Anterior cingulate cortex projections to the amygdala in primates: topographic and layer-specific organization underlying emotion and mood regulation

Abstract

Emotion and mood regulation critically depends on interactions between the anterior cingulate cortex (ACC) and the amygdala. However, the detailed architecture of ACC projections to their major targets, the basal (BA) and accessory (AcBA) basal nuclei of the amygdala, remains unclear. To address this issue, a combined retrograde and anterograde tracing with viral vectors were performed in macaques of either sex to map the projection patterns from the pregenual (pgACC), subgenual (sgACC), and dorsal (dACC) subareas. Data revealed that ACC neurons projecting to the BA arose predominantly from the superficial layers (II/III) of all subareas and the deep layers (V/VI) of the sgACC, whereas ACC neurons projecting to the AcBA originated mainly in the deep layers of the sgACC and dACC. The present study defines the topographic and layer-specific organization of ACC–amygdala connectivity in primates and subserves to provide an anatomical basis for future causal and translational approaches, such as targeted interventions against ACC-related mood disorders. Significance Statement Emotion and mood regulation critically depends on interactions between the anterior cingulate cortex (ACC) and the amygdala, and their dysfunctions have been implicated in mood disorders such as depression. However, the detailed organization of primate ACC–amygdala circuitry remains to be fully understood. Notably, the existence of projections from the pregenual ACC (pgACC) to the basal nucleus of the amygdala (BA) has been controversial. Using viral vector-based neural tracings in macaques, we have identified a distinct pgACC–BA pathway and shown that this pathway arises predominantly from the superficial layers of the cortex. Such unexpected laminar origin, atypical for cortico–subcortical projections, reveals a previously unrecognized circuit architecture and challenges prevailing models of cortico–amygdala linkage involved in mood disorders.