Endocannabinoids Tune Intrinsic Excitability in O-LM Interneurons by Direct Modulation of Postsynaptic Kv7 Channels

Salvatore Incontro (1) , Malika Sammari (1) , Fodil Azzaz (1) , Yanis Inglebert (1) , Norbert Ankri (1) , Michael Russier (1) , Jacques Fantini (1) , Dominique Debanne (1)

1 UNIS - Inserm U1072 - Unité de Neurobiologie des canaux Ioniques et de la Synapse

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 upregulated 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 excitability (LTD-IE). Both LTD and LTD-IE involve endocannabinoid (eCB) biosynthesis for induction. However, although LTD is dependent on cannabinoid type 1 receptors, LTD-IE is not. Molecular modeling shows a 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.

Mots clés: 2-AG; interneurons; intrinsic plasticity; LTD; M-current; synaptic plasticity Significance Statement S.I. and D.D. designed research

Domaines: Neurobiologie

Salvatore Incontro, Malika Sammari, Fodil Azzaz, Yanis Inglebert, Norbert Ankri, et al.. Endocannabinoids Tune Intrinsic Excitability in O-LM Interneurons by Direct Modulation of Postsynaptic Kv7 Channels. Journal of Neuroscience, 2021, 41, pp.9521 - 9538. ⟨10.1523/jneurosci.1279-21.2021⟩. ⟨hal-03437133⟩