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Abstract Flies have an open circulatory system and their Blood Brain Barrier (BBB) surrounds the brain like a tight cap. The fly BBB consists of two layers of glial cells. The outer layer is formed by the Perineurial Glia (PG). The inner BBB layer consists of the Subperineurial Glia (SPG) that form the tight barrier that, like its mammalian counterpart, acts both as a diffusion and a xenobiotic transport barrier. Underneath the SPG lie the neuronal cell bodies. The Drosophila BBB shows the same barrier properties as the mammalian barrier and profiling of Drosophila BBB cells has shown a high degree of molecular conservation. We have previously shown that the Drosophila BBB plays a sex-specific role in regulating behavior. Conditional adult feminization of SPG cells in otherwise normal males leads to significantly reduced courtship. In agreement with this, in a microarray screen of isolated SPG cells, we identified a number of male-enriched transcripts. One of them encodes the dopamine-2 like receptor (D2R). We have found that conditional knockdown of D2R in adult male Drosophila SPG decreases courtship. Likewise, D2R mutant males have courtship defects. They can be rescued by expression of wildtype D2R in the SPG cells of mature adult males, demonstrating a physiological requirement for the receptor in these cells for courtship control4. The D2R receptor is highly conserved. It has been found that it can act via biased signaling (through G protein or b-arrestin) in mammals. We have previously found that signaling through Gao and arrestin in the BBB is required for proper male courtship. Although D2R is best known for signaling through cAMP, we have not found a requirement for cAMP/PKA signaling for courtship. To investigate the signaling pathways downstream of D2R that are responsible for courtship control we have mutagenized D2R proteins and examined their ability to rescue D2R mutants. Based on Peterson et al. we designed proteins capable of G-protein or arrestin biased signaling, respectively, and tested their ability to rescue the courtship defects of D2R mutants. Our data suggest that D2R signaling through b-arrestin is a major mediator of BBB courtship control. 

Abstract The blood brain barrier (BBB) has the essential function to protect the brain from potentially hazardous molecules while also enabling controlled selective uptake. How these processes and signaling inside BBB cells control neuronal function is an intense area of interest. Signaling in the adultDrosophilaBBB is required for normal male courtship behavior and relies on male‐specific molecules in the BBB. Here we show that the dopamine receptorD2Ris expressed in the BBB and is required in mature males for normal mating behavior. Conditional adult male knockdown ofD2Rin BBB cells causes courtship defects. The courtship defects observed in geneticD2Rmutants can be rescued by expression of normalD2Rspecifically in the BBB of adult males.DrosophilaBBB cells are glial cells. Our findings thus identify a specific glial function for theDR2receptor and dopamine signaling in the regulation of a complex behavior.