Enteroendocrine cell types that drive food reward and aversion
- University of California, San Francisco, United States
- Howard Hughes Medical Institute, University of California, San Francisco, United States
Abstract
Animals must learn through experience which foods are nutritious and should be consumed, and which are toxic and should be avoided. Enteroendocrine cells (EECs) are the principal chemosensors in the GI tract, but investigation of their role in behavior has been limited by the difficulty of selectively targeting these cells in vivo. Here we describe an intersectional genetic approach for manipulating EEC subtypes in behaving mice. We show that multiple EEC subtypes inhibit food intake but have different effects on learning. Conditioned flavor preference is driven by release of cholecystokinin whereas conditioned taste aversion is mediated by serotonin and substance P. These positive and negative valence signals are transmitted by vagal and spinal afferents, respectively. These findings establish a cellular basis for how chemosensing in the gut drives learning about food.
Data availability
Source data is included in the manuscript. RNA-seq data is available from the Gene Expression Omnibus (GSE203200). Villin-Flp mice have been deposited at Jackson laboratory.
-
Enteroendocrine cell types that drive food reward and aversionNCBI Gene Expression Omnibus, GSE203200.
-
Identification of functional enteroendocrine regulators by real-time single-cell differentiation mappingNCBI Gene Expression Omnibus, GSE113561.
Article and author information
Author details
Sheyda Mesgarzadeh
Funding
National Institutes of Health (R01-DK106399)
- Zachary A Knight
National Institutes of Health (RF1-NS116626)
- Zachary A Knight
Howard Hughes Medical Institute (Investigator)
- Zachary A Knight
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental protocols were approved by the University of California, San Francisco IACUC (protocol #AN179674) following the National Institutes of Health guidelines for the Care and Use of Laboratory Animals.
Copyright
© 2022, Bai et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 6,040
- views
-
- 1,263
- downloads
-
- 29
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Enteroendocrine cell types that drive food reward and aversion
eLife 11:e74964.
https://doi.org/10.7554/eLife.74964
Further reading
-
- Neuroscience
By influencing calcium homeostasis, local protein synthesis and the endoplasmic reticulum, a small protein called Rab10 emerges as a crucial cytoplasmic regulator of neuropeptide secretion.
-
- Neuroscience
The infralimbic cortex (IL) is essential for flexible behavioral responses to threatening environmental events. Reactive behaviors such as freezing or flight are adaptive in some contexts, but in others a strategic avoidance behavior may be more advantageous. IL has been implicated in avoidance, but the contribution of distinct IL neural subtypes with differing molecular identities and wiring patterns is poorly understood. Here, we study IL parvalbumin (PV) interneurons in mice as they engage in active avoidance behavior, a behavior in which mice must suppress freezing in order to move to safety. We find that activity in inhibitory PV neurons increases during movement to avoid the shock in this behavioral paradigm, and that PV activity during movement emerges after mice have experienced a single shock, prior to learning avoidance. PV neural activity does not change during movement toward cued rewards or during general locomotion in the open field, behavioral paradigms where freezing does not need to be suppressed to enable movement. Optogenetic suppression of PV neurons increases the duration of freezing and delays the onset of avoidance behavior, but does not affect movement toward rewards or general locomotion. These data provide evidence that IL PV neurons support strategic avoidance behavior by suppressing freezing.
