Description: Invasive tract-tracing studies in rats implicate a direct connection between the subiculum and bed nucleus of the stria terminalis (BNST) as a key component of neural pathways mediating hippocampal regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. A clear characterisation of the connections linking the subiculum and BNST in humans and non-human primates is lacking. To address this, we first delineated the projections from the subiculum to the BNST using anterograde tracers injected into macaque monkeys, revealing evidence for a monosynaptic subiculum-BNST projection involving the fornix. Second, we used in vivo diffusion MRI tractography in macaques and humans to demonstrate substantial subiculum connectivity to the BNST in both species. This connection was primarily mediated through the fornix, with additional connectivity via the amygdala, consistent with rodent anatomy. Third, utilising the twin-based nature of our human sample, we found that microstructural properties of these tracts are moderately heritable (h2 ~ 0.5). In a final analysis, we found no evidence of any significant association between subiculum-BNST tract microstructure and indices of perceived stress/dispositional negativity and alcohol use, derived from PCA decomposition of self-report data. We did however find subiculum-BNST tract microstructure associations with BMI, age, and sex. Our findings address a key translational gap in our knowledge of the neurocircuitry regulating stress.
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