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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2021

Homeostatic regulation of axonal Kv1.1 channels accounts for both synaptic and intrinsic modifications in the hippocampal CA3 circuit

Mickaël Zbili
Sylvain Rama
  • Fonction : Auteur
Maria-José Benitez
  • Fonction : Auteur
Laure Fronzaroli-Molinieres
  • Fonction : Auteur
Andrzej Bialowas
  • Fonction : Auteur
Norah Boumedine-Guignon
  • Fonction : Auteur
Juan José Garrido
  • Fonction : Auteur

Résumé

Homeostatic plasticity of intrinsic excitability goes hand in hand with homeostatic plasticity of synaptic transmission. However, the mechanisms linking the two forms of homeostatic regulation have not been identified so far. Using electrophysiological, imaging, and immunohistochemical techniques, we show here that blockade of excitatory synaptic receptors for 2 to 3 d induces an up-regulation of both synaptic transmission at CA3–CA3 connections and intrinsic excitability of CA3 pyramidal neurons. Intrinsic plasticity was found to be mediated by a reduction of Kv1.1 channel density at the axon initial segment. In activity-deprived circuits, CA3–CA3 synapses were found to express a high release probability, an insensitivity to dendrotoxin, and a lack of depolarization-induced presynaptic facilitation, indicating a reduction in presynaptic Kv1.1 function. Further support for the down-regulation of axonal Kv1.1 channels in activity-deprived neurons was the broadening of action potentials measured in the axon. We conclude that regulation of the axonal Kv1.1 channel constitutes a major mechanism linking intrinsic excitability and synaptic strength that accounts for the functional synergy existing between homeostatic regulation of intrinsic excitability and synaptic transmission.
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Dates et versions

hal-03439967 , version 1 (15-03-2022)

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Mickaël Zbili, Sylvain Rama, Maria-José Benitez, Laure Fronzaroli-Molinieres, Andrzej Bialowas, et al.. Homeostatic regulation of axonal Kv1.1 channels accounts for both synaptic and intrinsic modifications in the hippocampal CA3 circuit. Proceedings of the National Academy of Sciences of the United States of America, 2021, ⟨10.1073/pnas.2110601118⟩. ⟨hal-03439967⟩
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