Associative learning disrupted by impaired G_s signaling in Drosophila mushroom bodies

Disruptions in mushroom body (MB) or central complex (CC) brain structures impair Drosophila associative olfactory learning. Perturbations in adenosine 3′,5′ monophosphate signaling also disrupt learning. To integrate these observations, expression of a constitutively activated stimulatory heterotrimeric guanosine triphosphate-binding protein α subunit (Gα_s*) was targeted to these brain structures. The ability to associate odors with electroshock was abolished when Gα_s* was targeted to MB, but not CC, structures, whereas sensorimotor responses to these stimuli remained normal. Expression of Gα_s* did not affect gross MB morphology, and wild-type Gα_s expression did not affect learning. Thus, olfactory learning depends on regulated G_s signaling in Drosophila MBs.