Ca2+-Dependent Enhancement of Release by Subthreshold Somatic Depolarization

In many neurons, subthreshold somatic depolarization can spread electrotonically into the axon and modulate subsequent spike-evoked transmission. Although release probability is regulated by intracellular Ca2+, the Ca2+ dependence of this modulatory mechanism has been debated. Using paired recordings from synaptically connected molecular layer interneurons (MLIs) of the rat cerebellum, we observed Ca2+-mediated strengthening of release following brief subthreshold depolarization of the soma. Two-photon microscopy revealed that, at the axon, somatic depolarization evoked Ca2+ influx through voltage-sensitive Ca2+ channels and facilitated spike-evoked Ca2+ entry. Exogenous Ca2+ buffering diminished these Ca2+ transients and eliminated the strengthening of release. Axonal Ca2+ entry elicited by subthreshold somatic depolarization also triggered asynchronous transmission that may deplete vesicle availability and thereby temper release strengthening. In this cerebellar circuit, activity-dependent presynaptic plasticity depends on Ca2+ elevations resulting from both sub- and suprathreshold electrical activity initiated at the soma.

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