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 Ca ²⁺, 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 Ca ²⁺-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.