# Hungry for Knowledge: Octopamine Signaling Regulates Hunger‐Enhanced Olfactory Learning

## TL;DR

Hunger improves learning about food smells in worms, using a chemical called octopamine, and similar effects are seen in mice with a related chemical.

## Contribution

Discovery of two octopamine signaling pathways in C. elegans and a conserved norepinephrine pathway in mice for hunger-enhanced olfactory learning.

## Key findings

- Hunger enhances both aversive and appetitive olfactory learning in C. elegans.
- Octopamine signaling through RIC interneuron activates ASH and AIY neurons for memory formation.
- Norepinephrine and alpha1-adrenergic receptors may mediate similar effects in mice.

## Abstract

Hunger, a state of nutrient deficiency, significantly enhances cognitive behaviors by heightening sensitivity to food‐related stimuli. However, the mechanisms by which hunger influences olfactory learning remain unclear. In this study, it is shown that aversive or appetitive memory is formed faster in hungry C. elegans. These findings reveal that hunger‐induced octopamine release from the interneuron RIC enhances both aversive and appetitive olfactory learning. By analyzing neural circuits downstream of RIC, two distinct pathways involved in memory formation are identified. For aversive learning, the sensory neuron ASH is activated via the SER‐3 receptor, leading to glutamate release, which acts on the GLR‐2 receptor in AIA interneuron during the starvation phase. During the training section, AIA is subsequently inhibited via the glutamate‐gated chloride channel GLC‐3. In contrast, octopamine targets AIY interneurons through the SER‐6 receptor, promoting appetitive learning. Furthermore, it is indicated that norepinephrine, the mammalian homolog of octopamine, and alpha1‐adrenergic receptors may be involved in hunger‐enhanced olfactory learning in mice. These findings may offer insights into the neural mechanisms that underlie cognitive flexibility in response to physiological states.

Researchers demonstrate that hunger state facilitates both aversive and appetitive olfactory learning. Two distinct octopamine signaling pathways are involved in aversive or appetitive memory formation in the hunger state. And, hunger state also facilitates the formation of both types of memories via an evolutionarily conserved norepinephrine (the mammalian homolog of octopamine) signaling pathway in mice.