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A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms

The neurons of the deep cerebellar nuclei (DCNn) represent the main functional link between the cerebellar cortex and the rest of the central nervous system. Therefore, understanding the electrophysiological properties of DCNn is of fundamental importance to understand the overall functioning of the...

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Autores principales: Berry, Hugues, Genet, Stéphane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017079/
https://www.ncbi.nlm.nih.gov/pubmed/33796951
http://dx.doi.org/10.1186/s13408-021-00105-3
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author Berry, Hugues
Genet, Stéphane
author_facet Berry, Hugues
Genet, Stéphane
author_sort Berry, Hugues
collection PubMed
description The neurons of the deep cerebellar nuclei (DCNn) represent the main functional link between the cerebellar cortex and the rest of the central nervous system. Therefore, understanding the electrophysiological properties of DCNn is of fundamental importance to understand the overall functioning of the cerebellum. Experimental data suggest that DCNn can reversibly switch between two states: the firing of spikes (F state) and a stable depolarized state (SD state). We introduce a new biophysical model of the DCNn membrane electro-responsiveness to investigate how the interplay between the documented conductances identified in DCNn give rise to these states. In the model, the F state emerges as an isola of limit cycles, i.e. a closed loop of periodic solutions disconnected from the branch of SD fixed points. This bifurcation structure endows the model with the ability to reproduce the [Formula: see text] transition triggered by hyperpolarizing current pulses. The model also reproduces the [Formula: see text] transition induced by blocking Ca currents and ascribes this transition to the blocking of the high-threshold Ca current. The model suggests that intracellular current injections can trigger fully reversible [Formula: see text] transitions. Investigation of low-dimension reduced models suggests that the voltage-dependent Na current is prominent for these dynamical features. Finally, simulations of the model suggest that physiological synaptic inputs may trigger [Formula: see text] transitions. These transitions could explain the puzzling observation of positively correlated activities of connected Purkinje cells and DCNn despite the former inhibit the latter.
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spelling pubmed-80170792021-04-16 A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms Berry, Hugues Genet, Stéphane J Math Neurosci Research The neurons of the deep cerebellar nuclei (DCNn) represent the main functional link between the cerebellar cortex and the rest of the central nervous system. Therefore, understanding the electrophysiological properties of DCNn is of fundamental importance to understand the overall functioning of the cerebellum. Experimental data suggest that DCNn can reversibly switch between two states: the firing of spikes (F state) and a stable depolarized state (SD state). We introduce a new biophysical model of the DCNn membrane electro-responsiveness to investigate how the interplay between the documented conductances identified in DCNn give rise to these states. In the model, the F state emerges as an isola of limit cycles, i.e. a closed loop of periodic solutions disconnected from the branch of SD fixed points. This bifurcation structure endows the model with the ability to reproduce the [Formula: see text] transition triggered by hyperpolarizing current pulses. The model also reproduces the [Formula: see text] transition induced by blocking Ca currents and ascribes this transition to the blocking of the high-threshold Ca current. The model suggests that intracellular current injections can trigger fully reversible [Formula: see text] transitions. Investigation of low-dimension reduced models suggests that the voltage-dependent Na current is prominent for these dynamical features. Finally, simulations of the model suggest that physiological synaptic inputs may trigger [Formula: see text] transitions. These transitions could explain the puzzling observation of positively correlated activities of connected Purkinje cells and DCNn despite the former inhibit the latter. Springer Berlin Heidelberg 2021-04-01 /pmc/articles/PMC8017079/ /pubmed/33796951 http://dx.doi.org/10.1186/s13408-021-00105-3 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research
Berry, Hugues
Genet, Stéphane
A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms
title A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms
title_full A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms
title_fullStr A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms
title_full_unstemmed A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms
title_short A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms
title_sort model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017079/
https://www.ncbi.nlm.nih.gov/pubmed/33796951
http://dx.doi.org/10.1186/s13408-021-00105-3
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