# A Novel Node in Threat Response Neurocircuitry: VGLUT2 Positive Supramammillary Neurons Projecting to Preoptic Hypothalamus

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2022 · $192,123

## Abstract

Dr. Aaron Norris MD, PhD, is a neuroscientist and neuroanesthesiologist with the long-term goal to be an
independent investigator focused on neural circuits and mechanisms regulating stress and arousal. His research
background includes ion channel physiology, circadian neurobiology and, most recently, neural circuits
regulating stress and arousal. Dr. Norris is a member of Dr. Gereau’s lab in the Department of Anesthesiology
at Washington University. The lab, department, and university provide exceptional training environments. In the
Gereau lab, Dr. Norris will receive training in state-of-the-art optogenetics, viral neural circuit tracing and mouse
behavioral models. Working with his co-mentor, Dr. Dougherty, he will gain experience in neurotranscriptomics.
The department of anesthesiology provides a rich training environment with nearly 20 early stage physician–
scientists. The department also houses active labs working on circuit related neuroscience questions using
similar techniques. The proposed project focuses on a neuronal population in supramammillary nucleus (SuM).
Dr. Norris used genetic and retrograde viral tools to identify a previously unrecognized population of VGLUT2
positive neurons in SuM that project to the preoptic area of the hypothalamus (SuM→POA). Preliminary data
suggest that this uncharacterized population of neurons is a critical node in mediating active responses to
threatening stressors. The proposed experiments will use cutting-edge fiber photometry, chemogenetics,
optogenetics, viral tools, and molecular transcriptomic techniques to 1) anatomically and transcriptionally define
the SuM→POA neural population; 2) determine whether innate, environmental and learned threats activate
SuM→POA neurons; and 3) establish whether VGLUT2 positive SuM→POA neurons are sufficient and
necessary for active responses to threatening stressors. We will test the hypotheses: 1) individual neurons in
SuM project to POA and anatomically distant brain regions; 2) VGLUT2 positive SuM→POA neurons are
activated in vivo by predator cues, force swimming, and learned threat cues; 3) activation of VGLUT2 positive
SuM→POA neurons encodes a negative valence, evokes active innate defensive behaviors, drives instrumental
goal-directed behaviors, increases active coping behaviors but does not increase anxiety-like behaviors; 4)
inhibition of VGLUT2 positive SuM→POA neurons decreases active coping behaviors evoked by acute
threatening stimuli. The results of these experiments will fundamentally inform our understanding of the
neurocircuitry involved in threat response. The proposed plan will provide Dr. Norris with the training, mentorship,
and experience to transition to independence in a timely manner and obtain R01 funding.

## Key facts

- **NIH application ID:** 10464903
- **Project number:** 5K08MH119538-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Aaron J Norris
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $192,123
- **Award type:** 5
- **Project period:** 2019-09-13 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464903

## Citation

> US National Institutes of Health, RePORTER application 10464903, A Novel Node in Threat Response Neurocircuitry: VGLUT2 Positive Supramammillary Neurons Projecting to Preoptic Hypothalamus (5K08MH119538-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10464903. Licensed CC0.

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