Reliability and Heterogeneity of Calcium Signaling at Single Presynaptic Boutons of Cerebellar Granule Cells

  • Brenowitz S
  • Regehr W
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Activity-dependent elevation of calcium within presynaptic boutons regulates many aspects of synaptic transmission. Here, we examine presynaptic residual calcium (Ca(res)) transients in individual presynaptic boutons of cerebellar granule cells at near-physiological temperatures using two-photon microscopy. Properties of Ca(res) under conditions of zero-added buffer were determined by measuring Ca(res) transients while loading boutons to a steady-state indicator concentration. These experiments revealed that, in the absence of exogenous calcium buffers, a single action potential evokes transients of Ca(res) that vary widely in different boutons both in amplitude (400-900 nM) and time course (25-55 ms). Variation in calcium influx density, endogenous buffer capacity, and calcium extrusion density contribute to differences in Ca(res) among boutons. Heterogeneity in Ca(res) within different boutons suggests that plasticity can be regulated independently at different synapses arising from an individual granule cell. In a given bouton, Ca(res) signals were highly reproducible from trial to trial and failures of calcium influx were not observed. We find that a factor contributing to this reliability is that an action potential opens a large number of calcium channels (20-125) in a bouton. Presynaptic calcium signals were also used to assess the ability of granule cell axons to convey somatically generated action potentials to distant synapses. In response to pairs of action potentials or trains, granule cell boutons showed a remarkable ability to respond reliably at frequencies up to 500 Hz. Thus, individual boutons appear specialized for reliable calcium signaling during bursts of high-frequency activation such as those that are observed in vivo.

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  • S. D. Brenowitz

  • W. G. Regehr

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