Digital phenotyping and electrophysiology in mice – UROP Spring Symposium 2021

Digital phenotyping and electrophysiology in mice

Deniz Kirca

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Pronouns: He/Him/His

Research Mentor(s): Brendon Watson, Assistant Professor
Research Mentor School/College/Department: Psychiatry, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 6 (4pm-4:50pm)
Breakout Room: Room 11
Presenter: 5

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Abstract

The molecular, synaptic, and neuromodulatory variations in a variety of brain regions, namely the the prefrontal cortex, nucleus accumbens, and the ventral hippocampus1, have been associated with changes in behavior quantified by metrics such as the Forced Swim Test (FST)2, Sucrose Preference Test3, and the Open Field Test4. While the behavior of mice exposed to chronic stress has been extensively studied, there is a need for more information regarding the behavior of these mice over a longer span of time. Additionally, due to the difficulty of recording electrical activity for extended periods of time in specific regions of the brain, there are few studies that analyze the longitudinal alterations in electrophysiology that may be correlated with exposure to chronic stress. In order to address both of these outstanding questions in stress research, the Watson Lab has designed a system, called the Digital Homecage, that is capable of measuring over 50 behavioral metrics in mice and of recording electrophysiology recordings from multiple brain regions at once, continuously for multiple weeks at a time. The purpose of this study is to use the novel abilities provided by the Digital Homecage to test the longitudinal effects of chronic stress on the behavior and neurobiology of mice. As part of this study, mice will have 6 electroencephalography (EEG) electrodes implanted into their brains, and, after acclimatization to the digital homecage and a two-week baseline recording period, the experimental group of mice will be exposed to chronic stress using the Chronic Unpredictable Stress (CUS) paradigm. At the conclusion of the experiment, the behavior and electrophysiological activity of these mice will be analyzed to test our hypotheses: a.) that CUS induces consistent changes across multiple dimensions of behavior and physiology in a specific temporal sequence, and b.) that the Electrophysiologic Background State (EBS) will be altered by CUS, specifically that Spike Rate Variance (SRV) will decrease and that Excitatory-Inhibitory Balance (EIB) will increase. This study will not only provide valuable data on the longitudinal effects of chronic stress, but will also advance the practice of behavioral phenotyping in mice through the innovations of the Digital Homecage. References [1] Campioni, M. R., Xu, M., & McGehee, D. S. (2009). Stress-induced changes in nucleus accumbens glutamate synaptic plasticity. Journal of Neurophysiology, 101(6), 3192-3198. doi:10.1152/jn.91111.2008 [2] Fitzgerald, P., Yen, J., & Watson, B. (2019). Stress-sensitive Antidepressant-Like effects of ketamine in the mouse forced swim test. PLOS One, 85(10). doi:10.1016/j.biopsych.2019.03.886 [3] Eagle, A., Mazei-Robison, M., & Robison, A. (2016). Sucrose preference test to measure stress-induced anhedonia. Nature Protocols, 6(11). doi:10.21769/bioprotoc.1822 [4] Seibenhener, M. L., & Wooten, M. C. (2015). Use of the open field maze to measure locomotor and anxiety-like behavior in mice. Journal of Visualized Experiments, (96). doi:10.3791/52434

Authors: Brendon Watson
Research Method: Laboratory Research

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