# Forebrain Circuits and Control of Feeding Behavior by Learned Cues

> **NIH NIH R01** · BOSTON COLLEGE · 2020 · $399,510

## Abstract

Obesity has reached epidemic proportions and associated health consequences are alarming, but successful
treatment remains a significant challenge, because the underlying causes are complex. In addition to the
physiological energy and nutrient needs, external, environmental influences can drive appetite and eating
through cognitive and hedonic processes, independently from hunger. Substantial progress has been made in
our understanding the homeostatic regulation of food intake and body weight and the integration between
physiological and central mechanisms within the hypothalamic and brainstem circuitries. Much less is known
about the neural mechanisms mediating environmental influences, yet they are important in health and
disease. Cues from the environment can become signals for food through associative learning, and based on
that acquired ability can control feeding behavior. These cognitive processes enhance survival when they
function in concert with homeostatic control and their stimulatory effects may have been adaptive in the past
when energy resources were scarce. The developed world is rich in easily accessible palatable foods and
stimulatory effects of omnipresent food cues are maladaptive, as they drive overeating and weight gain. Thus,
determining the neural mechanisms underlying this cognitive, non-homeostatic motivation to eat is crucial for
potential therapeutic interventions. The core components of the forebrain network underlying cue-induced
feeding have been identified and include the basolateral area of the amygdala (BLA), the lateral hypothalamus
and orexin/hypocretin (ORX) neurons, and the ventromedial prefrontal cortex (vmPFC). Much remains
unknown about the temporal functional connectivity within this network and it is critical to determine which
specific circuit and neurotransmitter system is the controller of food motivation at test. The proposed studies
will utilize cutting-edge chemogenetic methods, DREADDs and Daun02 inactivation, and precise
neuroanatomical and neurochemical techniques to establish a novel vmPFC circuitry with the anterior
paraventricular nucleus of the thalamus (PVTa) and ORX receptor 1 signaling is the key controller—an on/off
switch within the network—for cognitive food motivation (Aim 1 & 2). Another goal is to determine if this
integrative function is mediated by the vmPFC neuronal ensemble plasticity, through dynamic communications
with the BLA and PVTa (Aim 3). These mechanisms will be interrogated in behavioral preparations for cue-
induced consumption (Aim 1) and persistent food seeking (context-mediated renewal of extinguished
responding to food cues; Aim 2) in male and female rats. Sex differences in context renewal of food seeking
were recently established and experiments here will test whether the vmPFC and PVTa are sites of sex-
specific regulation via connections with the ventral hippocampal formation. The findings from these studies will
establish key neurotransmitter and circuitry me...

## Key facts

- **NIH application ID:** 9873016
- **Project number:** 5R01DK085721-09
- **Recipient organization:** BOSTON COLLEGE
- **Principal Investigator:** Gorica D Petrovich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,510
- **Award type:** 5
- **Project period:** 2010-06-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873016

## Citation

> US National Institutes of Health, RePORTER application 9873016, Forebrain Circuits and Control of Feeding Behavior by Learned Cues (5R01DK085721-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873016. Licensed CC0.

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