# Anorexia neural-circuit delineation

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $304,780

## Abstract

Abstract/Summary
The loss of appetite (anorexia) associated with eating too much, food poisoning, and nausea is
mediated by a neural circuit that starts with activation of vagal afferents, which activate brain
stem nuclei and then neurons that express calcitonin-gene-related protein (CGRP) in the
parabrachial nucleus (PBN). Transient activation of these CGRPPBN neurons by chemogenetic
or optogenetic means is sufficient to inhibit feeding and to induce conditioned taste aversion, the
phenomenon by which animals learn to avoid foods that make them sick. Chronic activation of
CGRPPBN neurons by various genetic manipulations can result in starvation. Chronic activation
of these neurons, as occurs during illnesses such as cancer, promotes anorexia. The CGRPPBN
neurons project their axons to forebrain structures, including the central nucleus of the
amygdala (CeA). Photoactivation of CGRPPBN axon terminals expressing channelrhodopsin in
the CeA also inhibits feeding. This grant proposes to establish the molecular identity of the
neurons in the CeA (and possibly other brain regions) that mediate anorexia and then extend
the neural circuit by molecular characterization of the neurons that are downstream of the CeA
neurons. Thus, this research will extend the ‘anorexia neural circuit’ by at least two nodes. The
molecular profile will be determined by quantification of all mRNAs being translated by the
neurons at each of these nodes. That information will provide valuable clues for extending the
neural circuit and devising therapeutic solutions to anorexia caused by chronic illness. The
results of these experiments will also provide a blueprint for understanding how memories of
food-related illness and nausea are established.

## Key facts

- **NIH application ID:** 10169396
- **Project number:** 5R01DA024908-14
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Richard D. Palmiter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $304,780
- **Award type:** 5
- **Project period:** 2007-09-25 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169396

## Citation

> US National Institutes of Health, RePORTER application 10169396, Anorexia neural-circuit delineation (5R01DA024908-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10169396. Licensed CC0.

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