Subiculum–BNST structural connectivity in humans and macaques

Samuel C. Berry, Andrew D. Lawrence, Thomas M. Lancaster, Chiara Casella, John P. Aggleton, Mark Postans

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2 Citations (SciVal)


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 carried by 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 were 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. Our findings address a key translational gap in our knowledge of the neurocircuitry regulating stress.

Original languageEnglish
Article number119096
Number of pages17
Early online date15 Mar 2022
Publication statusPublished - 30 Jun 2022

Bibliographical note

Funding Information:
This project was funded by a Wellcome Trust PhD studentship awarded to Samuel Berry, grant reference: 215194/Z/19/Z. Human data were provided [in part] by the Human Connectome Project, WU?Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. Our thanks to Shen K, Bezgin G, Schirner M, Ritter P, Everling S, McIntosh AR & OpenNEURO ([Dataset] doi: 10.18112/openneuro.ds001875.v1.0.3) for the collection and hosting of the non-human primate neuroimaging data. Special thanks to Christopher Dillingham at Cardiff University for producing the bright field, dark field, and overlay images (Fig. 4).


  • Bed nucleus of the stria terminalis (BNST/BST)
  • Diffusion Magnetic resonance imaging (dMRI)
  • Hippocampus
  • Hypothalamic pituitary adrenal (HPA) axis
  • Non-human primates (NHP)
  • Stress
  • Subiculum

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience


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