Poster Title

Open-Source Alternatives to Investigate Affective and Autonomic Phenotypes in HD Model Mice

Co-Author(s)

Eva Vik, Wes Solem, Sam Legg, Dom Shuttleworth, Shawn Minnig, Robert Bragg, Jeff Cantle, Sydney Coffey, Jeff Carroll

Research Mentor(s)

Jeff Carroll

Affiliated Department

Psychology

Sort Order

53

Start Date

17-5-2017 1:00 PM

End Date

17-5-2017 12:00 PM

Document Type

Event

Abstract

Huntington's disease (HD) is a neurodegenerative disease classically characterized as a movement disorder, however non-classical symptoms have profound effects on the lives of HD mutation carriers. Apathy is one of the most prevalent psychiatric HD symptoms, is present in early stages, and continues to progress through all stages of the disease. Similarly, circadian dysfunction leads to sleep disturbances in HD patients, exacerbating symptoms and possibly contributing to disease progression. Despite this, current studies in HD mouse models largely focus on motor processes and rarely investigate the effects of these other crucial phenotypes, which may confound behavioral assays intending to measure cognitive, autonomic, and even motor symptoms. Commercial operant conditioning chambers used to assess affective phenotypes have several drawbacks, including high cost, low throughput and limited customizability. We adapted an open-source operant chamber that utilizes off-the-shelf hardware (Rodent Operant Bucket; Devarakonda et al., 2015) to investigate motivational phenotypes in an HD model mouse. HttQ111/+ and wild-type (Htt+/+) mice were subjected to three phases of operant training: fixed-ratio 1 (FR1), fixed-ratio 5 (FR5) and progressive ratio (PR) reinforcement schedules. Although no differences were observed in the FR1 and FR5 tasks, HttQ111/+ mice had significantly lower breakpoints in the PR task compared to Htt+/+ mice, suggesting an apathetic phenotype in HttQ111/+ mice. This method is a robust, yet inexpensive alternative to commercial chambers and could be used in future studies to test preclinical therapies. We additionally built a low-cost infrared homecage activity monitoring system: the Circadian Activity and Movement Phenotype Recorder, or CAMPR. This system was used to assess circadian activity in HttQ111/+ mice and can quantify clear distinctions between light and dark phase activity. Together, we have demonstrated that our in-house equipment is a viable alternative to commercial behavioral apparatuses.

Rights

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Language

English

Format

application/pdf

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May 17th, 1:00 PM May 17th, 12:00 PM

Open-Source Alternatives to Investigate Affective and Autonomic Phenotypes in HD Model Mice

Psychology

Huntington's disease (HD) is a neurodegenerative disease classically characterized as a movement disorder, however non-classical symptoms have profound effects on the lives of HD mutation carriers. Apathy is one of the most prevalent psychiatric HD symptoms, is present in early stages, and continues to progress through all stages of the disease. Similarly, circadian dysfunction leads to sleep disturbances in HD patients, exacerbating symptoms and possibly contributing to disease progression. Despite this, current studies in HD mouse models largely focus on motor processes and rarely investigate the effects of these other crucial phenotypes, which may confound behavioral assays intending to measure cognitive, autonomic, and even motor symptoms. Commercial operant conditioning chambers used to assess affective phenotypes have several drawbacks, including high cost, low throughput and limited customizability. We adapted an open-source operant chamber that utilizes off-the-shelf hardware (Rodent Operant Bucket; Devarakonda et al., 2015) to investigate motivational phenotypes in an HD model mouse. HttQ111/+ and wild-type (Htt+/+) mice were subjected to three phases of operant training: fixed-ratio 1 (FR1), fixed-ratio 5 (FR5) and progressive ratio (PR) reinforcement schedules. Although no differences were observed in the FR1 and FR5 tasks, HttQ111/+ mice had significantly lower breakpoints in the PR task compared to Htt+/+ mice, suggesting an apathetic phenotype in HttQ111/+ mice. This method is a robust, yet inexpensive alternative to commercial chambers and could be used in future studies to test preclinical therapies. We additionally built a low-cost infrared homecage activity monitoring system: the Circadian Activity and Movement Phenotype Recorder, or CAMPR. This system was used to assess circadian activity in HttQ111/+ mice and can quantify clear distinctions between light and dark phase activity. Together, we have demonstrated that our in-house equipment is a viable alternative to commercial behavioral apparatuses.