A BK-channel-mediated feedback pathway links single-synapse activity with action potential sharpening in repetitive firing

Action potential shape is a major determinant of synaptic transmission and mechanisms of spike-tuning are therefore of key functional significance. Here we demonstrate that synaptic activity itself modulates future spikes in the same neuron via a rapid feedback pathway. Using Ca2+ imaging and targeted uncaging approaches in layer 5 neocortical pyramidal neurons we show that the single spike-evoked Ca2+ rise occurring in one proximal bouton or first node of Ranvier drives a significant sharpening of subsequent action potentials recorded at the soma. This form of intrinsic modulation, mediated by the activation of large conductance Ca2+/voltage-dependent K+ channels (BK channels), acts to maintain high-frequency firing and limit runaway spike broadening during repetitive firing, preventing an otherwise significant escalation of synaptic transmission. Our findings identify a novel short-term presynaptic plasticity mechanism that utilizes the activity-history of a bouton or adjacent axonal site to dynamically tune ongoing signalling properties.