Neuron
Volume 81, Issue 4, 19 February 2014, Pages 787-799
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Article
Membrane Lipids Tune Synaptic Transmission by Direct Modulation of Presynaptic Potassium Channels

https://doi.org/10.1016/j.neuron.2013.12.028Get rights and content
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Highlights

  • Arachidonic acid acts as a retrograde messenger at hippocampal synapses

  • Activity-dependent release of AA potentiates synaptic transmission

  • AA acts by inhibiting presynaptic voltage-gated K+ channels

  • AA-mediated short-term plasticity lowers the threshold for presynaptic LTP

Summary

Voltage-gated potassium (Kv) channels are involved in action potential (AP) repolarization in excitable cells. Exogenous application of membrane-derived lipids, such as arachidonic acid (AA), regulates the gating of Kv channels. Whether membrane-derived lipids released under physiological conditions have an impact on neuronal coding through this mechanism is unknown. We show that AA released in an activity-dependent manner from postsynaptic hippocampal CA3 pyramidal cells acts as retrograde messenger, inducing a robust facilitation of mossy fiber (Mf) synaptic transmission over several minutes. AA acts by broadening presynaptic APs through the direct modulation of Kv channels. This form of short-term plasticity can be triggered when postsynaptic cell fires with physiologically relevant patterns and sets the threshold for the induction of the presynaptic form of long-term potentiation (LTP) at hippocampal Mf synapses. Hence, direct modulation of presynaptic Kv channels by activity-dependent release of lipids serves as a physiological mechanism for tuning synaptic transmission.

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These authors contributed equally to this work