PT  - JOURNAL ARTICLE
AU  - Samuel C. Berry
AU  - Andrew D. Lawrence
AU  - Thomas M. Lancaster
AU  - Chiara M. Casella
AU  - John P. Aggleton
AU  - Mark Postans
TI  - Subiculum – BNST Structural Connectivity in Humans and Macaques
AID  - 10.1101/2021.11.11.468209
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.11.11.468209
4099  - http://biorxiv.org/content/early/2021/11/13/2021.11.11.468209.short
4100  - http://biorxiv.org/content/early/2021/11/13/2021.11.11.468209.full
AB  - Invasive tract-tracing studies in rodents 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 complex 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 complex-BNST tract microstructure and indices of perceived stress/dispositional negativity and alcohol use, derived from principal component analysis decomposition of self-report data. We did, however, find subiculum complex-BNST tract microstructure associations with BMI, age, and sex. Our findings address a key translational gap in our knowledge of the neurocircuitry regulating stress.Competing Interest StatementThe authors have declared no competing interest.