A gαq signaling pathway in dopaminergic neurons suppresses memory

Which experiences persist as memories is a fundamental question in neurobiology. The balance between memory persistence and suppression is thought to be optimal for an organism to adapt to the ever-changing environment. Memory suppression is a process by which the brain limits the strength and expression of memories. Memory suppressors are genes whose disruption can enhance memory at different stages: acquisition, consolidation, forgetting, or recall. Here, using aversive classical conditioning in Drosophila, we show that Gαq acts as a memory suppressor in PPL1 dopaminergic neurons. Knockdown of gαq in dopaminergic neurons enhances acquisition, strengthens anesthesia-resistant memory, and impairs reversal learning. In vivo functional imaging revealed that gαq knockdown amplifies shock-evoked responses in a type of PPL1 neuron. Additionally, using ex vivo imaging and pharmacological experiments, we reveal that both Gαq and the OAMB receptor alter octopamine-evoked ER calcium responses in PPL1 neurons. Our results uncover a new role of Gαq signaling within dopaminergic neurons that suppresses memory.