# The AgRP / POMC -> Paraventricular (PVH) -> Parabrachial (PBN) -> Limbic/Reward Satiety Circuit

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $510,447

## Abstract

The AgRP / POMC à Paraventricular (PVH) à Parabrachial (PBN) à Limbic/Reward Satiety Circuit
Because obesity is prevalent and is associated with morbidity and mortality, it is important to understand how
energy balance regulates hunger / satiety, and ultimately causes or curtails eating. While much has been
learned over the past 25 years including the roles of leptin action in the mediobasal hypothalamus, AgRP and
POMC neurons in the ARC, and downstream satiety neurons in the PVH, we still do not know how this energy
balance-regulated circuit controls eating. This is because we do not know what lies beyond the ARCàPVH
circuit. While regulation of emotional valence and reward must be involved, because ARC and PVH neurons
don’t directly engage brain sites controlling these processes, we are still very much in the dark. The goal of
our studies is to address this huge gap in our knowledge. Given that parabrachial (PBN) neurons are
downstream of the ARCàPVH circuit, and given that PBN neurons project to limbic / reward sites, we propose
that PBN satiety neurons are the “missing link”. Barriers exist, however, that have prevented us from bridging
this gap between the ARCàPVH circuit and the limbic / reward “higher brain sites”. They are:
1: We do not know the precise identity of the PVH satiety neurons. This hampers efforts to selectively image,
manipulate and map these neurons, and creates confusion between studies utilizing different PVH “markers”.
2: The PBN is a complex hub that routes many different interoceptive signals to higher brain sites – including
that related to energy balance. This complexity, and the inability to penetrate it, is a huge barrier. Such efforts
would be greatly aided by: a) knowing the inventory of transcriptionally unique neurons that exist in the PBN,
b) the PBN sub-nuclei “addresses” of each of these neurons, and c) having tools to “access” these neurons.
3: Related to “barrier 2”, we do not know the identity of the “missing link” PBN satiety neurons.
To address these barriers, this grant proposes the following three aims:
Aim 1: To build a transcriptomic neuronal atlas of the PVH, and to identify and study the specific neurons that
correspond to the two genetically distinct PVH satiety neurons (one marked by Mc4r, the other by Pdyn).
Aim 2: To build a transcriptomic neuronal atlas of the PBN, and use In Situ Sequencing to spatially assign
each PBN neuron to its PBN sub-nuclei “address”. This atlas will be a valuable resource for all efforts aimed at
understanding the “routing” of interoceptive information by the PBN – including that related to energy balance.
Aim 3: To identify PBN satiety neurons and elucidate the neural mechanisms by which they regulate hunger /
satiety and emotional valence. Given that these PBN neurons project to “higher sites” controlling emotional
valence and reward, the discovery of these PBN satiety neurons provides the means for mechanistically
understanding how caloric deficiency ultimately co...

## Key facts

- **NIH application ID:** 10414958
- **Project number:** 5R01DK075632-17
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** BRADFORD B LOWELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $510,447
- **Award type:** 5
- **Project period:** 2006-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414958

## Citation

> US National Institutes of Health, RePORTER application 10414958, The AgRP / POMC -> Paraventricular (PVH) -> Parabrachial (PBN) -> Limbic/Reward Satiety Circuit (5R01DK075632-17). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10414958. Licensed CC0.

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