Domingues Ana Verónica, Carvalho Tawan T A, Martins Gabriela J, Correia Raquel, Coimbra Bárbara, Bastos-Gonçalves Ricardo, Wezik Marcelina, Gaspar Rita, Pinto Luísa, Sousa Nuno, Costa Rui M, Soares-Cunha Carina, Rodrigues Ana João
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Nat Commun. 2025 Jan 2;16(1):59. doi: 10.1038/s41467-024-55269-9.
The nucleus accumbens (NAc) is a key brain region for motivated behaviors, yet how distinct neuronal populations encode appetitive or aversive stimuli remains undetermined. Using microendoscopic calcium imaging in mice, we tracked NAc shell D1- or D2-medium spiny neurons' (MSNs) activity during exposure to stimuli of opposing valence and associative learning. Despite drift in individual neurons' coding, both D1- and D2-population activity was sufficient to discriminate opposing valence unconditioned stimuli, but not predictive cues. Notably, D1- and D2-MSNs were similarly co-recruited during appetitive and aversive conditioning, supporting a concurrent role in associative learning. Conversely, when contingencies changed, there was an asymmetric response in the NAc, with more pronounced changes in the activity of D2-MSNs. Optogenetic manipulation of D2-MSNs provided causal evidence of the necessity of this population in the extinction of aversive associations. Our results reveal how NAc shell neurons encode valence, Pavlovian associations and their extinction, and unveil mechanisms underlying motivated behaviors.
伏隔核（NAc）是动机行为的关键脑区，但不同神经元群体如何编码奖赏性或厌恶性刺激仍未明确。我们利用小鼠体内的显微内窥镜钙成像技术，在暴露于具有相反效价的刺激及联想学习过程中，追踪伏隔核壳部D1或D2型中等多棘神经元（MSNs）的活动。尽管单个神经元编码存在漂移现象，但D1和D2群体活动均足以区分具有相反效价的无条件刺激，却无法区分预测线索。值得注意的是，在奖赏性和厌恶性条件反射过程中，D1和D2型MSNs同样会被共同激活，这支持了它们在联想学习中具有并行作用的观点。相反，当意外情况发生变化时，伏隔核会出现不对称反应，D2型MSNs的活动变化更为明显。对D2型MSNs进行光遗传学操控，为该群体在厌恶性联想消退中的必要性提供了因果证据。我们的研究结果揭示了伏隔核壳部神经元如何编码效价、经典条件反射及其消退，并揭示了动机行为背后的机制。
