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Appetitive Associative Olfactory Learning in Drosophila Larvae
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Olfactory inputs to appetite neurons in the hypothalamus.

Donghui Kuang1, Naresh K Hanchate1, Chia-Ying Lee1

  • 1Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109.

Proceedings of the National Academy of Sciences of the United States of America
|January 27, 2026
PubMed
Summary

Smell influences appetite via distinct neural pathways. Researchers mapped how olfactory signals reach appetite-stimulating (AgRP) and appetite-suppressing (POMC) neurons in the hypothalamus, revealing complex routing.

Keywords:
appetitecircuitsolfactory

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Area of Science:

  • Neuroscience
  • Neuroendocrinology
  • Sensory Systems

Background:

  • The sense of smell profoundly impacts appetite regulation.
  • Neural circuits linking olfactory stimuli to appetite control remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the neural pathways conveying olfactory information to hypothalamic appetite-regulating neurons.
  • To differentiate olfactory signal processing by appetite-stimulating (AgRP) and appetite-suppressing (POMC) neurons.

Main Methods:

  • Polysynaptic viral tracing to map neural inputs.
  • Single-cell transcriptomics to analyze receptor expression.
  • Integrated viral tracing and RNA localization to identify ligand-receptor pairs.

Main Results:

  • AgRP and POMC neurons receive indirect olfactory input from distinct, partially overlapping olfactory cortical areas.
  • Different upstream neuronal populations were identified as potential relays for olfactory signals.
  • AgRP neurons exhibit heterogeneous neuromodulator receptor expression, suggesting varied signal reception.
  • Specific brain regions with upstream neurons expressing cognate receptor ligands were identified.

Conclusions:

  • Multiple, distinct neural pathways differentially route olfactory and modulatory signals to appetite-promoting and appetite-inhibiting neurons.
  • This provides a framework for understanding how smell influences feeding behavior.
  • Highlights the complexity of olfactory-driven appetite control in the hypothalamus.