IP(3) mobilization and diffusion determine the timing window of Ca(2+) release by synaptic stimulation and a spike in rat CA1 pyramidal cells

Hippocampus. 2010 Apr;20(4):524-39. doi: 10.1002/hipo.20644.


Synaptically activated calcium release from internal stores in CA1 pyramidal neurons is generated via metabotropic glutamate receptors by mobilizing IP(3). Ca(2+) release spreads as a large amplitude wave in a restricted region of the apical dendrites of these cells. These Ca(2+) waves have been shown to induce certain forms of synaptic potentiation and have been hypothesized to affect other forms of plasticity. Pairing a single backpropagating action potential (bAP) with repetitive synaptic stimulation evokes Ca(2+) release when synaptic stimulation alone is subthreshold for generating release. We examined the timing window for this synergistic effect under conditions favoring Ca(2+) release. The window, measured from the end of the train, lasted 250-500 ms depending on the duration of stimulation tetanus. The window appears to correspond to the time when both IP(3) concentration and [Ca(2+)](i) are elevated at the site of the IP(3) receptor. Detailed analysis of the mechanisms determining the duration of the window, including experiments using different forms of caged IP(3) instead of synaptic stimulation, suggest that the most significant processes are the time for IP(3) to diffuse away from the site of generation and the time course of IP(3) production initiated by activation of mGluRs. IP(3) breakdown, desensitization of the IP(3) receptor, and the kinetics of IP(3) unbinding from the receptor may affect the duration of the window but are less significant. The timing window is short but does not appear to be short enough to suggest that this form of coincidence detection contributes to conventional spike timing-dependent synaptic plasticity in these cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology
  • Animals
  • CA1 Region, Hippocampal / physiology*
  • Calcium / metabolism*
  • Dendrites / physiology
  • Electric Stimulation
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Patch-Clamp Techniques
  • Pyramidal Cells / physiology*
  • Rats
  • Receptors, Metabotropic Glutamate / physiology
  • Synapses / physiology
  • Synaptic Transmission / physiology*
  • Time Factors


  • Inositol 1,4,5-Trisphosphate Receptors
  • Receptors, Metabotropic Glutamate
  • Inositol 1,4,5-Trisphosphate
  • Calcium