Synaptic Gpr85 Influences Cerebellar-Granule-Cell Electrical Properties and Light-Induced Behavior in Zebrafish

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 (GCs) lacking Gpr85 reveals gene expression changes consistent with increased neuronal activity. Electrophysiological recordings from cerebellar slices confirm that Gpr85-deficient GCs 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.

• Publication year

  2025

• Venue

  Journal of Neuroscience

• Publication date

  2025-11-10

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.0770-25.2025PMID 41213803PMCID PMC12696619
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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