# A Common Neuronal Pathway for the Behavioral and Neuroendocrine Response to Potential Threat

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $39,543

## Abstract

Project Summary/Abstract:
In the face of a potential threat, individual differences in risk-taking behaviors are often accompanied by
corresponding differences in hypothalamic-pituitary-adrenal (HPA) axis activation. However, the underlying
neural circuitry that may provide a common pathway for both behavioral and neuroendocrine control has not
been explored. The long-term goal of this research is to identify the neural circuitry that provides this common
pathway for mediating both behavioral and neuroendocrine outputs in response to a potential threat. One
candidate for providing this shared pathway is the projection from ventral subiculum (vSUB) to anterior bed
nucleus of the stria terminalis (aBNST). The neuroanatomy of this projection consists of direct glutamatergic
projections sent from the vSUB to the aBNST, which in turn sends GABAergic projections to the
paraventricular nucleus (PVN) of the hypothalamus, the primary initiator of the stress response. Previous
studies have implicated both vSUB and BNST in risk-taking behavior and in HPA axis inhibition. The vSUB
sends scant projections to the PVN, suggesting that it relays its inhibitory effects on the HPA axis through a
relay structure such as BNST. Indeed, PVN projecting aBNST neurons show reduced activation in vSUB-
lesioned animals, suggesting that the aBNST may be the relay through which the vSUB provides HPA axis
inhibition. Furthermore, acute stress causes activation of vSUB neurons projecting to the aBNST and of PVN
projecting BNST neurons. Given these data, the vSUB-aBNST projection may provide a common pathway that
mediates both behavioral and neuroendocrine control under potential threat, which is the central hypothesis of
this proposal. In the first Aim, we will determine how calcium activity in the vSUB-aBNST projection relates to
risk-taking behavior and HPA axis activity in a potential threat paradigm. In the second Aim, we will determine
whether activation of the vSUB-alBNST projection during a potential threat paradigm alters risk-taking behavior
and HPA axis activity. The results will reveal the role of this projection in risk-taking behavior and HPA axis
regulation, potentially revealing a novel neural circuit as a common pathway for behavior and neuroendocrine
regulation.

## Key facts

- **NIH application ID:** 10492485
- **Project number:** 5F31MH126511-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Euphemia (Jena) Sabah Gewarges
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,543
- **Award type:** 5
- **Project period:** 2021-09-02 → 2024-09-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492485

## Citation

> US National Institutes of Health, RePORTER application 10492485, A Common Neuronal Pathway for the Behavioral and Neuroendocrine Response to Potential Threat (5F31MH126511-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10492485. Licensed CC0.

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