Multiplane Calcium Imaging Reveals Disrupted Development of Network Topology in Zebrafish pcdh19 Mutants

Functional brain networks self-assemble during development, although the molecular basis of network assembly is poorly understood. Protocadherin-19 (pcdh19) is a homophilic cell adhesion molecule that is linked to neurodevelopmental disorders, and influences multiple cellular and developmental events in zebrafish. Although loss of PCDH19 in humans and model organisms leads to functional deficits, the underlying network defects remain unknown. Here, we employ multiplane, resonant-scanning in vivo two-photon calcium imaging of developing zebrafish, and use graph theory to characterize the development of resting state functional networks in both wild-type and pcdh19 mutant larvae. We find that the brain networks of pcdh19 mutants display enhanced clustering and an altered developmental trajectory of network assembly. Our results show that functional imaging and network analysis in zebrafish larvae is an effective approach for characterizing the developmental impact of lesions in genes of clinical interest.