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δ2-Protocadherins organize parallel indirect basal ganglia circuits
Biorxiv : the Preprint Server for Biology
|December 22, 2025
Summary
Two protocadherins, PCDH17 and PCDH10, organize distinct basal ganglia circuits. These circuits control different behaviors, with PCDH17 influencing task learning and PCDH10 affecting sensorimotor habituation.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The basal ganglia (BG) comprise parallel neural circuits that regulate diverse behaviors.
- The molecular mechanisms underlying the organization of these distinct parallel BG circuits remain largely unknown.
Purpose of the Study:
- To investigate the role of δ2-protocadherins (PCDHs) in organizing parallel indirect basal ganglia circuits.
- To identify the specific functions of PCDH17 and PCDH10 in behavior regulation.
Main Methods:
- Utilized conditional knockout (cKO) mouse models for Pcdh17 and Pcdh10 in indirect pathway-specific neurons.
- Analyzed the anatomical and functional consequences of Pcdh gene deletion on BG circuit formation and behavior.
Main Results:
- PCDH17 and PCDH10 exhibit complementary expression patterns in the BG, defining two distinct indirect BG connections.
- Pcdh17-cKO mice displayed impaired task learning, while Pcdh10-cKO mice showed deficits in motor/sensory habituation.
- Conditional knockouts resulted in region-preferential impairment of indirect BG circuit establishment.
Conclusions:
- PCDH17 and PCDH10 act as molecular organizers for distinct indirect BG circuits.
- These findings elucidate the molecular basis for parallel BG circuit organization and their specific behavioral outputs.
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