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Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons

Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons display a peculiar electrical phenotype characterized in vitro by a spontaneous tonic regular activity (pacemaking activity), a broad action potential (AP) and a biphasic postinhibitory response. The transient A-type current (I(A)) is kn...

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Autores principales: Haddjeri-Hopkins, Alexis, Tapia, Mónica, Ramirez-Franco, Jorge, Tell, Fabien, Marqueze-Pouey, Béatrice, Amalric, Marianne, Goaillard, Jean-Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293280/
https://www.ncbi.nlm.nih.gov/pubmed/34131060
http://dx.doi.org/10.1523/ENEURO.0207-21.2021
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author Haddjeri-Hopkins, Alexis
Tapia, Mónica
Ramirez-Franco, Jorge
Tell, Fabien
Marqueze-Pouey, Béatrice
Amalric, Marianne
Goaillard, Jean-Marc
author_facet Haddjeri-Hopkins, Alexis
Tapia, Mónica
Ramirez-Franco, Jorge
Tell, Fabien
Marqueze-Pouey, Béatrice
Amalric, Marianne
Goaillard, Jean-Marc
author_sort Haddjeri-Hopkins, Alexis
collection PubMed
description Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons display a peculiar electrical phenotype characterized in vitro by a spontaneous tonic regular activity (pacemaking activity), a broad action potential (AP) and a biphasic postinhibitory response. The transient A-type current (I(A)) is known to play a crucial role in this electrical phenotype, and so far, this current was considered to be carried exclusively by Kv4.3 potassium channels. Using Kv4.3−/− transgenic mice, we demonstrate that the constitutive loss of this channel is associated with increased exploratory behavior and impaired motor learning at the behavioral level. Consistently, it is also associated with a lack of compensatory changes in other ion currents at the cellular level. Using antigen retrieval (AR) immunohistochemistry, we then demonstrate that Kv4.2 potassium channels are also expressed in SNc DA neurons, although their contribution to I(A) appears significant only in a minority of neurons (∼5–10%). Using correlative analysis on recorded electrophysiological parameters and multicompartment modeling, we then demonstrate that, rather than its conductance level, I(A) gating kinetics (inactivation time constant) appear as the main biophysical property defining postinhibitory rebound delay and pacemaking frequency. Moreover, we show that the hyperpolarization-activated current (I(H)) has an opposing and complementary influence on the same firing features.
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spelling pubmed-82932802021-07-21 Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons Haddjeri-Hopkins, Alexis Tapia, Mónica Ramirez-Franco, Jorge Tell, Fabien Marqueze-Pouey, Béatrice Amalric, Marianne Goaillard, Jean-Marc eNeuro Research Article: Confirmation Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons display a peculiar electrical phenotype characterized in vitro by a spontaneous tonic regular activity (pacemaking activity), a broad action potential (AP) and a biphasic postinhibitory response. The transient A-type current (I(A)) is known to play a crucial role in this electrical phenotype, and so far, this current was considered to be carried exclusively by Kv4.3 potassium channels. Using Kv4.3−/− transgenic mice, we demonstrate that the constitutive loss of this channel is associated with increased exploratory behavior and impaired motor learning at the behavioral level. Consistently, it is also associated with a lack of compensatory changes in other ion currents at the cellular level. Using antigen retrieval (AR) immunohistochemistry, we then demonstrate that Kv4.2 potassium channels are also expressed in SNc DA neurons, although their contribution to I(A) appears significant only in a minority of neurons (∼5–10%). Using correlative analysis on recorded electrophysiological parameters and multicompartment modeling, we then demonstrate that, rather than its conductance level, I(A) gating kinetics (inactivation time constant) appear as the main biophysical property defining postinhibitory rebound delay and pacemaking frequency. Moreover, we show that the hyperpolarization-activated current (I(H)) has an opposing and complementary influence on the same firing features. Society for Neuroscience 2021-07-20 /pmc/articles/PMC8293280/ /pubmed/34131060 http://dx.doi.org/10.1523/ENEURO.0207-21.2021 Text en Copyright © 2021 Haddjeri-Hopkins et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article: Confirmation
Haddjeri-Hopkins, Alexis
Tapia, Mónica
Ramirez-Franco, Jorge
Tell, Fabien
Marqueze-Pouey, Béatrice
Amalric, Marianne
Goaillard, Jean-Marc
Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons
title Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons
title_full Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons
title_fullStr Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons
title_full_unstemmed Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons
title_short Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons
title_sort refining the identity and role of kv4 channels in mouse substantia nigra dopaminergic neurons
topic Research Article: Confirmation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293280/
https://www.ncbi.nlm.nih.gov/pubmed/34131060
http://dx.doi.org/10.1523/ENEURO.0207-21.2021
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