Automated phenotyping and advanced data mining exemplified in rats transgenic for Huntington's disease

Urbach, Yvonne K.; Raber, Kerstin; Canneva, Fabio; Plank, Anne-Christine; Andreasson, Theresa; Ponten, Henrik; Kullingsjö, Johan; Nguyen, Huu Phuc; Rieß, Olaf; Hörsten, Stephan von

doi:10.1016/j.jneumeth.2014.06.017

Cited by 42 publications

(52 citation statements)

References 35 publications

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“…This phenotype has been found in almost all operant conditioning tests that have been run with the BACHD rats at our institute (seven longitudinal studies) and is described in previous publications [31]. Interestingly, similar phenotypes have been found in transgenic rats that carry a fragment of the HD-causing gene (TgHD rats) [34]. In the current study, the non-matching to position protocol offered additional information regarding this phenotype.…”

Section: Discussionsupporting

confidence: 77%

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory

Clemensson

Rieß

et al. 2017

PLoS ONE

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The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

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Section: Discussionsupporting

confidence: 77%

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory

Clemensson

Rieß

et al. 2017

PLoS ONE

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“…However, for the assessment of rat cognitive abilities using mazes or automated-operant systems (e.g., the Morris water maze or Skinner boxes), repetitive animal handling between sessions, which brings variations in rat stress levels, could significantly affect their cognitive performance [9]. One approach to eliminating animal handling is relocating the operant testing modules to inside the home cages [10,11] of group living mice or rats. The screening of cognitive and affective abilities of group living rodents is therefore made possible in an environment in which they are undisturbed and where they follow their own cycle of activity and level of motivation for extended periods of time.…”

Section: Introductionmentioning

confidence: 99%

An Automated, Experimenter-Free Method for the Standardised, Operant Cognitive Testing of Rats

et al. 2017

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Animal models of human pathology are essential for biomedical research. However, a recurring issue in the use of animal models is the poor reproducibility of behavioural and physiological findings within and between laboratories. The most critical factor influencing this issue remains the experimenter themselves. One solution is the use of procedures devoid of human intervention. We present a novel approach to experimenter-free testing cognitive abilities in rats, by combining undisturbed group housing with automated, standardized and individual operant testing. This experimenter-free system consisted of an automated-operant system (Bussey-Saksida rat touch screen) connected to a home cage containing group living rats via an automated animal sorter (PhenoSys). The automated animal sorter, which is based on radio-frequency identification (RFID) technology, functioned as a mechanical replacement of the experimenter. Rats learnt to regularly and individually enter the operant chamber and remained there for the duration of the experimental session only. Self-motivated rats acquired the complex touch screen task of trial-unique non-matching to location (TUNL) in half the time reported for animals that were manually placed into the operant chamber. Rat performance was similar between the two groups within our laboratory, and comparable to previously published results obtained elsewhere. This reproducibility, both within and between laboratories, confirms the validity of this approach. In addition, automation reduced daily experimental time by 80%, eliminated animal handling, and reduced equipment cost. This automated, experimenter-free setup is a promising tool of great potential for testing a large variety of functions with full automation in future studies.

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“…It is worth noting that our results were obtained using female tgHD rats, in which a less severe course of the disease has been reported compared to male tgHD rats at the behavioral, physiological and neuropathological levels (Bode et al, 2008; Urbach et al, 2014). One could wonder now when impulsivity emerges in the course of the disease in tgHD male and female animals.…”

Section: Resultsmentioning

confidence: 72%

Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

Massioui

Lamirault

Yagüe

et al. 2016

Front. Behav. Neurosci.

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Cognitive deficits associated with Huntington disease (HD) are generally dominated by executive function disorders often associated with disinhibition and impulsivity/compulsivity. Few studies have directly examined symptoms and consequences of behavioral disinhibition in HD and its relation with decision-making. To assess the different forms of impulsivity in a transgenic model of HD (tgHD rats), two tasks assessing cognitive/choice impulsivity were used: risky decision-making with a rat gambling task (RGT) and intertemporal choices with a delay discounting task (DD). To assess waiting or action impulsivity the differential reinforcement of low rate of responding task (DRL) was used. In parallel, the volume as well as cellular activity of the amygdala was analyzed. In contrast to WT rats, 15 months old tgHD rats exhibited a poor efficiency in the RGT task with difficulties to choose advantageous options, a steep DD curve as delays increased in the DD task and a high rate of premature and bursts responses in the DRL task. tgHD rats also demonstrated a concomitant and correlated presence of both action and cognitive/choice impulsivity in contrast to wild type (WT) animals. Moreover, a reduced volume associated with an increased basal cellular activity of the central nucleus of amygdala indicated a dysfunctional amygdala in tgHD rats, which could underlie inhibitory dyscontrol. In conclusion, tgHD rats are a good model for impulsivity disorder that could be used more widely to identify potential pharmacotherapies to treat these invasive symptoms in HD.

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Automated phenotyping and advanced data mining exemplified in rats transgenic for Huntington's disease

Cited by 42 publications

References 35 publications

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory

An Automated, Experimenter-Free Method for the Standardised, Operant Cognitive Testing of Rats

Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

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