Extracellular Ca2+ depletion contributes to fast activity-dependent modulation of synaptic transmission in the brain

Neuron. 2003 Jan 23;37(2):287-97. doi: 10.1016/s0896-6273(03)00025-4.


Synaptic activation is associated with rapid changes in intracellular Ca(2+), while the extracellular Ca(2+) level is generally assumed to be constant. Here, using a novel optical method to measure changes in extracellular Ca(2+) at high spatial and temporal resolution, we find that brief trains of synaptic transmission in hippocampal area CA1 induce transient depletion of extracellular Ca(2+). We show that this depletion, which depends on postsynaptic NMDA receptor activation, decreases the Ca(2+) available to enter individual presynaptic boutons of CA3 pyramidal cells. This in turn reduces the probability of consecutive synaptic releases at CA3-CA1 synapses and therefore contributes to short-term paired-pulse depression of minimal responses. This activity-dependent depletion of extracellular Ca(2+) represents a novel form of fast retrograde synaptic signaling that can modulate glutamatergic information transfer in the brain.

Publication types

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

MeSH terms

  • Animals
  • Brain / physiology*
  • Calcium / physiology*
  • Calcium Signaling / physiology
  • Electric Stimulation
  • Electrophysiology
  • Extracellular Space / physiology
  • Fluorescent Dyes
  • Glutamic Acid / physiology
  • Hippocampus / physiology
  • Immunohistochemistry
  • In Vitro Techniques
  • Male
  • Microscopy, Confocal
  • Neurotransmitter Agents / metabolism
  • Presynaptic Terminals / physiology
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Synaptic Transmission / physiology*


  • Fluorescent Dyes
  • Neurotransmitter Agents
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Calcium