The actions of synaptically released zinc at hippocampal mossy fiber synapses

Neuron. 2000 Apr;26(1):187-96. doi: 10.1016/s0896-6273(00)81149-6.


Zn2+ is present at high concentrations in the synaptic vesicles of hippocampal mossy fibers. We have used Zn2+ chelators and the mocha mutant mouse to address the physiological role of Zn2+ in this pathway. Zn2+ is not involved in the unique presynaptic plasticities observed at mossy fiber synapses but is coreleased with glutamate from these synapses, both spontaneously and with electrical stimulation, where it exerts a strong modulatory effect on the NMDA receptors. Zn2+ tonically occupies the high-affinity binding site of NMDA receptors at mossy fiber synapses, whereas the lower affinity voltage-dependent Zn2+ binding site is occupied during action potential driven-release. We conclude that Zn2+ is a modulatory neurotransmitter released from mossy fiber synapses and plays an important role in shaping the NMDA receptor response at these synapses.

Publication types

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

MeSH terms

  • Animals
  • Chelating Agents / pharmacology
  • Edetic Acid / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Guinea Pigs
  • Mice
  • Mice, Mutant Strains
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / metabolism*
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Synapses / drug effects
  • Synapses / physiology*
  • Zinc / physiology*


  • Chelating Agents
  • Receptors, N-Methyl-D-Aspartate
  • Edetic Acid
  • Zinc