Hippocampal mossy fiber activity evokes Ca2+ release in CA3 pyramidal neurons via a metabotropic glutamate receptor pathway

Neuroscience. 2001;107(1):59-69. doi: 10.1016/s0306-4522(01)00293-7.


Mossy fiber activity can evoke Ca2+ release from internal stores in CA3 neurons, but the physiological conditions under which this occurs and the mechanisms underlying the release are not understood. Using rat hippocampal slices we report here that short trains of mossy fiber stimulation activate group I metabotropic glutamate receptors (mGluRs) on CA3 pyramidal neurons and elicit waves of Ca2+ release from inositol 1,4,5-trisphosphate (IP3) sensitive internal stores that propagate from stratum lucidum to the soma and in some cases distally out the dendrites. Activation of mGluR1,5 receptors by an agonist trans-azetidine-2,4-dicarboxylic acid (tADA) applied to stratum lucidum was also sufficient to induce waves of Ca2+ release. This release was blocked by internal heparin, but not by dantrolene, suggesting the involvement of IP3 rather than ryanodine receptors in not only the initial release but also in the maintenance of the propagating waves. Release could be facilitated by Ca2+ influx through voltage-gated Ca2+ channels, which is consistent with the known Ca2+ sensitivity of IP3 receptors.These results provide insight into the mechanisms and conditions of Ca2+ release in CA3 neurons and demonstrate the powerful influence mossy fiber input can have on these neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Calcium / metabolism
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Dantrolene / pharmacology
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Dendrites / ultrastructure
  • Electric Stimulation
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Heparin / pharmacology
  • Inositol 1,4,5-Trisphosphate Receptors
  • Intracellular Fluid / drug effects
  • Intracellular Fluid / metabolism
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / metabolism*
  • Mossy Fibers, Hippocampal / ultrastructure
  • Muscle Relaxants, Central / pharmacology
  • Narcotic Antagonists / pharmacology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / metabolism*
  • Ryanodine Receptor Calcium Release Channel / drug effects
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Synaptic Transmission / physiology*


  • Calcium Channels
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Inositol 1,4,5-Trisphosphate Receptors
  • Muscle Relaxants, Central
  • Narcotic Antagonists
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Metabotropic Glutamate
  • Ryanodine Receptor Calcium Release Channel
  • Heparin
  • Dantrolene
  • Calcium