Abstract
GPR85/SREB2 is an exceptionally well-conserved orphan 7TM receptor with unclear biological attributes. In this study, we used several zebrafish genetic models to investigate Gpr85 properties and functions throughout development and adulthood. We describe that, like in mammals, gpr85 is expressed by various neuronal populations throughout zebrafish development and adulthood in the central nervous system, retina and intestine. The overexpression of a fluorochrome-tagged version of the receptor in gpr85-expressing neurons provides the first in vivo evidence that Gpr85 is enriched at the synaptic level in the brain and retina. Transcriptomic analysis of Gpr85 knock-out zebrafish cerebellar granule cells revealed changes in gene expression related to enhanced neuronal activity. Further investigations using ex vivo cerebellar slices demonstrate that the electrophysiological activity of Gpr85 deficient granule cells are increased. We also observed that Gpr85 deficient larvae exhibit enhanced light-triggered startle responses in dark/light paradigm behavioral experiments. Altogether, our results provide evidence that, in zebrafish, Gpr85 is enriched at the synaptic level in vivo and influences granule cell electrophysiological properties as well as light-triggered motor responses.
Competing Interest Statement
The authors have declared no competing interest.