Analog modulation of spike‐evoked transmission in CA3 circuits is determined by axonal Kv1.1 channels in a time‐dependent manner

Abstract Synaptic transmission usually depends on action potentials (APs) in an all‐or‐none (digital) fashion. Recent studies indicate, however, that subthreshold presynaptic depolarization may facilitate spike‐evoked transmission, thus creating an analog modulation of spike‐evoked synaptic transmission, also called analog–digital (AD) synaptic facilitation. Yet, the underlying mechanisms behind this facilitation remain unclear. We show here that AD facilitation at rat CA3–CA3 synapses is time‐dependent and requires long presynaptic depolarization (5–10 s) for its induction. This depolarization‐induced AD facilitation (d‐ADF) is blocked by the specific Kv1.1 channel blocker dendrotoxin‐K. Using fast voltage‐imaging of the axon, we show that somatic depolarization used for induction of d‐ADF broadened the AP in the axon through inactivation of Kv1.1 channels. Somatic depolarization enhanced spike‐evoked calcium signals in presynaptic terminals, but not basal calcium. In conclusion, axonal Kv1.1 channels determine glutamate release in CA3 neurons in a time‐dependent manner through the control of the presynaptic spike waveform.