title: The role of presynaptic calcium in short-term enhancement at the hippocampal mossy fiber synapse.
abstract: The mossy fiber synapse between dentate granule cells and CA3 pyramidal cells in the guinea pig hippocampus shows a robust short-term synaptic enhancement. We have simultaneously measured presynaptic residual free calcium ([Ca2+]i) and postsynaptic field potentials at this synapse to examine the role of [Ca2+]i in this enhancement. Single action potentials produced an increase in [Ca2+]i of 10-50 nM that decayed to resting levels with a time constant of about 1 sec. Trains of action potentials produced larger [Ca2+]i increases that returned more slowly to resting levels. Following the onset of moderate frequency stimulus trains (0.1-5 Hz), synaptic transmission and [Ca2+]i both increased and eventually plateaued. During the steady-state phase a linear relationship between [Ca2+]i and synaptic enhancement was observed. During the initial buildup, however, [Ca2+]i rose more rapidly than synaptic enhancement. Similarly, during the decay phase immediately following termination of a stimulus train, [Ca2+]i returned to prestimulus levels faster than synaptic enhancement. High concentrations of the calcium buffer EGTA in the presynaptic terminal slowed the buildup and decay of both [Ca2+]i and synaptic enhancement produced by stimulus trains. Under these conditions, the time course of [Ca2+]i and synaptic enhancement were well matched. This suggests that, despite the differences in kinetic rates observed for normal buffering conditions, increases in [Ca2+]i play a causal role in short-term enhancement. An increase in [Ca2+]i of 10-30 nM produced a twofold enhancement. We propose a simple kinetic model to explain these results. The model assumes that synaptic enhancement is controlled by a Ca-dependent first-order reaction. According to this scheme, a change in [Ca2+]i alters neurotransmitter release, but the slow kinetics of the underlying reaction introduces a temporal filter, producing a delay in the change in synaptic enhancement.
authors.affiliation: AT&T Bell Laboratories, Murray Hill, New Jersey 07974.
authors.forename: W G
authors.initials: WG
authors.lastname: Regehr
authors.forename: K R
authors.initials: KR
authors.lastname: Delaney
authors.forename: D W
authors.initials: DW
authors.lastname: Tank
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008433:Mathematics; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013696:Temperature; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes; C049925:fura-2-am; D004533:Egtazic Acid; D004492:Edetic Acid; D002118:Calcium; D016257:Fura-2