Open-Source Alternatives to Investigate Affective and Autonomic Phenotypes in HD Model Mice
Research Mentor(s)
Carroll, Jeffrey B. (Jeffrey Bryan), 1977-
Description
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.
Document Type
Event
Start Date
17-5-2017 1:00 PM
End Date
17-5-2017 12:00 PM
Department
Psychology
Genre/Form
student projects; posters
Subjects – Topical (LCSH)
Huntington's disease--Animal models; Huntington's disease--Research
Type
Image
Rights
Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this documentation for commercial purposes, or for financial gain, shall not be allowed without the author's written permission.
Language
English
Format
application/pdf
Open-Source Alternatives to Investigate Affective and Autonomic Phenotypes in HD Model Mice
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.