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Sci Adv. 2018 Jul 4;4(7):eaat1357. doi: 10.1126/sciadv.aat1357. eCollection 2018 Jul.

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

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Institute of Higher Nervous Activity and Neurophysiology, Moscow 117485, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
Pirogov Russian National Research Medical University, Moscow 117997, Russia.
Institute for Cardiovascular Physiology, Georg August University Göttingen, D-37075 Göttingen, Germany.
Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.


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.

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