Early Detection of Apathetic Phenotypes in Huntington's Disease Knock-in Mice Using Open Source Tools.

Autor: Minnig S; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Bragg RM; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Tiwana HS; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Solem WT; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Hovander WS; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Vik ES; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Hamilton M; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Legg SRW; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Shuttleworth DD; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Coffey SR; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Cantle JP; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States., Carroll JB; Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, 98225, United States. jeff.carroll@wwu.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Feb 02; Vol. 8 (1), pp. 2304. Date of Electronic Publication: 2018 Feb 02.
DOI: 10.1038/s41598-018-20607-7
Abstrakt: Apathy is one of the most prevalent and progressive psychiatric symptoms in Huntington's disease (HD) patients. However, preclinical work in HD mouse models tends to focus on molecular and motor, rather than affective, phenotypes. Measuring behavior in mice often produces noisy data and requires large cohorts to detect phenotypic rescue with appropriate power. The operant equipment necessary for measuring affective phenotypes is typically expensive, proprietary to commercial entities, and bulky which can render adequately sized mouse cohorts as cost-prohibitive. Thus, we describe here a home-built, open-source alternative to commercial hardware that is reliable, scalable, and reproducible. Using off-the-shelf hardware, we adapted and built several of the rodent operant buckets (ROBucket) to test Htt Q111/+ mice for attention deficits in fixed ratio (FR) and progressive ratio (PR) tasks. We find that, despite normal performance in reward attainment in the FR task, Htt Q111/+ mice exhibit reduced PR performance at 9-11 months of age, suggesting motivational deficits. We replicated this in two independent cohorts, demonstrating the reliability and utility of both the apathetic phenotype, and these ROBuckets, for preclinical HD studies.
Databáze: MEDLINE