Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons
Autor: | Alexis Haddjeri-Hopkins, Marianne Amalric, Jorge Ramírez-Franco, Mónica Tapia, Fabien Tell, Jean-Marc Goaillard, Béatrice Marquèze-Pouey |
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Přispěvatelé: | Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE16-0022,LoGIK,Modulation de l'excitabilité neuronale par LGI1(2017) |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
computational modeling
[SDV]Life Sciences [q-bio] Research Article: Confirmation Action Potentials Mice Transgenic Neuronal Excitability Substantia nigra Inhibitory postsynaptic potential patch clamp Mice 03 medical and health sciences 0302 clinical medicine biophysics Animals Tonic (music) Pars Compacta Ion channel 030304 developmental biology 0303 health sciences Pars compacta Chemistry Dopaminergic Neurons Dopaminergic potassium channels Potassium channel Electrophysiology substantia nigra [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] dopamine Neuroscience 030217 neurology & neurosurgery |
Zdroj: | eNeuro eNeuro, Society for Neuroscience, 2021, 8, pp.ENEURO.0207-21.2021. ⟨10.1523/eneuro.0207-21.2021⟩ eNeuro, 2021, 8, pp.ENEURO.0207-21.2021. ⟨10.1523/eneuro.0207-21.2021⟩ |
ISSN: | 2373-2822 |
Popis: | 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 and a biphasic post-inhibitory response. Several studies in rodents have underlined the central role played by the transient A-type current (IA) in the control of pacemaking activity and post-inhibitory rebound properties, thereby influencing both DA release and the physiological response of SNc neurons to incoming inhibitory inputs. Kv4.3 potassium channels were considered to be fully responsible for IA in these neurons, their density being tightly related to pacemaking frequency. In spite of this crucial electrophysiological role, we show that Kv4.3-/- transgenic mice exhibit minor alterations in locomotion and motor learning, although no compensation by functionally overlapping ion channels is observed in Kv4.3-/- SNc DA neurons. Using antigen retrieval immunohistochemistry, we further demonstrate that Kv4.2 potassium channels are also expressed in SNc DA neurons, even though their contribution to IA appears significant only in a minority of neurons (~5-10%). Using correlative analysis on recorded electrophysiological parameters and multi-compartment modeling, we then demonstrate that, rather than its conductance level, IA gating kinetics (inactivation time constant) appear as the main biophysical property defining post-inhibitory rebound delay and pacemaking frequency. Moreover, we show that the hyperpolarization-activated current (IH) has an opposing and complementary influence on the same firing features, and that the biophysical properties of IA and IH are likely coregulated in mouse SNc DA neurons.SIGNIFICANCE STATEMENTSubstantia nigra pars compacta (SNc) dopaminergic (DA) neurons are characterized by pacemaking activity, a broad action potential and biphasic post-inhibitory response. The A-type transient potassium current (IA) plays a central role in both pacemaking activity and post-inhibitory response. While it was thought so far that Kv4.3 ion channels were fully responsible for IA, using a Kv4.3-/- transgenic mouse and antigen retrieval immunohistochemistry we demonstrate that Kv4.2 channels are also expressed in SNc DA neurons, although their contribution is significant in a minority of neurons only. Using electrophysiological recordings and computational modeling, we then demonstrate that IA gating kinetics and its functional complementarity with the hyperpolarization-activated current are major determinants of both pacemaking activity and post-inhibitory response in SNc DA neurons. |
Databáze: | OpenAIRE |
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