Control of synaptic strength and timing by the release-site Ca2+ signal

Abstract

Transmitter release is triggered by highly localized, transient increases in the presynaptic Ca(2+) concentration ([Ca(2+)]). Rapidly decaying [Ca(2+)] elevations were generated using Ca(2+) uncaging techniques, and [Ca(2+)] was measured with a low-affinity Ca(2+) indicator in a giant presynaptic terminal, the calyx of Held, in rat brain slices. The rise time and amplitude of evoked excitatory postsynaptic currents (EPSCs) depended on the half-width of the fluorescence transient, which was predicted by a five-binding site model of a Ca(2+) sensor having relatively high affinity (K(d) approximately 13 microM). Very fast [Ca(2+)] transients (half-width <0.5 ms) evoked EPSCs similar to those elicited by a single action potential (AP) in the same synapse. Triggering release with dual [Ca(2+)] transients of variable amplitudes demonstrated the supralinear transfer function of the sensor. The sensitivity of release to the time course of the [Ca(2+)] transient may contribute to mechanisms by which the presynaptic AP waveform controls synaptic strength.

Ca2+from One or Two Channels Controls Fusion of a Single Vesicle at the Frog Neuromuscular Junction

“…Several models have been suggested for the Ca 2ϩ -dependent steps of release (Shahrezaei and Delaney, 2005). Here we use a high-affinity fast kinetic model suggested by Ca 2ϩ -uncaging experiments performed on the calyx of Held (Bollmann et al, 2000;Bollmann and Sakmann, 2005). We show that our results are robust against changes in the parameters of the release model.…”

“…It is known that the size of the Ca 2ϩ transient at the release site can affect the synaptic delay (Bollmann et al, 2000;Schneggenburger and Neher, 2000;Bollmann and Sakmann, 2005). In our simulation we define the average time of fusion events as the delay of release.…”

Molecular mechanisms that control initiation and termination of physiological depolarization-evoked transmitter release

“…Surprisingly, the time course of physiological release was found to be independent of Ca 2ϩ level and kinetics (37)(38)(39) [in contrast to Ca 2ϩ -uncaging-induced release (2,40), where release kinetics heavily depends on Ca 2ϩ level], suggesting that another factor, somewhat slower in its effect than Ca 2ϩ entry, limits triggering of depolarization-evoked release. In several studies we have shown that this factor is a presynaptic GPCR, whose agonistbinding affinity is voltage-dependent (6-8).…”

Patch pipettes are more useful than initially thought: simultaneous pre- and postsynaptic recording from mammalian CNS synapses in vitro and in vivo

“…2e) Fig. 2d; [2]). This measurement is in reasonable agreement with the initial back-calculated time course (Fig.…”

“…As the spatial relationship between the vesicle release sites, the Ca 2+ entry sites, and the endogenous Ca 2+ buffers is uncertain, the [Ca 2+ ] i dynamics at the site of the Ca 2+ sensor were also unknown. We established recording conditions [4] that allowed us, eventually [2], to determine the time course and amplitude of the local [Ca 2+ ] i transient during an AP in the close vicinity of a vesicular release site (Fig. 2e) Fig.…”