Nicotinic receptor in dopamine neurons mediates learned odor choice

Nicotinic acetylcholine signaling modulates dopaminergic output in mammalian midbrain circuits and can thereby influence decision-making. In Drosophila, dopamine neurons (DANs) in the protocerebral anterior medial (PAM) cluster convey sugar reward signals and promote approach toward a rewarded odor after associative learning. Although nicotinic acetylcholine receptors (nAChRs) have been implicated in regulating PAM DAN excitability and transmitter release, how this modulation supports specific cognitive operations during learning and memory remains unclear. Here, we tested the role of nAChRs in PAM DANs in odor-sugar associative learning and memory. Among nine nAChR genes examined, loss of the nicotinic acetylcholine receptor α1 subunit (Dα1) in PAM neurons impaired appetitive memory. Consistent with this requirement, Dα1 was detected in these DANs at both the transcript and protein levels, with Dα1 puncta observed in PAM axon-terminal and putative dendritic regions. Importantly, live imaging showed that Dα1 knockdown in PAM DANs attenuated odor-evoked synaptic Caa2+ signals, whereas sugar-evoked Ca2+ responses were largely preserved. Behaviorally, Dα1 knockdown in PAM DANs reduced performance in a two-odor forced-choice discrimination task, whereas no performance deficit was detected across the single-odor pursuit conditions or innate odor choice. Together, these results identify a nicotinic mechanism in PAM DANs that supports odor-evoked synaptic activity and contributes to learned odor-choice performance when competing odor cues are present.