A Ca 2+-based computational model for NMDA receptordependent synaptic plasticity at individual post-synaptic spines in the hippocampus

Owen J L Rackham, Krasimira Tsaneva-Atanasova, Ayalvadi Ganesh, Jack R. Mellor*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

16 Citations (Scopus)

Abstract

Associative synaptic plasticity is synapse specific and requires coincident activity in pre-synaptic and post-synaptic neurons to activate NMDA receptors (NMDARs). The resultant Ca 2+ influx is the critical trigger for the induction of synaptic plasticity. Given its centrality for the induction of synaptic plasticity, a model for NMDAR activation incorporating the timing of pre-synaptic glutamate release and post-synaptic depolarization by back-propagating action potentials could potentially predict the pre- and post-synaptic spike patterns required to induce synaptic plasticity. We have developed such a model by incorporating currently available data on the timecourse and amplitude of the post-synaptic membrane potential within individual spines. We couple this with data on the kinetics of synaptic NMDARs and then use the model to predict the continuous spine [Ca 2+] in response to regular or irregular pre- and post-synaptic spike patterns. We then incorporate experimental data from synaptic plasticity induction protocols by regular activity patterns to couple the predicted local peak [Ca 2+] to changes in synaptic strength. We find that our model accurately describes [Ca 2+] in dendritic spines resulting from NMDAR activation during pre-synaptic and post-synaptic activity when compared to previous experimental observations. The model also replicates the experimentally determined plasticity outcome of regular and irregular spike patterns when applied to a single synapse. This model could therefore be used to predict the induction of synaptic plasticity under a variety of experimental conditions and spike patterns.

Original languageEnglish
Article numberArticle 31
JournalFrontiers in Synaptic Neuroscience
Issue numberJUL
DOIs
Publication statusPublished - 1 Dec 2010

Keywords

  • Dendritic spines
  • Hippocampus
  • NMDA receptor
  • Spike timing-dependent plasticity
  • Synaptic plasticity

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