Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Institute of Genetics and Genomics of Geneva (IGE3), University of Geneva, Geneva, Switzerland.
Elife. 2021 Oct 5;10:e66048. doi: 10.7554/eLife.66048.
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.
运动敏化（LS）是对成瘾药物的早期行为适应，其驱动力是伏隔核（NAc）中多巴胺的增加。然而，其对伏隔核群体活动的影响仍不清楚。在这里，我们使用单细胞钙成像技术在小鼠中记录了可卡因 LS 期间多巴胺-1-受体（D1R）和多巴胺-2-受体（D2R）表达的棘突投射神经元（SPN）的活性。急性暴露于可卡因会升高 D1R SPN 的活性并降低 D2R SPN 的活性，尽管神经元之间的变异性很高。在 LS 期间，对相反方向做出反应的 D1R 和 D2R 神经元的数量增加。此外，通过抑制 ERK 信号通路来阻止 LS 会减少对可卡因有反应的 D1R SPN 的数量，但对 D2R SPN 的影响很小。这些结果表明，伏隔核群体二分法是动态的，包含一组最终驱动 LS 的 D1R SPN。对与药物相关的活动动态的深入了解为理解电路水平的成瘾发病机制提供了基础。
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