Behavioral analysis through the lifespan of disc1 mutant zebrafish identifies defects in sensorimotor transformation
Brock R. Pluimer,
Devin L. Harrison,
Chanon Boonyavairoje,
Eric P. Prinssen,
Mark Rogers-Evans,
Randall T. Peterson,
Summer B. Thyme,
Anjali K. Nath
Affiliations
Brock R. Pluimer
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA
Devin L. Harrison
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA
Chanon Boonyavairoje
Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Eric P. Prinssen
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Grenzacherstrasse 124, 4070 Basel, Switzerland
Mark Rogers-Evans
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Grenzacherstrasse 124, 4070 Basel, Switzerland
Randall T. Peterson
Deparment of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA
Summer B. Thyme
Department of Neurobiology, University of Alabama, Birmingham, AL 35294, USA
Anjali K. Nath
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Corresponding author
Summary: DISC1 is a genetic risk factor for multiple psychiatric disorders. Compared to the dozens of murine Disc1 models, there is a paucity of zebrafish disc1 models—an organism amenable to high-throughput experimentation. We conducted the longitudinal neurobehavioral analysis of disc1 mutant zebrafish across key stages of life. During early developmental stages, disc1 mutants exhibited abrogated behavioral responses to sensory stimuli across multiple testing platforms. Moreover, during exposure to an acoustic sensory stimulus, loss of disc1 resulted in the abnormal activation of neurons in the pallium, cerebellum, and tectum—anatomical sites involved in the integration of sensory perception and motor control. In adulthood, disc1 mutants exhibited sexually dimorphic reduction in anxiogenic behavior in novel paradigms. Together, these findings implicate disc1 in sensorimotor processes and the genesis of anxiogenic behaviors, which could be exploited for the development of novel treatments in addition to investigating the biology of sensorimotor transformation in the context of disc1 deletion.
