# Deciphering Neural Circuits Underlying Hippocampal Suppression of Food Intake

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $417,500

## Abstract

Project Summary
 Anorexia nervosa (AN) and its associated complications impose a huge burden to our society. However, the
cellular and circuits mechanisms underlying this eating disorder are largely unknown, and effective treatments
are still lacking. At its core, anorexia nervosa is an emotional disorder characterized by persistent and severe
self-restriction of food intake and commonly co-occurring with anxiety. Most work has focused on hypothalamic
homeostatic control of food intake. An important but poorly understood element is the emotional aspect of food
intake. To further our understandings of the neural mechanisms of anorexia nervosa and develop new clinical
therapeutic strategies to treat this eating disorder, it thus is critical to decipher the neural circuits underlying this
disorder and determine whether the neural circuits for anorexia and anxiety are distinct or overlapping. Our
long-term goal is to enable the development of novel targets to correct or reverse eating disorders, such as
anorexia nervosa. Our overall objective for this application is to dissect the neural circuits that mediate the
ventral hippocampal anorexigenic effects on food intake and their anxiogenic effects. Our central hypothesis is
that the ventral hippocampus suppresses food intake by projecting glutamatergic inputs to the lateral septum
(LS) to activate GABAergic neurons in the LS, which subsequently inactivates GABAergic neurons in the
lateral hypothalamus (LH). Our hypothesis has been formulated on the basis of our recent study and our
preliminary data which will be detailed in the Approach section. The work of Jennings et al. (2014) and Wu et
al. (2015) provides additional support for this hypothesis. The rational for the proposed research is that, once
the neural circuits underlying the ventral hippocampus (vHPC)-based anorexia nervosa are identified, it may be
feasible to pharmacologically manipulate them to treat this disorder, and potentially other eating disorders.
 To accomplish our goals, we have assembled a research team that combines expertise of feeding and
emotions. To test our central hypothesis and thereby accomplish our overall objective, we will carry out three
Specific Aims: (1) Identify and characterize LS neuron populations mediating vHPC suppression of feeding; (2)
Identify LS neuron populations that relay the vHPC appetitive suppressive information to LH; (3) Determine the
anxiogenic effects of the neural circuits mediating the vHPC-based anorexia. Collectively, the vHPC-based
anorexia and anxiety and the involved neural circuits will be studied using state-of-the-art methodologies that
include optogenetic-assisted circuit mapping, single-cell gene analysis, feeding and emotional behavioral tests,
chemogenetic-and optogenetic neural manipulations. Results using these cutting-edge methods will give us
unprecedented access to understanding the cellular and circuit mechanisms of the vHPC-based anorexia
nervosa. The proposed research repr...

## Key facts

- **NIH application ID:** 9899824
- **Project number:** 5R01MH109441-07
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Yunlei Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,500
- **Award type:** 5
- **Project period:** 2016-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899824

## Citation

> US National Institutes of Health, RePORTER application 9899824, Deciphering Neural Circuits Underlying Hippocampal Suppression of Food Intake (5R01MH109441-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9899824. Licensed CC0.

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