# Defining locus coeruleus-norepinephrine (LC-NE) circuits in feeding

> **NIH NIH R00** · UNIVERSITY OF CONNECTICUT STORRS · 2021 · $249,000

## Abstract

PROJECT SUMMARY
Overeating is a major contributor to excessive weight gain, involving the hypothalamus and innervating brain
systems that control reward, motivation, learning and emotion. Accumulating clinical data indicate that
disruptions to the norepinephrine (NE) signaling system underlie key aspects of obesity. NE stimulants are
currently the most effective therapies for weight loss, but the precise neural circuits that underlie this regulation
of feeding remain largely unresolved. The goal of this proposed K99-R00 research is to dissect the role of the
locus coeruleus (LC) to lateral hypothalamus (LHA) noradrenergic circuit in feeding and dietary obesity. The
central hypothesis is that increased LC-NE activity will suppress feeding through inhibition of LHA hunger-
promoting neurons. The basis for this hypothesis comes from the candidate’s preliminary data, together with
published findings. To test the central hypothesis, the candidate will carry out three Specific Aims: (1) Identify
the natural population activity patterns of LC-NE neurons during feeding behaviors; (2) Identify the hypothalamic
cell types involved in LC-NE suppression of feeding; and (3) Determine the involvement of the LC-LHA
noradrenergic circuit in the physiology and treatment of obesity. These aims will be accomplished using state-
of-the-art technologies developed and used by the candidate’s mentoring team, including wireless fiber
photometry to visualize neuronal activity, optogenetics tools to manipulate neural activity, and devices for high-
resolution measurements of feeding behavior. This career development award will build on the candidate’s skills
in behavioral pharmacology and systems neuroscience, and will facilitate the candidate’s long-term career goal
of developing an independent research program focused on the NE circuits underlying feeding. The ultimate
goal of this research is to inform the development of novel treatment strategies that activate specific LC-NE
circuits to suppress feeding without incurring the off-target side effects observed using strategies that affect the
entire noradrenergic system.

## Key facts

- **NIH application ID:** 10369832
- **Project number:** 4R00DK119586-03
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Natale R Sciolino
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2021-05-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369832

## Citation

> US National Institutes of Health, RePORTER application 10369832, Defining locus coeruleus-norepinephrine (LC-NE) circuits in feeding (4R00DK119586-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10369832. Licensed CC0.

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