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YEAR : 2021

Endocannabinoids tune intrinsic excitability in O-LM interneurons by direct modulation of post-synaptic Kv7 channels

AUTHORS : Incontro S, Sammari M, Azzaz F, Inglebert Y, Ankri N, Russier M, Fantini J, Debanne D.

JOURNAL : Journal of Neuroscience
KCNQ-Kv7 channels are found at the axon initial segment of pyramidal neurons where they control cell firing and membrane potential. In oriens lacunosum moleculare (O-LM) interneurons, these channels are mainly expressed in the dendrites, suggesting a peculiar function of Kv7 channels in these neurons. Here, we show that Kv7 channel activity is up-regulated following induction of presynaptic long-term synaptic depression (LTD) in O-LM interneurons from rats of both sex, thus resulting in a synergistic long-term depression of intrinsic neuronal excitability (LTD-IE). Both LTD and LTD-IE involve endocannabinoid (eCB) biosynthesis for their induction. However, while LTD is dependent on CB1 receptors LTD-IE is not. Molecular modeling shows strong interaction of eCBs with Kv7.2/3 channel, suggesting a persistent action of these lipids on Kv7 channel activity. Our data thus unveil a major role for eCB synthesis in triggering both synaptic and intrinsic depression in O-LM interneurons.