TY - JOUR TI - Dynamic dichotomy of accumbal population activity underlies cocaine sensitization AU - van Zessen, Ruud AU - Li, Yue AU - Marion-Poll, Lucile AU - Hulo, Nicolas AU - Flakowski, Jérôme AU - Lüscher, Christian A2 - Gittis, Aryn H A2 - Taffe, Michael A VL - 10 PY - 2021 DA - 2021/10/05 SP - e66048 C1 - eLife 2021;10:e66048 DO - 10.7554/eLife.66048 UR - https://doi.org/10.7554/eLife.66048 AB - 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. KW - nucleus accumbens KW - dopamine KW - spiny projection neuron KW - cocaine KW - calcium imaging KW - population coding JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -