Optimization of Cognitive Behavioral Tasks for CLOCKΔ19 mouse model of Bipolar Disorder

Poster Session A - Saturday, April 13, 2024, 2:30 – 4:30 pm EDT, Sheraton Hall ABC

Eden Fraatz¹ (efraatz570@g.rwu.edu), Simrat Dhillon¹, Dennis Arruda¹, Giana Guerra¹, Brittany Martin¹, Samantha Soares¹, Victoria Heimer-McGinn¹; ¹Roger Williams University

Cognitive deficits are a trait symptom of bipolar disorder (BD) and are predictive of disease outcome and quality of life. However, they remain understudied and undertreated, largely due to difficulties developing animal models that reproduce the mood fluctuations that characterize BD. One emerging model is the ClockΔ19 transgenic mouse line, which exhibits regular mood cycling between manic and euthymic behavior over 24 hours. In this study, we (1) corroborate the known phenotypic characteristics of ClockΔ19 and (2) tailor cognitive behavioral tasks for the model using male and female wildtype and homozygous mice. For the first goal, an open field maze (OFM) evaluating locomotion revealed that both male and female ClockΔ19 mice display increased hyperactivity. For the second goal, we used novel object recognition (NOR), novel object location (NOL), and attentional set shifting (AST) tasks. In AST, we observed enhanced discrimination in ClockΔ19 mice accompanied by shorter latencies. Since AST uses food rewards with high sugar content, and the ClockΔ19 model displays increased reward-seeking behavior, we piloted the use of natural food rewards. We find that modifying the food reward increases latency times while maintaining performance levels. In NOR/NOL, we observe trends toward impairments that mirror the human population. However, we have had to modify specific object pairings and layouts that are better suited for this model. Our results will validate the use of these cognitive tasks with the ClockΔ19 mouse, which will help us validate the ClockΔ19 mouse for use in translational studies of cognitive function in BD.

Topic Area: METHODS: Other