PUBLICATION
Synaptic Gpr85 influences cerebellar granule cells electrical properties and light-induced behavior in zebrafish
- Authors
- Darche-Gabinaud, R., Kaafarani, A., Chazalon, M., Suain, V., Hendrickx, E., Conrard, L., Lefort, A., Libert, F., Demirler, M.C., Schiffmann, S.N., Perez-Morga, D., Wittamer, V., Parmentier, M., Pirson, I.
- ID
- ZDB-PUB-251111-7
- Date
- 2025
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience : (Journal)
- Registered Authors
- Pirson, Isabelle, Wittamer, Valerie
- Keywords
- none
- MeSH Terms
-
- Cerebellum*/cytology
- Cerebellum*/physiology
- Neurons*/physiology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Zebrafish Proteins*/physiology
- Animals, Genetically Modified
- Synapses*/metabolism
- Synapses*/physiology
- Light
- Animals
- Zebrafish
- Behavior, Animal*/physiology
- Receptors, G-Protein-Coupled*/genetics
- Receptors, G-Protein-Coupled*/physiology
- PubMed
- 41213803 Full text @ J. Neurosci.
Citation
Darche-Gabinaud, R., Kaafarani, A., Chazalon, M., Suain, V., Hendrickx, E., Conrard, L., Lefort, A., Libert, F., Demirler, M.C., Schiffmann, S.N., Perez-Morga, D., Wittamer, V., Parmentier, M., Pirson, I. (2025) Synaptic Gpr85 influences cerebellar granule cells electrical properties and light-induced behavior in zebrafish. The Journal of neuroscience : the official journal of the Society for Neuroscience. :.
Abstract
GPR85/SREB2 is an exceptionally conserved orphan seven-transmembrane receptor with poorly understood biological function. Here, we combine genetic, imaging, transcriptomic, electrophysiological, and behavioral approaches in zebrafish to uncover the properties and roles of Gpr85 across development and adulthood. We show that, as in mammals, gpr85 is expressed in diverse neuronal populations within the central nervous system, retina and intestine. Using a fluorochrome-tagged Gpr85 construct expressed in native domains, we provide the first in vivo evidence that Gpr85 is enriched at synaptic sites in both the brain and retina. Transcriptomic profiling of cerebellar granule cells lacking Gpr85 reveals gene expression changes consistent with increased neuronal activity. Electrophysiological recordings from cerebellar slices confirm that Gpr85-deficient granule cells exhibit heightened excitability. Functionally, Gpr85 loss enhances light-triggered motor responses in larval zebrafish. Together, these findings position Gpr85 as a synapse-enriched modulator of neuronal excitability and sensory-driven behavior, offering new insight into its roles.Significance Statement GPR85 is a highly conserved orphan GPCR with strong enrichment in the central nervous system, yet its physiological roles remain poorly understood. Here we show that Gpr85 modulates neuronal activity and light-induced behavior in zebrafish. Confocal and electron microscopy show that Gpr85 localizes to synaptic compartments throughout development and adulthood. scRNA sequencing and innovative electrophysiological recordings of cerebellar granule cells ex vivo reveal that Gpr85 impacts granule cell electrical properties. Loss of Gpr85 leads to enhanced stimuli-induced motor response in larvae. Given its remarkable evolutionary conservation and its association with psychiatric traits in human studies, our findings offer insights into the molecular mechanisms that shape neuronal excitability and behavior across species.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping