A quantitative measurement of the dependence of short-term synaptic enhancement on presynaptic residual calcium

Abstract

We simultaneously measured presynaptic free calcium ion concentration ([Ca2+]i) and synaptic strength at the crayfish claw opener neuromuscular junction (nmj) under a variety of experimental conditions. Our experiments were designed both to test the hypothesis that elevated [Ca2+]i is necessary and sufficient for the induction of a form of synaptic enhancement that persists for several seconds after tetanic stimulation--augmentation--and to determine the quantitative relationship between elevated [Ca2+]i and this enhancement. Action potential trains increased [Ca2+]i and enhanced transmission. During the decay phase of synaptic enhancement known as augmentation (time constant of decay approximately 7 sec at 20 degrees C with < 200 microM fura-2 in terminals), [Ca2+]i was elevated 700 nM or less above rest and an essentially linear relationship between [Ca2+]i and enhancement was observed. Introduction of exogenous Ca2+ buffers into the presynaptic terminal slowed the buildup and recovery kinetics of both [Ca2+]i and the component of synaptic enhancement corresponding to augmentation. The slope of the relationship relating delta [Ca2+]i to augmentation was not changed. The time course of augmentation and recovery of [Ca2+]i remained correlated as the temperature of the preparation was changed from about 10 degrees C to 20 degrees C, but the quantitative relationship of enhancement to [Ca2+]i was increased more than two- to threefold. During moderate frequency trains of action potentials, a slowly developing component of the total synaptic enhancement was approximately linearly related to residual [Ca2+]i measured with fura-2. The quantitative relationship between [Ca2+]i and this component of synaptic enhancement during trains was the same as that during synaptic augmentation after trains.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-Term Presynaptic Plasticity

“…At synapses including the crayfish neuromuscular junction and the calyx of Held synapse, following tetanic stimulation there is a buildup of Ca res that returns to resting levels with a time course that is similar to that of PTP (Delaney et al 1989;Delaney and Tank 1994;Brain and Bennett 1997;Habets and Borst 2005;Korogod et al 2007). The linear correlation between EPSC amplitude and Ca res is compatible with a mechanism in which an increase in Ca res of several hundred nanomolar leads to a doubling of synaptic strength.…”

“…This phenomenon was first described at the neuromuscular junction (del Castillo and Katz 1954) and has subsequently been seen at many other synapses (Magleby 1987;Delaney and Tank 1994;Eliot et al 1994;Habets and Borst 2005;Korogod et al 2005Korogod et al , 2007He et al 2009). The observations that the elevations in the frequency of spontaneous events and PTP have similar time courses in some cases, and that both are a consequence of increases in nerve terminal calcium, have prompted speculation that a common mechanism might produce both phenomena (Magleby 1987).…”

Limit on the Role of Activity in Controlling the Release-Ready Supply of Synaptic Vesicles

“…That would happen if each individual action potential triggered the exocytosis of waiting release-ready vesicles with the same efficiency during the fourth second of 20 Hz stimulation as they do when the stimulus frequency is switched instead to 40 Hz. We stress that during the first second or two of stimulation, the efficiency with which action potentials elicit exocytosis is known to increase substantially within presynaptic terminals (Stevens and Wesseling, 1999a) in a manner that depends on the stimulation frequency (Zengel and Magleby, 1982;Zucker, 1989;Delaney and Tank, 1994). Because of this frequency facilitation, ␤ might be expected to more than double when the stimulus frequency is doubled in these experiments, and our estimate of the settling time course should thus be considered an upper bound estimate; that is, Equation 1 would also be consistent with a faster time course of decay.…”

Augmentation Increases Vesicular Release Probability in the Presence of Masking Depression at the Frog Neuromuscular Junction

“…Because augmentation is associated with and requires an increase in free Ca 2ϩ in nerve terminals under conditions where augmentation is obviously present (Swandulla et al, 1991;Delaney and Tank, 1994;Kamiya and Zucker, 1994;Regehr et al, 1994;Rosenmund et al, 2002;Zucker and Regehr, 2002), we examined whether there is a component of free Ca 2ϩ in the nerve terminal with a time course similar to augmentation under conditions like those in Figure 2 where depression would mask augmentation. Ratiometric imaging was used to estimate changes in residual Ca 2ϩ in synaptic terminals of the frog NMJ during conditioning-testing trials after the terminals were loaded with fura-2 by backfilling (see Materials and Methods).…”