Dynamic dichotomy of accumbal population activity underlies cocaine sensitization

Article Article scientifique Article Dynamic dichotomy of accumbal population activity underlies cocaine sensitization eng 2021-10-05 2021-10-05 author Van Zessen Ruud 0000-0001-5634-6922 858529 author Li Yue 892648 author Marion-Poll Lucile 0000-0003-4652-9797 959936 author Hulo Nicolas 0000-0003-2640-636X 29577 author Flakowski Jérôme 0000-0002-6457-3022 516449 author Luscher Christian 0000-0001-7917-4596 34378 e66048 10.7554/eLife.66048 34608866 2050-084X PMC8523149 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. Calcium imaging Cocaine Dopamine Mouse Neuroscience Nucleus accumbens Population coding Spiny projection neuron Animals Cocaine / pharmacology Dopaminergic Neurons / drug effects Dopaminergic Neurons / metabolism Female Locomotion / drug effects Male Mice, Inbred C57BL Mice, Transgenic Nucleus Accumbens / drug effects Nucleus Accumbens / metabolism Receptors, Dopamine D1 / metabolism Receptors, Dopamine D2 / metabolism Dewey 590 Dewey 616.8 Swiss National Science Foundation Emergence of compulsion in a mouse model of addiction 310030_189188 CH Project funding Swiss National Science Foundation Cellular determinants of subthalamic nucleus function CRSII5_186266 CH Programmes European Commission Convergence of positive and negative reinforcement in fentanyl addiction 883746 F-Addict EU H2020 23 Institut de génétique et de génomique 0DH 53 Département de neurosciences fondamentales 21A 61 Département des neurosciences cliniques 226 false 271 Mécanismes cellulaires de la dépendance et de l'addiction 520 https://zenodo.org/record/5507009#.YektsN_jKMo eLife 10 e7416078-8e71-4907-9895-748c5814b45d Article (Published version) Public Article-scientifique-from-europePmc.pdf 4241986 application/pdf CC BY dbc28ce3-77fb-45cf-885d-3960bd2032df Appendix Public elife-66048-transrepform1.docx 253243 application/vnd.openxmlformats-officedocument.wordprocessingml.document openAccess Centres et instituts / Institut de génétique et de génomique Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Dynamic dichotomy of accumbal population activity underlies cocaine sensitization	eLife			2021	290	271

Archive ouverte UNIGE

Marion-Poll, Lucile