PUBLICATION

Multiplane calcium imaging reveals disrupted development of network topology in zebrafish pcdh19 mutants

Authors
Light, S.E.W., Jontes, J.D.
ID
ZDB-PUB-190508-3
Date
2019
Source
eNeuro   6(3): (Journal)
Registered Authors
Jontes, James
Keywords
calcium imaging, functional connectomics, pcdh19, zebrafish
MeSH Terms
  • Animals
  • Brain/growth & development*
  • Cadherins/genetics
  • Cadherins/physiology*
  • Calcium Signaling*
  • Image Processing, Computer-Assisted
  • Neural Pathways/physiology
  • Optical Imaging
  • Signal Processing, Computer-Assisted
  • Zebrafish/growth & development*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed
31061071 Full text @ eNeuro
Abstract
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.Significance Statement Non-clustered protocadherins are linked to neurodevelopmental disorders that include microcephaly, intellectual disability, autism spectrum disorders and epilepsy. In humans, mutations in PCDH19 cause a female limited form of infantile epileptic encephalopathy and are associated with an increased incidence of schizophrenia and autism. In this study, we use large-scale calcium imaging to reveal that mutations in zebrafish pcdh19 alter the development of brain network topology. This work is the first to use functional imaging to explore the effects of a clinically relevant mutation on brain-wide network assembly in vivo We show that graph analysis of spontaneous network activity is a sensitive method for revealing subtle changes to network architecture in response to genetic perturbations.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping