Acquisition and reversal of visual discrimination learning in APPSwDI/Nos2−/− (CVN) mice

Piiponniemi, Tuukka O.; Bragge, Timo; Vauhkonen, Eveliina E.; Vartiainen, Petra; Puoliväli, Jukka; Sweeney, Patrick J.; Kopanitsa, Maksym V.

doi:10.1016/j.neulet.2017.04.049

Cited by 16 publications

(15 citation statements)

References 32 publications

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“…One-sample t -test was used to assess the difference of the group mean from a theoretical value. In our previous study (Piiponniemi et al, 2017 ) we noticed that within-session reaction times and reward collection latencies were right-skewed even after log10 or square root transformations. Therefore, for between-genotype comparisons, session median rather than session mean values of these parameters from individual mice were used, because they were more robust to the effect of outliers and more representative as central tendency measures for each session.…”

Section: Methodsmentioning

confidence: 80%

Impaired Performance of the Q175 Mouse Model of Huntington’s Disease in the Touch Screen Paired Associates Learning Task

Piiponniemi¹,

Parkkari²,

Heikkinen³

et al. 2018

Front. Behav. Neurosci.

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Cognitive disturbances often predate characteristic motor dysfunction in individuals with Huntington’s disease (HD) and place an increasing burden on the HD patients and caregivers with the progression of the disorder. Therefore, application of maximally translational cognitive tests to animal models of HD is imperative for the development of treatments that could alleviate cognitive decline in human patients. Here, we examined the performance of the Q175 mouse knock-in model of HD in the touch screen version of the paired associates learning (PAL) task. We found that 10–11-month-old heterozygous Q175 mice had severely attenuated learning curve in the PAL task, which was conceptually similar to previously documented impaired performance of individuals with HD in the PAL task of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Besides high rate of errors in PAL task, Q175 mice exhibited considerably lower responding rate than age-matched wild-type (WT) animals. Our examination of effortful operant responding during fixed ratio (FR) and progressive ratio (PR) reinforcement schedules in a separate cohort of similar age confirmed slower and unselective performance of mutant animals, as observed during PAL task, but suggested that motivation to work for nutritional reward in the touch screen setting was similar in Q175 and WT mice. We also demonstrated that pronounced sensorimotor disturbances in Q175 mice can be detected at early touch screen testing stages, (e.g., during “Punish Incorrect” phase of operant pretraining), so we propose that shorter test routines may be utilised for more expedient studies of treatments aimed at the rescue of HD-related phenotype.

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Section: Methodsmentioning

confidence: 80%

Impaired Performance of the Q175 Mouse Model of Huntington’s Disease in the Touch Screen Paired Associates Learning Task

Piiponniemi¹,

Parkkari²,

Heikkinen³

et al. 2018

Front. Behav. Neurosci.

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“…However, a previous study reported significantly improved performance in TgCRND8 (4.5-months of age) mice during the reversal phase [24]. By contrast, APPSwDl/Nos2 −/− (4-5 months of age) and APPS1-21 (6 months of age) mice exhibited impaired performance in the reversal learning task [53,54]. Medial prefrontal cortex lesions facilitate reversal learning in mice [55], whereas lesions of the orbitofrontal cortex impair reversal learning [56,57].…”

Section: Discussionmentioning

confidence: 88%

Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer’s disease

et al. 2020

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline with accumulation of amyloid beta (Aβ) and neurofibrillary tangles that usually begins 15–30 years before clinical diagnosis. Rodent models that recapitulate aggressive Aβ and/or the pathology of neurofibrillary tangles are essential for AD research. Accordingly, non-invasive early detection systems in these animal models are required to evaluate the phenotypic changes, elucidate the mechanism of disease progression, and facilitate development of novel therapeutic approaches. Although many behavioral tests efficiently reveal cognitive impairments at the later stage of the disease in AD models, it has been challenging to detect such impairments at the early stage. To address this issue, we subjected 4–6-month-old male AppNL−G−F/NL−G−F knock-in (App-KI) mice to touchscreen-based location discrimination (LD), different object–location paired-associate learning (dPAL), and reversal learning tests, and compared the results with those of the classical Morris water maze test. These tests are mainly dependent on the brain regions prone to Aβ accumulation at the earliest stages of the disease. At 4–6 months, considered to represent the early stage of disease when mice exhibit initial deposition of Aβ and slight gliosis, the classical Morris water maze test revealed no difference between groups, whereas touchscreen-based LD and dPAL tasks revealed significant impairments in task performance. Our report is the first to confirm that a systematic touchscreen-based behavioral test battery can sensitively detect the early stage of cognitive decline in an AD-linked App-KI mouse model. This system could be applied in future translational research.

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“…Data was acquired with Abet II software. Dependent variables were total number of sessions, % correct (correction trials not included), and perseveration index PI, with PI = correction trials / incorrect trials (Brigman et al, 2008;Piiponniemi et al, 2017).…”

Section: Visual Discrimination and Reversal Learningmentioning

confidence: 99%

Differential effects of post-training scopolamine on spatial and non-spatial learning tasks in mice

Thonnard

Callaerts-Végh

D’Hooge

2019

Brain Research Bulletin

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Muscarinic antagonist scopolamine has been extensively used to model amnesia in lab rodents, but most studies have focused on the effects of pre-training scopolamine administration. Here, we examined post-training scopolamine administration in C57BL/6JRj mice. Learning was assessed in three different procedures: odor discrimination in a digging paradigm, visual discrimination in a touchscreen-based setup, and spatial learning in the Morris water maze. Scopolamine administration affected performance in the odor discrimination task. More specifically, scopolamine decreased perseverance, which facilitated reversal learning. Similar results were obtained in the visual discrimination task, but scopolamine did not affect performance in the spatial learning task. It is unlikely that these results can be explained by non-memory-related cognitive effects (e.g., attention), non-cognitive behaviours (e.g., locomotor activity) or peripheral side-effects (e.g., mydriasis). They likely relate to the various neuropharmacological actions of scopolamine.

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Acquisition and reversal of visual discrimination learning in APPSwDI/Nos2−/− (CVN) mice

Cited by 16 publications

References 32 publications

Impaired Performance of the Q175 Mouse Model of Huntington’s Disease in the Touch Screen Paired Associates Learning Task

Impaired Performance of the Q175 Mouse Model of Huntington’s Disease in the Touch Screen Paired Associates Learning Task

Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer’s disease

Differential effects of post-training scopolamine on spatial and non-spatial learning tasks in mice

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