Mapping GPR88-Venus illuminates a novel role for GPR88 in sensory processing.

TitleMapping GPR88-Venus illuminates a novel role for GPR88 in sensory processing.
Publication TypeJournal Article
Year of Publication2018
AuthorsEhrlich AT, Semache M, Bailly J, Wojcik S, Arefin TM, Colley C, Le Gouill C, Gross F, Lukasheva V, Hogue M, Darcq E, Harsan L-A, Bouvier M, Kieffer BL
JournalBrain Struct Funct
Volume223
Issue3
Pagination1275-1296
Date Published2018 Apr
ISSN1863-2661
Abstract

GPR88 is an orphan G-protein coupled receptor originally characterized as a striatal-enriched transcript and is a potential target for neuropsychiatric disorders. At present, gene knockout studies in the mouse have essentially focused on striatal-related functions and a comprehensive knowledge of GPR88 protein distribution and function in the brain is still lacking. Here, we first created Gpr88-Venus knock-in mice expressing a functional fluorescent receptor to fine-map GPR88 localization in the brain. The receptor protein was detected in neuronal soma, fibers and primary cilia depending on the brain region, and remarkably, whole-brain mapping revealed a yet unreported layer-4 cortical lamination pattern specifically in sensory processing areas. The unique GPR88 barrel pattern in L4 of the somatosensory cortex appeared 3 days after birth and persisted into adulthood, suggesting a potential function for GPR88 in sensory integration. We next examined Gpr88 knockout mice for cortical structure and behavioral responses in sensory tasks. Magnetic resonance imaging of live mice revealed abnormally high fractional anisotropy, predominant in somatosensory cortex and caudate putamen, indicating significant microstructural alterations in these GPR88-enriched areas. Further, behavioral analysis showed delayed responses in somatosensory-, visual- and olfactory-dependent tasks, demonstrating a role for GPR88 in the integration rather than perception of sensory stimuli. In conclusion, our data show for the first time a prominent role for GPR88 in multisensory processing. Because sensory integration is disrupted in many psychiatric diseases, our study definitely positions GPR88 as a target to treat mental disorders perhaps via activity on cortical sensory networks.

DOI10.1007/s00429-017-1547-3
Alternate JournalBrain Struct Funct
PubMed ID29110094
PubMed Central IDPMC5871604
Grant ListMOP-10501 / / Canadian Institutes of Health Research / Canada
P50 DA005010 / DA / NIDA NIH HHS / United States
16658 / / National Institute on Alcohol Abuse and Alcoholism /
05010 / / National Institute on Drug Abuse /
U01 AA016658 / AA / NIAAA NIH HHS / United States