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

作者：Roshchin Matvey V; Matlashov Mikhail E; Lerusalimsky Victor N; Balaban Pavel M; Belousov Vsevolod V; Kemenes Gyorgy; Staras Kevin^*; Nikitin Evgeny S^*

来源：Science Advances, 2018, 4(7): eaat1357.

DOI：10.1126/sciadv.aat1357

Action potential shape is a major determinant of synaptic transmission, and mechanisms of spike tuning are therefore of key functional significance. 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 uses the activity history of a bouton or adjacent axonal site to dynamically tune ongoing signaling properties.

• 出版日期2018-7