A pair of dopaminergic neurons DAN-c1 mediate Drosophila larval aversive olfactory learning through D2-like receptors

The intricate relationship between the dopaminergic system and olfactory
associative learning in Drosophila has been an intense scientific inquiry.
Leveraging the formidable genetic tools, we conducted a screening of 57
dopaminergic drivers, leading to the discovery of the DAN-c1 driver,
uniquely targeting a pair of dopaminergic neurons (DAN) in the larval
brain. While the involvement of excitatory D1-like receptors is
well-established, the role of D2-like receptors (D2Rs) remains
underexplored. Our investigation reveals the expression of D2Rs in both
DANs and the mushroom body (MB) of third instar larval brains. Silencing
D2Rs in DAN-c1 via microRNA disrupts aversive learning, further supported
by optogenetic activation of DAN-c1 during training, affirming the
inhibitory role of D2R autoreceptor. Intriguingly, D2R knockdown in the MB
impairs both appetitive and aversive learning. These findings elucidate
the distinct contributions of D2Rs in diverse brain structures, providing
novel insights into the molecular mechanisms governing associative
learning in Drosophila larvae.