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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/66048 |
| _version_ | 1797998431636029440 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T10:48:39Z |
| format | Article |
| id | doaj.art-3f96f96faee244bf9b02d04ddb6b936c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:48:39Z |
| publishDate | 2021-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3f96f96faee244bf9b02d04ddb6b936c2022-12-22T04:28:59ZengeLife Sciences Publications LtdeLife2050-084X2021-10-011010.7554/eLife.66048Dynamic dichotomy of accumbal population activity underlies cocaine sensitizationRuud van Zessen0https://orcid.org/0000-0001-5634-6922Yue Li1Lucile Marion-Poll2https://orcid.org/0000-0003-4652-9797Nicolas Hulo3https://orcid.org/0000-0003-2640-636XJérôme Flakowski4https://orcid.org/0000-0002-6457-3022Christian Lüscher5https://orcid.org/0000-0001-7917-4596Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandDepartment of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandDepartment of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandInstitute of Genetics and Genomics of Geneva (IGE3), University of Geneva, Geneva, SwitzerlandDepartment of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandDepartment of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Clinic of Neurology, Dept. of Clinical Neurosciences, Geneva University Hospital, Geneva, SwitzerlandLocomotor 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.https://elifesciences.org/articles/66048nucleus accumbensdopaminespiny projection neuroncocainecalcium imagingpopulation coding |
| spellingShingle | Ruud van Zessen Yue Li Lucile Marion-Poll Nicolas Hulo Jérôme Flakowski Christian Lüscher Dynamic dichotomy of accumbal population activity underlies cocaine sensitization eLife nucleus accumbens dopamine spiny projection neuron cocaine calcium imaging population coding |
| title | 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_short | Dynamic dichotomy of accumbal population activity underlies cocaine sensitization |
| title_sort | dynamic dichotomy of accumbal population activity underlies cocaine sensitization |
| topic | nucleus accumbens dopamine spiny projection neuron cocaine calcium imaging population coding |
| url | https://elifesciences.org/articles/66048 |
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