A temporally restricted function of the dopamine receptor Dop1R2 during memory formation.

Dopamine is a crucial neuromodulator involved in many brain processes, including learning and the formation of memories. Dopamine acts through multiple receptors and controls an intricate signaling network to regulate different tasks. While the diverse functions of dopamine are intensely studied, the interplay and role of the distinct dopamine receptors to regulate different processes is less well understood. An interesting candidate is the dopamine receptor Dop1R2 (also known as Damb), as it could connect to different downstream pathways. Dop1R2 is reported to be involved in forgetting and memory maintenance; however, the circuits requiring the receptors are unknown. To study Dop1R2 and its role in specific spatial and temporal contexts, we generated a conditional knockout line using the CRISPR-Cas9 technique. Two FRT sites were inserted, allowing flippase-mediated excision of the dopamine receptor in neurons of interest. To study the function of Dop1R2, we knocked it out conditionally in the mushroom body of Drosophila melanogaster, a well-studied brain region for memory formation. We show that Dop1R2 is required for later memory forms but not for short-term aversive or appetitive memories. Moreover, Dop1R2 is specifically required in the α/β-lobe and the α'/β'-lobe but not in the γ-lobe of the mushroom body. Our findings show a spatially and temporally restricted role of Dop1R2 in the process of memory formation, highlighting the differential requirement of receptors during distinct phases of learning.