Cue- versus reward-encoding basolateral amygdala projections to nucleus accumbens

In substance use disorders, drug use as unconditioned stimulus (US) reinforces drug taking. Meanwhile, drug-associated cues (conditioned stimulus, CS) also gain incentive salience to promote drug seeking. The basolateral amygdala (BLA) is implicated in both US- and CS-mediated responses. Here, we show that two genetically distinct BLA neuronal types, expressing Rspo2 versus Ppp1r1b, respectively, project to the nucleus accumbens (NAc) and form monosynaptic connections with both dopamine D1 and D2 receptor-expressing neurons. While intra-NAc stimulation of Rspo2 or Ppp1r1b presynaptic terminals establishes intracranial self-stimulation (ICSS), only Ppp1r1b-stimulated mice exhibit cue-induced ICSS seeking. Furthermore, increasing versus decreasing the Ppp1r1b-to-NAc, but not Rspo2-to-NAc, subprojection increases versus decreases cue-induced cocaine seeking after cocaine withdrawal. Thus, while both BLA-to-NAc subprojections contribute to US-mediated responses, the Ppp1r1b subprojection se...

在物质使用障碍中，药物使用作为无条件刺激（unconditioned stimulus, US）可强化药物摄取行为。与此同时，与药物相关的线索（条件刺激，conditioned stimulus, CS）也会获得激励显著性，进而促进药物觅求行为。基底外侧杏仁核（basolateral amygdala, BLA）参与介导了无条件刺激与条件刺激相关的神经反应。本研究发现，两种基因表达特征各异的基底外侧杏仁核神经元亚型——分别表达Rspo2与Ppp1r1b——会投射至伏隔核（nucleus accumbens, NAc），并与表达多巴胺D1和D2受体的神经元形成单突触连接。尽管激活Rspo2或Ppp1r1b型神经元的伏隔核内突触前末梢可建立颅内自我刺激（intracranial self-stimulation, ICSS）行为，但仅Ppp1r1b型神经元激活的小鼠会表现出线索诱导的颅内自我刺激觅求行为。进一步研究表明，增强或削弱Ppp1r1b至伏隔核的亚投射（而非Rspo2至伏隔核的亚投射），会分别提升或降低可卡因戒断后线索诱导的可卡因觅求行为。综上，尽管两条基底外侧杏仁核至伏隔核的亚投射均参与无条件刺激介导的反应，但Ppp1r1b亚投射则负责……