Editorial: Determinants of Synaptic Information Transfer: From Ca2+ Binding Proteins to Ca2+ Signaling Domains

Ca 2+ ions are key regulators of fundamental synaptic processes including transmitter release and the induction of plasticity. They act within complex topographical relationships between the sites of Ca 2+ influx and those sites where the Ca 2+ controlled effector proteins are located. These topographies are dynamically shaped by protein-complexes and the spatio-temporal extent of Ca 2+ elevations within these topographies is controlled by Ca 2+ buffers. Ultimately, these spatio-temporal relationships determine the details of Ca 2+ induced effects. This e-book deals with the significance of localized synaptic calcium signaling. Synaptic information transfer begins with presynaptic transmitter release. Wang and Augustine review the concept of local presynaptic Ca 2+ signaling domains and their functional importance for release, focusing on two giant presynaptic terminals, the squid giant synapse and the calyx of Held. Central concepts that still dominate our view about the significance of presynaptic Ca 2+ domains were originally developed using these two synapses. The authors describe the distinction between nano-and micro-domain topographies and the evidence for a developmental regulation of Ca 2+ domains at several synapses. A synapse that operates with nano-domain influx-release coupling is the parallel-fiber (PF) to Purkinje cell (PC) synapse. These synapses show use-dependent facilitation that surprisingly persists in mutant mice lacking calretinin—the major buffer of PF terminals—which leads to increased release probability. Brachtendorf et al. analyzed mechanisms of facilitation at individual PF-PC synapses of calretinin mutant mice using paired patch-clamp recordings. They suggest that a Ca 2+-driven process that rapidly replenishes releasable vesicles operates more effectively in the absence of calretinin, thereby explaining the persistence of facilitation. How critical the maintenance of calcium homeostasis on synaptic function can be is demonstrated by Orduz et al. In their study, knocking out calbindin, a calcium binding protein (CaBP) related to calretinin, had surprisingly little effect on the amplitude of postysynaptic potentials (PSPs) at PC-to-PC synapses. Their detailed study of presynaptic morphology revealed larger boutons and AZs and a higher number of docked vesicles in the mutants. The authors view these changes as a compensatory mechanism to maintain central characteristics of release in the face of a major perturbation.