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Prefrontal - subthalamic pathway supports action selection in a spatial working memory task

Subthalamic nucleus (STN) is the main source of feed-forward excitation in the basal ganglia and a main target of therapeutic deep brain stimulation in movement disorders. Alleviation of motor symptoms during STN stimulation can be accompanied by deterioration of abilities to quickly choose between...

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Autores principales: Heikenfeld, Carla, Mederos, Sara, Chen, Changwan, Korotkova, Tatiana, Schnitzler, Alfons, Ponomarenko, Alexey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320162/
https://www.ncbi.nlm.nih.gov/pubmed/32591609
http://dx.doi.org/10.1038/s41598-020-67185-1
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author Heikenfeld, Carla
Mederos, Sara
Chen, Changwan
Korotkova, Tatiana
Schnitzler, Alfons
Ponomarenko, Alexey
author_facet Heikenfeld, Carla
Mederos, Sara
Chen, Changwan
Korotkova, Tatiana
Schnitzler, Alfons
Ponomarenko, Alexey
author_sort Heikenfeld, Carla
collection PubMed
description Subthalamic nucleus (STN) is the main source of feed-forward excitation in the basal ganglia and a main target of therapeutic deep brain stimulation in movement disorders. Alleviation of motor symptoms during STN stimulation can be accompanied by deterioration of abilities to quickly choose between conflicting alternatives. Cortical afferents to the subthalamic region (ST), comprising STN and zona incerta (ZI), include projections from the medial prefrontal cortex (mPFC), yet little is known about prefrontal-subthalamic coordination and its relevance for decision-making. Here we combined electrophysiological recordings with optogenetic manipulations of projections from mPFC to ST in mice as they performed a spatial working memory task (T-maze) or explored an elevated plus maze (anxiety test). We found that gamma oscillations (30–70 Hz) are coordinated between mPFC and ST at theta (5–10 Hz) and, less efficiently, at sub-theta (2–5 Hz) frequencies. An optogenetic detuning of the theta/gamma cross-frequency coupling between the regions into sub-theta range impaired performance in the T-maze, yet did not affect anxiety-related behaviors in the elevated plus maze. Both detuning and inhibition of the mPFC-ST pathway led to repeated incorrect choices in the T-maze. These effects were not associated with changes of anxiety and motor activity measures. Our findings suggest that action selection in a cognitively demanding task crucially involves theta rhythmic coordination of gamma oscillatory signaling in the prefrontal-subthalamic pathway.
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spelling pubmed-73201622020-06-30 Prefrontal - subthalamic pathway supports action selection in a spatial working memory task Heikenfeld, Carla Mederos, Sara Chen, Changwan Korotkova, Tatiana Schnitzler, Alfons Ponomarenko, Alexey Sci Rep Article Subthalamic nucleus (STN) is the main source of feed-forward excitation in the basal ganglia and a main target of therapeutic deep brain stimulation in movement disorders. Alleviation of motor symptoms during STN stimulation can be accompanied by deterioration of abilities to quickly choose between conflicting alternatives. Cortical afferents to the subthalamic region (ST), comprising STN and zona incerta (ZI), include projections from the medial prefrontal cortex (mPFC), yet little is known about prefrontal-subthalamic coordination and its relevance for decision-making. Here we combined electrophysiological recordings with optogenetic manipulations of projections from mPFC to ST in mice as they performed a spatial working memory task (T-maze) or explored an elevated plus maze (anxiety test). We found that gamma oscillations (30–70 Hz) are coordinated between mPFC and ST at theta (5–10 Hz) and, less efficiently, at sub-theta (2–5 Hz) frequencies. An optogenetic detuning of the theta/gamma cross-frequency coupling between the regions into sub-theta range impaired performance in the T-maze, yet did not affect anxiety-related behaviors in the elevated plus maze. Both detuning and inhibition of the mPFC-ST pathway led to repeated incorrect choices in the T-maze. These effects were not associated with changes of anxiety and motor activity measures. Our findings suggest that action selection in a cognitively demanding task crucially involves theta rhythmic coordination of gamma oscillatory signaling in the prefrontal-subthalamic pathway. Nature Publishing Group UK 2020-06-26 /pmc/articles/PMC7320162/ /pubmed/32591609 http://dx.doi.org/10.1038/s41598-020-67185-1 Text en © The Author(s) 2020 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Heikenfeld, Carla
Mederos, Sara
Chen, Changwan
Korotkova, Tatiana
Schnitzler, Alfons
Ponomarenko, Alexey
Prefrontal - subthalamic pathway supports action selection in a spatial working memory task
title Prefrontal - subthalamic pathway supports action selection in a spatial working memory task
title_full Prefrontal - subthalamic pathway supports action selection in a spatial working memory task
title_fullStr Prefrontal - subthalamic pathway supports action selection in a spatial working memory task
title_full_unstemmed Prefrontal - subthalamic pathway supports action selection in a spatial working memory task
title_short Prefrontal - subthalamic pathway supports action selection in a spatial working memory task
title_sort prefrontal - subthalamic pathway supports action selection in a spatial working memory task
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320162/
https://www.ncbi.nlm.nih.gov/pubmed/32591609
http://dx.doi.org/10.1038/s41598-020-67185-1
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