Analogue signaling of somatodendritic synaptic activity to axon enhances GABA release in young cerebellar molecular...

Axons are equipped with the digital signaling capacity by which they generate and faithfully propagate action potentials (APs), and also with the analogue signaling capacity by which subthreshold activity in dendrites and soma is transmitted down the axon. Despite intense work, the extent and physiological role for subthreshold synaptic activity reaching the presynaptic boutons has remained elusive because of the technical limitation to record from them. To address this issue, we made simultaneous patch-clamp recordings from the presynaptic varicosities of cerebellar GABAergic interneurons together with their parent soma or postsynaptic target cells in young rat slices and/or primary cultures. Our tour-de-force direct functional dissection indicates that the somatodendritic spontaneous excitatory synaptic potentials are transmitted down the axon for significant distances, depolarizing presynaptic boutons. These analogously transmitted excitatory synaptic potentials augment presynaptic Ca⁺⁺ influx upon arrival of an immediately following AP through a mechanism that involves a voltage-dependent priming of the Ca⁺⁺ channels, leading to an increase in GABA release, without any modification in the presynaptic AP waveform or residual Ca⁺⁺. Our work highlights the role of the axon in synaptic integration.