Nicotinic Receptor in Dopamine Neurons Shapes Learned Odor Choice in Flies

A new study in PLOS Genetics identifies a specific nicotinic acetylcholine receptor subunit in fruit fly dopamine neurons as a key component of learned odor choice. The research, led by Nobuhiro Yamagata and Hiromu Tanimoto, shows that the Dα1 receptor subunit supports the synaptic activity of reward-signaling dopamine neurons when an animal must choose between competing odor cues.

In Drosophila, dopamine neurons of the protocerebral anterior medial (PAM) cluster convey sugar reward signals and, after associative learning, promote approach toward an odor that has been paired with sugar. While nicotinic acetylcholine receptors had previously been implicated in regulating the excitability and transmitter release of these neurons, how this modulation contributes to specific cognitive operations during learning and memory remained unclear.

The team examined nine nicotinic acetylcholine receptor genes and found that loss of the Dα1 subunit in PAM dopamine neurons impaired appetitive memory. Consistent with this requirement, the researchers detected Dα1 in these neurons at both the transcript and protein levels, with receptor puncta observed in the neurons’ axon-terminal and putative dendritic regions.

Live imaging provided a functional link: knocking down Dα1 in PAM dopamine neurons attenuated odor-evoked synaptic calcium signals, while sugar-evoked calcium responses were largely preserved. This dissociation suggests the receptor specifically supports the processing of odor information rather than the reward pathway itself.

Behavioral experiments sharpened the picture. Dα1 knockdown reduced performance in a two-odor forced-choice discrimination task, but no deficit appeared in single-odor pursuit conditions or in innate odor choice. The receptor therefore appears to matter specifically when learned preferences must guide a decision between competing odor cues.

Because nicotinic acetylcholine signaling modulates dopaminergic output in mammalian midbrain circuits and can influence decision-making, the findings offer a mechanistic parallel relevant beyond flies. The study identifies a nicotinic mechanism in reward-signaling dopamine neurons that supports odor-evoked synaptic activity and contributes to learned odor-choice performance, clarifying how cholinergic modulation can underpin a specific memory-guided behavior.

Subject of Research: The role of the nicotinic acetylcholine receptor subunit Dα1 in dopamine neurons during odor–sugar associative learning in fruit flies

Article Title: Nicotinic receptor in dopamine neurons mediates learned odor choice

Article References: Yamagata, N., Takahashi, N., Ichikawa, R., Wada, E., Murakami, M., Abe, A., Kanno, M., Ichinose, T., Katayama, N., & Tanimoto, H. (2026). Nicotinic receptor in dopamine neurons mediates learned odor choice. PLOS Genetics, 22(10), e1012356. https://doi.org/10.1371/journal.pgen.1012356

Image Credits: AI Generated

DOI: 10.1371/journal.pgen.1012356

Keywords: Drosophila, dopamine neurons, nicotinic acetylcholine receptor, associative learning, odor choice, appetitive memory, PAM cluster, calcium imaging, decision-making, PLOS Genetics, Nicotinic, receptor