Dynamic dichotomy of accumbal population activity underlies cocaine sensitization

Locomotor sensitization (LS) is an early behavioral adaptation to addictive drugs, driven by the increase of dopamine in the Nucleus Accumbens (NAc). However, the effect on accumbal population activity remains elusive. Here, we used single-cell calcium imaging in mice to record the activity of dopam...

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Autores principales:	Ruud van Zessen, Yue Li, Lucile Marion-Poll, Nicolas Hulo, Jérôme Flakowski, Christian Lüscher
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	nucleus accumbens dopamine spiny projection neuron cocaine calcium imaging population coding Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3f96f96faee244bf9b02d04ddb6b936c
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spelling	oai:doaj.org-article:3f96f96faee244bf9b02d04ddb6b936c2021-11-15T05:36:47ZDynamic dichotomy of accumbal population activity underlies cocaine sensitization10.7554/eLife.660482050-084Xe66048https://doaj.org/article/3f96f96faee244bf9b02d04ddb6b936c2021-10-01T00:00:00Zhttps://elifesciences.org/articles/66048https://doaj.org/toc/2050-084XLocomotor sensitization (LS) is an early behavioral adaptation to addictive drugs, driven by the increase of dopamine in the Nucleus Accumbens (NAc). However, the effect on accumbal population activity remains elusive. Here, we used single-cell calcium imaging in mice to record the activity of dopamine-1-receptor (D1R) and dopamine-2-receptor (D2R) expressing spiny projection neurons (SPNs) during cocaine LS. Acute exposure to cocaine elevated D1R SPN activity and reduced D2R SPN activity, albeit with high variability between neurons. During LS, the number of D1R and D2R neurons responding in opposite directions increased. Moreover, preventing LS by inhibition of the ERK signaling pathway decreased the number of cocaine responsive D1R SPNs, but had little effect on D2R SPNs. These results indicate that accumbal population dichotomy is dynamic and contains a subgroup of D1R SPNs that eventually drives LS. Insights into the drug-related activity dynamics provides a foundation for understanding the circuit-level addiction pathogenesis.Ruud van ZessenYue LiLucile Marion-PollNicolas HuloJérôme FlakowskiChristian LüschereLife Sciences Publications Ltdarticlenucleus accumbensdopaminespiny projection neuroncocainecalcium imagingpopulation codingMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nucleus accumbens dopamine spiny projection neuron cocaine calcium imaging population coding Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	nucleus accumbens dopamine spiny projection neuron cocaine calcium imaging population coding Medicine R Science Q Biology (General) QH301-705.5 Ruud van Zessen Yue Li Lucile Marion-Poll Nicolas Hulo Jérôme Flakowski Christian Lüscher Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
description	Locomotor sensitization (LS) is an early behavioral adaptation to addictive drugs, driven by the increase of dopamine in the Nucleus Accumbens (NAc). However, the effect on accumbal population activity remains elusive. Here, we used single-cell calcium imaging in mice to record the activity of dopamine-1-receptor (D1R) and dopamine-2-receptor (D2R) expressing spiny projection neurons (SPNs) during cocaine LS. Acute exposure to cocaine elevated D1R SPN activity and reduced D2R SPN activity, albeit with high variability between neurons. During LS, the number of D1R and D2R neurons responding in opposite directions increased. Moreover, preventing LS by inhibition of the ERK signaling pathway decreased the number of cocaine responsive D1R SPNs, but had little effect on D2R SPNs. These results indicate that accumbal population dichotomy is dynamic and contains a subgroup of D1R SPNs that eventually drives LS. Insights into the drug-related activity dynamics provides a foundation for understanding the circuit-level addiction pathogenesis.
format	article
author	Ruud van Zessen Yue Li Lucile Marion-Poll Nicolas Hulo Jérôme Flakowski Christian Lüscher
author_facet	Ruud van Zessen Yue Li Lucile Marion-Poll Nicolas Hulo Jérôme Flakowski Christian Lüscher
author_sort	Ruud van Zessen
title	Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
title_short	Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
title_full	Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
title_fullStr	Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
title_full_unstemmed	Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
title_sort	dynamic dichotomy of accumbal population activity underlies cocaine sensitization
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/3f96f96faee244bf9b02d04ddb6b936c
work_keys_str_mv	AT ruudvanzessen dynamicdichotomyofaccumbalpopulationactivityunderliescocainesensitization AT yueli dynamicdichotomyofaccumbalpopulationactivityunderliescocainesensitization AT lucilemarionpoll dynamicdichotomyofaccumbalpopulationactivityunderliescocainesensitization AT nicolashulo dynamicdichotomyofaccumbalpopulationactivityunderliescocainesensitization AT jeromeflakowski dynamicdichotomyofaccumbalpopulationactivityunderliescocainesensitization AT christianluscher dynamicdichotomyofaccumbalpopulationactivityunderliescocainesensitization
_version_	1718428546697789440

Dynamic dichotomy of accumbal population activity underlies cocaine sensitization

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