Subiculum – BNST Structural Connectivity in Humans and Macaques

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.

Inhibitory hippocampo–septal projection controls locomotion and exploratory behavior

Although the hippocampus is generally considered a cognitive center for spatial representation, learning and memory, increasing evidence supports its roles in regulation of locomotion. However, the neuronal mechanisms of hippocampal regulation of locomotion and exploratory behavior remain unclear. Here we found that the inhibitory hippocampo-septal projection bi–directionally controls locomotion speed of mice. Pharmacogenetic activation of these septum–projecting interneurons decreased locomotion and exploratory behavior. Similarly, activation of the hippocampus–originated inhibitory terminal in the medial septum reduced locomotion. On the other hand, inhibition of the hippocampus–originated inhibitory terminal increased locomotion. The locomotion-regulative roles were specific to the septal projecting interneurons as activation of hippocampal interneurons projecting to the retrosplenial cortex did not change animal locomotion. Therefore, this study reveals a specific long-range inhibitory output from the hippocampus in the regulation of animal locomotion.

Remembering to eat: hippocampal regulation of meal onset

A wide variety of species, including vertebrate and invertebrates, consume food in bouts (i.e., meals). Decades of research suggest that different mechanisms regulate meal initiation (when to start eating) versus meal termination (how much to eat in a meal, also known as satiety). There is a very limited understanding of the mechanisms that regulate meal onset and the duration of the postprandial intermeal interval (ppIMI). In the present review, we examine issues involved in measuring meal onset and some of the limited available evidence regarding how it is regulated. Then, we describe our recent work indicating that dorsal hippocampal neurons inhibit meal onset during the ppIMI and describe the processes that may be involved in this. We also synthesize recent evidence, including evidence from our laboratory, suggesting that overeating impairs hippocampal functioning and that impaired hippocampal functioning, in turn, contributes to the development and/or maintenance of diet-induced obesity. Finally, we identify critical questions and challenges for future research investigating neural controls of meal onset.