PT  - JOURNAL ARTICLE
AU  - Emily A. Kelly
AU  - V. Kaye Thomas
AU  - Apoorva Indraghanty
AU  - Julie L. Fudge
TI  - Perigenual and Subgenual Anterior Cingulate Afferents Converge on Common Pyramidal Cells in Amygdala Subregions
AID  - 10.1101/2021.05.07.443119
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.07.443119
4099  - http://biorxiv.org/content/early/2021/05/09/2021.05.07.443119.short
4100  - http://biorxiv.org/content/early/2021/05/09/2021.05.07.443119.full
AB  - The subgenual (sgACC) and pregenual (pgACC) anterior cingulate are important afferents of the amygdala, with different cytoarchitecture, connectivity, and function. The sgACC is associated with arousal mechanisms linked to salient cues, while the pgACC is engaged in conflict decision-making, including in social contexts. We explored their influence on the nonhuman primate amygdala. After placing same-size, small volume tracer injections into sgACC and pgACC of the same hemisphere, we examined terminal fiber distribution to better understand how these different functional systems communicate with the amygdala. The sgACC has broad-based termination patterns in the amygdala; the pgACC has a more restricted pattern which was always nested in sgACC terminals. Overlap occurred in subregions of the accessory basal and basal nuclei, termed ‘hotspots’. In triple-labeling confocal studies, the majority of randomly selected CAMKIIα (+) cells (putative amygdala glutamatergic neurons) in ‘hotspots’ received dual contacts from the sgACC and pgACC. The ratio of dual contacts occurred over a surprisingly narrow range, suggesting a consistent, tight balance of afferent contacts on postsynaptic neurons. We also found that large boutons, which are associated with greater synaptic strength, were approximately 3 times more frequent on sgACC versus pgACC axon terminals, consistent with a ‘driver’ function. Together, the results reveal a nested interaction in which pgACC (‘conflict/social monitoring’) terminals converge with the broader sgACC (‘salience’) terminals at both the mesoscopic and cellular level in ‘hotspots’. pgACC and sgACC convergence suggests a flexible way whereby shifts in arousing cues can rapidly influence cognitive computations such as social monitoring.Significance statement The subgenual cingulate (sgACC), which mediates ‘internal salience’, perigenual cingulate (pgACC), which mediates ‘conflict monitoring’, and the amygdala are dysregulated in human mood and anxiety disorders. Using dual tracer injections in the same monkey, we found that sgACC inputs broadly project in the amygdala; in contrast, pgACC terminal fields were more restricted and nested in zones containing sgACC terminals (‘hotspots’). In ‘hotspots’, most CAMKIIα + (excitatory) amygdala neurons were contacted by terminals from both regions, with a consistent ratio of pgACC: sgACC dual contacts, suggesting a strict balance of afferent inputs. The interdependency of pgACC and sgACC information streams suggests that shifting ‘internal arousal’ states can directly shape responses in amygdala neurons involved in higher cognitive networks.Competing Interest StatementThe authors have declared no competing interest.