The Role of the Drosophila Dopamine 2-Like Receptor in the Blood-Brain Barrier for Male Courtship Behavior

Courtship in Drosophila Melanogaster is an extensively studied and well characterized complex innate behavior with known molecular determinants. We have previously shown that the G-protein Go-alpha and sex-specific signaling in the Blood-Brain Barrier (BBB) influence male innate courtship sustainment towards naïve females. Here we show that the glial cells that form the BBB modulate male courtship behavior through the dopamine receptor D2R. The subperineurial glia cells (SPG) form the BBB by providing a contiguous barrier, connected by septate junctions, at the interface between the hemolymph and the brain. While the neural circuits required to produce scripted actions in the fly, such as the steps for courtship, have been widely investigated, much less is known about how the circuitry and functions underlying the fly behavior is influenced by cell- non-autonomous molecular processes. We have previously shown that male-specific molecules in the BBB regulate male courtship. We identified the Dopamine-2 like receptor (D2R) RNA as one of a number of sex-specifically enriched BBB transcripts. D2R knockdown with RNAi or over-expression of D2R with a transgene in the SPG of adult males significantly reduces courtship. Knockdown or overexpression of D2R with ubiquitous neuronal drivers or SPG knockdown specifically during development has no effect on the courtship index. D2R mutant flies have courtship defects that can be rescued by expression of wildtype D2R in the BBB of adult males. D2R likely signals through Go and beta-arrestin, to maintain full male courtship levels. Our results indicate an expanded role for dopamine signaling in the glial cells that surround the brain and provide a critical time frame for its action in behavior.