PT  - JOURNAL ARTICLE
AU  - Manxiu Ma
AU  - Alexandro D. Ramirez
AU  - Tong Wang
AU  - Rachel L. Roberts
AU  - Katherine E. Harmon
AU  - David Schoppik
AU  - Avirale Sharma
AU  - Christopher Kuang
AU  - Stephanie L. Goei
AU  - James A. Gagnon
AU  - Steve Zimmerman
AU  - Shengdar Q. Tsai
AU  - Deepak Reyon
AU  - J. Keith Joung
AU  - Emre R. F. Aksay
AU  - Alexander F. Schier
AU  - Y. Albert Pan
TI  - Zebrafish <em>Dscaml1</em> is Essential for Retinal Patterning and Function of Oculomotor Subcircuits
AID  - 10.1101/658161
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 658161
4099  - http://biorxiv.org/content/early/2019/06/03/658161.short
4100  - http://biorxiv.org/content/early/2019/06/03/658161.full
AB  - Down Syndrome Cell Adhesion Molecules (dscam and dscaml1) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the role of dscaml1 in the zebrafish oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Loss of zebrafish dscaml1 resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses showed that mutants have abnormal gaze stabilization, impaired fixation, disconjugation, and faster fatigue. Notably, the saccade and fatigue phenotypes in dscaml1 mutants are reminiscent of human ocular motor apraxia, for which no animal model exists. Two-photon calcium imaging showed that loss of dscaml1 leads to impairment in the saccadic premotor pathway but not the pretectum-vestibular premotor pathway, indicating a subcircuit requirement for dscaml1. Together, we show that dscaml1 has both broad and specific roles in oculomotor circuit function, providing a new animal model to investigate the development of premotor pathways and their associated human ocular disorders.