Dynamic dichotomy of accumbal population activity underlies cocaine sensitization

eLife

Jérôme Flakowski¹  Yue Li¹  Lucile Marion-Poll¹  Ruud van Zessen¹  Christian Lüscher²  Nicolas Hulo³ 

[1] Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland;Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland;Clinic of Neurology, Dept. of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland;Institute of Genetics and Genomics of Geneva (IGE3), University of Geneva, Geneva, Switzerland;

关键词: nucleus accumbens;    dopamine;    spiny projection neuron;    cocaine;    calcium imaging;    population coding;    Mouse;   

DOI  :  10.7554/eLife.66048

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY