Harnessing sensory food circuits to influence feeding behavior

PROJECT SUMMARY
Our modern food environment, with its widespread availability of energy-dense, palatable foods and associated
cues, is thought to interact with our physiology to promote food intake. This has contributed to the drastic increase
in obesity in the United States over the past several decades. However, most pharmacological weight loss
strategies target satiation pathways, not sensory pathways, and therefore may be less effective at eliminating
effects of environmental/sensory cues on food intake. Here we propose to take a novel approach to
understanding the drive to eat by examining the neural integration of sensory and nutritive food signals. First,
we will create sensory “engrams” – functional maps of neurons activated by discrete sensory stimuli – and
determine how activating or inhibiting these circuits can influence food preference. This process will reveal the
power of leveraging “neural tastes,” “neural smells,” and “neural nutrients” – sensory experiences without
external sensory input – to shift feeding behavior. Next, we will monitor neural activity in awake, freely moving
mice to determine how neural activity in response to the sensory properties of food relates to individual
differences in feeding behavior and future weight gain. Finally, we will monitor calcium dynamics in individual
neurons to reveal the activity patterns that integrate sensory and nutritive information in the brain across different
body weights. Successful implementation of this proposal has the potential to enable an entirely new line of
research and development for weight loss therapeutics that targets neural circuits that integrate sensory and
nutritive properties of food. My track record of scientific innovation and productivity, combined with the
collaborative environment at the Monell Chemical Senses Center and Department of Neuroscience at the
University of Pennsylvania, makes me uniquely suited to bridge the fields of chemosensory biology, feeding
neurobiology, and obesity to execute a project of this ambition. Overall, this NIH Director’s New Innovator Award
would launch my early career and provide the intellectual space to pursue innovative research that can redefine
the neural mechanisms that underlie overeating and obesity.

Grant Number: 4DP2AT011965-02
NIH Institute/Center: NIH
Principal Investigator: Amber Alhadeff