# Olfactory inputs to appetite neurons in the hypothalamus

## TL;DR

This study reveals how different smell signals are processed by brain cells that control hunger and satiety.

## Contribution

The paper identifies distinct neural pathways linking the olfactory system to appetite-regulating neurons in the hypothalamus.

## Key findings

- AgRP and POMC neurons receive indirect input from different olfactory cortical areas.
- Upstream neurons relay olfactory signals to AgRP and POMC neurons in distinct ways.
- AgRP neurons show heterogeneous expression of neuromodulator receptors.

## Abstract

The sense of smell profoundly influences appetite, but the underlying neural circuits are unexplored. Here, we examine circuits upstream of hypothalamic agouti-related peptide (AgRP) neurons, which stimulate appetite, and pro-opiomelanocortin (POMC) neurons, which inhibit it. We find that AgRP and POMC neurons receive indirect input from different combinations of olfactory cortical areas and thus process different sets of olfactory signals. We also identify different complements of neurons more directly upstream of AgRP versus POMC neurons that could relay olfactory signals to them. RNA analyses reveal differential expression of neuromodulator receptors among AgRP neurons and cognate receptor ligands in upstream neurons in specific brain areas. These findings uncover multiple pathways for linking the sense of smell to hypothalamic appetite neurons.

The sense of smell has potent effects on appetite, but the underlying neural pathways remain undefined. Here, we investigated how olfactory signals reach two subsets of appetite-linked (“appetite”) neurons in the hypothalamic arcuate nucleus: Agouti-related peptide (AgRP) neurons, which stimulate appetite, and POMC (pro-opiomelanocortin) neurons, which suppress it. Using polysynaptic viral tracing, we show that AgRP and POMC neurons receive indirect input from partially overlapping but distinct areas of the olfactory cortex, indicating that they process different sets of olfactory information. We also identify different complements of neurons more directly upstream of AgRP and POMC neurons that could relay olfactory cortical signals to the appetite neurons. Single-cell transcriptomics shows heterogeneous expression of neuromodulator receptors among AgRP neurons, suggesting variations in the signals they receive. Integrated viral tracing and RNA localization further reveals selected brain areas where upstream neurons express cognate receptor ligands. Together, these findings outline multiple pathways by which distinct olfactory and modulatory signals are differentially routed to neurons that promote versus inhibit appetite.