Journal
NATURE
Volume 592, Issue 7853, Pages 262-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03299-4
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Funding
- National Institutes of Health [R01 DC013289]
- Uehara Memorial Foundation
- Mishima Kaiun Memorial Foundation
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This study reveals a neuronal mechanism by which hunger selectively enhances attraction to food odors over other olfactory cues. Specifically, activation of hypothalamic AGRP neurons promotes food odor preference, which is mediated by neuropeptide Y release in the thalamus.
Internal state controls olfaction through poorly understood mechanisms. Odours that represent food, mates, competitors and predators activate parallel neural circuits that may be flexibly shaped by physiological need to alter behavioural outcome(1). Here we identify a neuronal mechanism by which hunger selectively promotes attraction to food odours over other olfactory cues. Optogenetic activation of hypothalamic agouti-related peptide (AGRP) neurons enhances attraction to food odours but not to pheromones, and branch-specific activation and inhibition reveal a key role for projections to the paraventricularthalamus. Mice that lack neuropeptide Y (NPY) or NPY receptor type 5 (NPY5R) fail toprefer food odours over pheromones after fasting, and hunger-dependent food-odour attraction is restored by cell-specific NPY rescue in AGRP neurons. Furthermore, acute NPY injection immediately rescues food-odour preference without additional training, indicating that NPY is required for reading olfactory circuits during behavioural expression rather than writing olfactory circuits during odour learning. Together, these findings show that food-odour-responsive neurons comprise an olfactory subcircuit that listens to hunger state through thalamic NPY release, and more generally, provide mechanisticinsights into how internal state regulates behaviour.
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