated above calcium thresholds. We show that this model gives rise to a large diversity of spike timing-dependent plasticity curves, most of which have been observed experimentally in different systems. It accounts quantitatively for plasticity outcomes evoked by protocols involving patterns with variable spike timing and firing rate in hippocampus and neocortex. Furthermore, it allows us to predict that differences in plasticity outcomes in different studies are due to differences in parameters defining the calcium dynamics. The model provides a mechanistic understanding of how various stimulation protocols provoke specific synaptic changes through the dynamics of calcium concentration and thresholds implementing in simplified fashion protein signaling cascades, leading to long-term potentiation and long-term depression. The combination of biophysical realism and analytical tractability makes it the ideal candidate to study plasticity at the synapse, neuron, and network levels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / chemistry
  • Calcium / metabolism*
  • Calcium Signaling
  • Computer Simulation
  • Dendrites / metabolism*
  • Hippocampus / physiology
  • Humans
  • Long-Term Potentiation
  • Long-Term Synaptic Depression
  • Models, Biological
  • Models, Statistical
  • Neocortex / physiology
  • Neuronal Plasticity / physiology*
  • Synapses / metabolism*
  • Synaptic Transmission


  • Calcium