# Project 2: Regulation, circuitry, and function of non-aversive and aversive PBN satiety systems

> **NIH NIH P01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $473,891

## Abstract

Hypothalamic circuits mediate their feeding and energy balance effects in part via
descending projections to brainstem satiety systems. Cells within the parabrachial nucleus (PBN)
respond both to descending hypothalamic control and to ascending inputs from the nucleus of the
solitary tract (NTS) that encode peripheral satiety signals emanating from the gastrointestinal
tract. Signals of gut status (including distention, nutrient content, etc.) travel via the vagus nerve
and the circulation and converge on the area postrema (AP) and nucleus of the solitary tract
(AP/NTS). The AP/NTS conveys this gut status information to the PBN and other rostral centers.
The PBN relays this information rostrally to the central nucleus of the amygdala (CeA) and
elsewhere to promote satiety. CeA-projecting CGRP-expressing PBN (CGRPPBN) neurons
promote a negative-valence anorexia and play a requisite role in the generation of conditioned
taste aversion to noxious GI stimuli. The observations that local administration of glucagon-like
peptide 1 (GLP-1) receptor agonists into the PBN suppress feeding without aversion and that
descending Mc4R+ hypothalamic inputs to the PBN suppress feeding with positive valence
suggests the distinct nature of rewarding satiety systems and aversive anorexia circuits within the
PBN. Importantly circuits mediating aversive symptoms such as nausea are intermingled with
satiety systems within the PBN and this interaction limits medical therapies that target the
brainstem satiety circuits for therapeutic advantage. Thus, it is crucial to distinguish the brain
systems that encode satiety from those that promote nausea and other aversive symptoms.
 A thorough molecular-functional characterization of PBN cell types is lacking and is critical
to understanding the acute and chronic regulation of feeding and anorexia. Our preliminary data
reveal that glucagon-like peptide 1 receptor (GLP-1R)-expressing PBN neurons(GLP-1RPBN) are
distinct from aversive CGRPPBN neurons and suppress feeding without aversion. We hypothesize
that GLP-1RPBN cells are activated by nonaversive satiety signals that convey positive valence,
whereas CGRPPBN cells are activated by and mediate the response to aversive GI stimuli. This
proposal will test the hypotheses that 1) non-aversive GLP-1RPBN and aversive CGRPPBN neurons
lie in distinct circuits and respond to differing stimuli, 2) GLP-1RPBN and CGRPPBN neurons activate
different downstream circuits and mediate distinct physiological and behavioral functions and 3)
and GLP-1RPBN and CGRPPBN neurons are differentially required for the physiological and
pharmacological control of food intake.

## Key facts

- **NIH application ID:** 10018886
- **Project number:** 5P01DK117821-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** DAVID P OLSON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $473,891
- **Award type:** 5
- **Project period:** 2019-09-20 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018886

## Citation

> US National Institutes of Health, RePORTER application 10018886, Project 2: Regulation, circuitry, and function of non-aversive and aversive PBN satiety systems (5P01DK117821-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10018886. Licensed CC0.

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