title: Extracellular Ca2+ depletion contributes to fast activity-dependent modulation of synaptic transmission in the brain.
abstract: 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.
authors.affiliation: Division of Neurophysiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. afine@nimr.mrc.ac.uk
authors.forename: D A
authors.initials: DA
authors.lastname: Rusakov
authors.forename: A
authors.initials: A
authors.lastname: Fine
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D005110:Extracellular Space / Q000502:physiology; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D005456:Fluorescent Dyes; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D002118:Calcium