Poster abstracts

Poster number 36 submitted by Sarah Light

δ-protocadherins: Organizers of neural circuit assembly

Sarah Light (Neuroscience Graduate Program), Michelle Emond (Neuroscience Department, The Ohio State University), James Jontes (Neuroscience Department, The Ohio State University)

Abstract:
Protocadherins (pcdhs) belong to a diverse family of cell adhesion molecules that are involved in a variety of developmental processes including neurogenesis, axon outgrowth, and arborization. Mutations in pcdhs are associated with neurodevelopmental defects including autism spectrum disorders, schizophrenia, and epilepsy. In particular, Pcdh19 is the second most clinically relevant gene in epilepsy, accounting for an estimated 16% of all epileptic encephalopathy cases. Our lab has previously shown that Pcdh19 is expressed in neuronal columns in the zebrafish optic tectum that originate from single progenitors. Zebrafish with Pcdh19 mutations display defects in columnar architecture and impairments in visually guided behaviors. To further explore the impact of Pcdh19 loss on neural function, we performed in vivo whole-brain calcium imaging to investigate the development of local circuits and evolution of neuronal activity patterns. Pcdh19 mutant larvae display significant differences in patterns of bursting activity, evolution of network correlation, and small world local clustering. These results suggest that the overall neuronal architecture and connectivity patterns of Pcdh19 mutants is altered, causing changes in global network dynamics. This work has given us insight into the functional output of the Pcdh19 mutant brain at the network level that may underlie the functional deficits previously described. Additionally, this project has produced a robust tool to characterize network dynamics and investigate alterations in brain development in vivo. In ongoing work, we are investigating intracellular binding partners of Pcdh19 involved in regulation of neurogenesis and axon outgrowth in the context of circuit assembly that may be contributing to the observed phenotype. Our long-term goals are to determine the molecular and cellular mechanisms of Pcdh19 during development in order to better understand how their loss of function leads to disease.

Keywords: neural development, calcium imagaing, protocadherins