Unifying Long-Term Plasticity Rules for Excitatory Synapses by Modeling Dendrites of Cortical Pyramidal Neurons

Cell Rep. 2019 Dec 24;29(13):4295-4307.e6. doi: 10.1016/j.celrep.2019.11.068.


A large number of experiments have indicated that precise spike times, firing rates, and synapse locations crucially determine the dynamics of long-term plasticity induction in excitatory synapses. However, it remains unknown how plasticity mechanisms of synapses distributed along dendritic trees cooperate to produce the wide spectrum of outcomes for various plasticity protocols. Here, we propose a four-pathway plasticity framework that is well grounded in experimental evidence and apply it to a biophysically realistic cortical pyramidal neuron model. We show in computer simulations that several seemingly contradictory experimental landmark studies are consistent with one unifying set of mechanisms when considering the effects of signal propagation in dendritic trees with respect to synapse location. Our model identifies specific spatiotemporal contributions of dendritic and axo-somatic spikes as well as of subthreshold activation of synaptic clusters, providing a unified parsimonious explanation not only for rate and timing dependence but also for location dependence of synaptic changes.

Keywords: NMDA spikes; compartmental modeling; dendritic spikes; long term depression (LTD); long term potentiation (LTP); spike timing dependent plasticity (STDP); synaptic cooperativity; synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology*
  • Computer Simulation
  • Dendrites / metabolism*
  • Dendrites / ultrastructure
  • Gene Expression
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Long-Term Potentiation / physiology*
  • Models, Neurological*
  • Patch-Clamp Techniques
  • Pyramidal Cells / metabolism*
  • Pyramidal Cells / ultrastructure
  • Rats
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Synaptic Transmission / physiology


  • Receptor, Cannabinoid, CB1
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1