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

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• G protein-coupled receptor 85 (GPR85), also known as SREB2, is a highly conserved seven-transmembrane receptor with an unknown biological function.
• Its expression patterns and specific roles throughout development and adulthood remain largely unexplored.

Purpose of the Study:

• To investigate the properties and functions of Gpr85 in zebrafish across different life stages.
• To determine the localization and impact of Gpr85 on neuronal activity and behavior.

Main Methods:

• Utilized a combination of genetic manipulation, in vivo imaging, transcriptomic analysis, electrophysiology, and behavioral assays in zebrafish.
• Generated a fluorochrome-tagged Gpr85 construct for in vivo localization studies.
• Performed transcriptomic profiling of cerebellar granule cells (GCs) and electrophysiological recordings.

Main Results:

• Demonstrated conserved expression of gpr85 in the central nervous system, retina, and intestine of zebrafish.
• Provided the first in vivo evidence of Gpr85 enrichment at synaptic sites in the brain and retina.
• Observed increased neuronal activity and heightened excitability in Gpr85-deficient GCs.
• Found that Gpr85 loss enhances light-triggered motor responses in larval zebrafish.

Conclusions:

• Gpr85 functions as a synapse-enriched modulator of neuronal excitability.
• Gpr85 plays a role in sensory-driven behavior, influencing motor responses.
• These findings offer novel insights into the biological roles of GPR85.