Acetylcholine is a robust neuromodulator of the limbic system and a critical regulator of arousal and emotions. The anterior cingulate cortex (ACC) and the amygdala (AMY) are key limbic structures that are both densely innervated by cholinergic afferents and interact with each other for emotional regulation. The ACC is composed of functionally distinct dorsal (A24), rostral (A32), and ventral (A25) areas that differ in their connections with the AMY. The structural substrates of cholinergic modulation of distinct ACC microcircuits and outputs to AMY are thought to depend on the laminar and subcellular localization of cholinergic receptors. The present study examines the distribution of muscarinic acetylcholine receptors, m1 and m2, on distinct excitatory and inhibitory neurons and on AMY-targeting projection neurons within ACC areas, via immunohistochemistry and injections of neural tracers into the basolateral AMY in adult rhesus monkeys of both sexes. We found that laminar densities of m1+ and m2+ expressing excitatory and inhibitory neurons depended on area and cell type. Among the ACC areas, ventral subgenual ACC A25 exhibited greater m2+ localization on presynaptic inhibitory axon terminals and greater density of m1+ and m2+ expressing AMY-targeting (tracer+) pyramidal neurons. These patterns suggest robust cholinergic disinhibition and potentiation of amygdalar outputs from the limbic ventral ACC, which may be linked to the hyperexcitability of this subgenual ACC area in depression. These findings reveal the anatomical substrate of diverse cholinergic modulation of specific ACC microcircuits and amygdalar outputs that mediate cognitive–emotional integration and dysfunctions underlying stress and affective disorders.

乙酰胆碱是边缘系统的强大神经调节剂，也是唤醒和情绪的关键调节剂。前扣带皮层 (ACC) 和杏仁核 (AMY) 是关键的边缘结构，它们都受到胆碱能传入神经的密集支配，并相互作用来调节情绪。 ACC 由功能不同的背侧 (A24)、喙侧 (A32) 和腹侧 (A25) 区域组成，这些区域与 AMY 的连接不同。不同 ACC 微电路的胆碱能调节和 AMY 输出的结构底物被认为取决于胆碱能受体的层状和亚细胞定位。本研究通过免疫组织化学和向成年两性恒河猴的基底外侧 AMY 注射神经示踪剂，检查了毒蕈碱乙酰胆碱受体 m1 和 m2 在不同的兴奋性和抑制性神经元以及 ACC 区域内 AMY 靶向投射神经元上的分布。 。我们发现表达兴奋性和抑制性神经元的 m1+ 和 m2+ 的层流密度取决于区域和细胞类型。在 ACC 区域中，腹侧膝下 ACC A25 在突触前抑制性轴突末端表现出更大的 m2+ 定位，并且表达 AMY 靶向（示踪剂+）锥体神经元的 m1+ 和 m2+ 密度更高。这些模式表明，边缘腹侧 ACC 的杏仁核输出存在强烈的胆碱能去抑制和增强，这可能与抑郁时膝下 ACC 区域的过度兴奋有关。这些发现揭示了特定 ACC 微电路和杏仁核输出的不同胆碱能调节的解剖学基础，这些胆碱能调节介导认知情绪整合以及压力和情感障碍潜在的功能障碍。