Multiscale interactions between chemical and electric signaling in LTP induction, LTP reversal and dendritic excitability

Neural Netw. 2011 Nov;24(9):943-9. doi: 10.1016/j.neunet.2011.05.001. Epub 2011 May 10.


Synaptic plasticity leads to long-term changes in excitability, whereas cellular homeostasis maintains excitability. Both these processes involve interactions between molecular events, electrical events, and network activity. Here I explore these intersections with a multilevel model that embeds molecular events following synaptic calcium influx into a multicompartmental electrical model of a CA1 hippocampal neuron. I model synaptic plasticity using a two-state (bistable) molecular switch that controls glutamate receptor insertion into the post-synaptic density. I also model dendritic activation of the MAPK signaling pathway, which in turn phosphorylates and inactivates A-type potassium channels. I find that LTP-inducing stimuli turn on individual spines and raise dendritic excitability. This increases the amount of calcium that enters due to synaptic input triggered by network activity. As a result, LTD is now induced in some synapses. Overall, this suggests a mechanism for cellular homeostasis where strengthening of some synapses eventually balances out through weakening of a possibly overlapping set of other synapses. Even in this very narrow slice of cellular events, interesting system properties arise at the interface between multiple scales of cellular function.

Publication types

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

MeSH terms

  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / physiology
  • Calcium Signaling / physiology
  • Computer Simulation*
  • Dendrites / physiology*
  • Electrophysiological Phenomena*
  • Long-Term Potentiation / physiology*
  • Mitogen-Activated Protein Kinases / physiology
  • Models, Neurological*
  • Neuronal Plasticity / physiology
  • Neurotransmitter Agents / physiology*
  • Post-Synaptic Density
  • Potassium Channels / physiology
  • Receptors, AMPA / physiology
  • Signal Transduction / physiology*
  • Synapses / enzymology
  • Synapses / physiology


  • Neurotransmitter Agents
  • Potassium Channels
  • Receptors, AMPA
  • Mitogen-Activated Protein Kinases