Assessing Cognition in Mice

Hölter, Sabine M.; Garrett, Lillian; Einicke, Jan; Sperling, Bettina; Dirscherl, Petra; Zimprich, Annemarie; Fuchs, Helmut; Gailus‐Durner, Valérie; Angelis, Martin Hrabé de; Wurst, Wolfgang

doi:10.1002/9780470942390.mo150068

Cited by 78 publications

(58 citation statements)

References 67 publications

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“…Y-maze. Spontaneous alternation in the Y-maze was tested during the first half of the light phase and as described previously 48 . The apparatus was made of opaque light grey polyvinyl chloride and had three identical arms (30 × 5 × 15 cm 3 ) placed at 120° from each other; illumination in the centre of the maze was 100 lx.…”

Section: Methodsmentioning

confidence: 99%

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Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

et al. 2018

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Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in ~1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.

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Section: Methodsmentioning

confidence: 99%

“…Object recognition. The object-recognition test was carried out during the light phase and as described previously 48 . In brief, each mouse was allowed to explore two identical objects three times for 5 min, with an inter-trial interval of 15 min.…”

Section: Methodsmentioning

confidence: 99%

Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

et al. 2018

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“…c Timeline of the conducted comprehensive behavioral test battery to assess memory, sensorimotor gating, locomotor activity, and anxiety-related behavior. For all three mutant mouse lines, we performed open field, prepulse inhibition (PPI), acoustic startle response (ASR), social discrimination (SD), and Ymaze chronologically in the specified sequence with the age in weeks shown below by Hölter et al [29]. After a 2 h habituation period in a fresh 186 cage, test animals were exposed to stimulus animals (ovariec-187 tomized 129Sv females).…”

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confidence: 99%

Crybb2 Mutations Consistently Affect Schizophrenia Endophenotypes in Mice

et al. 2018

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As part of the βγ-superfamily, βB2-crystallin (CRYBB2) is an ocular structural protein in the lens, and mutation of the corresponding gene can cause cataracts. CRYBB2 also is expressed in non-lens tissue such as the adult mouse brain and is associated with neuropsychiatric disorders such as schizophrenia. Nevertheless, the robustness of this association as well as how CRYBB2 may contribute to disease-relevant phenotypes is unknown. To add further clarity to this issue, we performed a comprehensive analysis of behavioral and neurohistological alterations in mice with an allelic series of mutations in the C-terminal end of the Crybb2 gene. Behavioral Q2 phenotyping of these three βB2-mutant lines Crybb2 O377 , Crybb2 Philly , and Crybb2 Aey2 included assessment of exploratory activity and anxiety-related behavior in the open field, sensorimotor gating measured by prepulse inhibition (PPI) of the acoustic startle reflex, cognitive performance measured by social discrimination, and spontaneous alternation in the Y-maze. In each mutant line, we also quantified the number of parvalbumin-positive (PV+) GABAergic interneurons in selected brain regions that express CRYBB2. While there were allele-specific differences in individual behaviors and affected brain areas, all three mutant lines exhibited consistent alterations in PPI that paralleled alterations in the PV+ cell number in the thalamic reticular nucleus (TRN). The direction of the PPI change mirrored that of the TRN PV+ cell number thereby suggesting a role for TRN PV+ cell number in modulating PPI. Moreover, as both altered PPI and PV+ cell number are schizophrenia-associated endophenotypes, our result implicates mutated Crybb2 in the development of this neuropsychiatric disorder. Keywords Crybb2. Schizophrenia. Parvalbumin. Prepulse inhibition (PPI). Thalamic reticular nucleus (TRN) mouse brain function [1-3]. Although molecular mechanisms 33 of Crybb2 lens fiber and epithelial cell activity are established, 34 work continues on mouse brain pleiotropic effects [4, 5]. As 35 βγ-crystallins constitute a separate class of Ca 2+-binding Electronic supplementary material The online version of this article (

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“…Spontaneous alternations, alternate arm returns and entries were assessed using the Y-Maze as reported previously 19,20 . The Y maze was composed of opaque light grey PVC and had three identical arms (30 × 5 × 15 cm) placed at 120°from each other.…”

Section: Y Mazementioning

confidence: 99%

A truncating Aspm allele leads to a complex cognitive phenotype and region-specific reductions in parvalbuminergic neurons

et al. 2020

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Neurodevelopmental disorders are heterogeneous and identifying shared genetic aetiologies and converging signalling pathways affected could improve disease diagnosis and treatment. Truncating mutations of the abnormal spindle-like microcephaly associated (ASPM) gene cause autosomal recessive primary microcephaly (MCPH) in humans. ASPM is a positive regulator of Wnt/β-Catenin signalling and controls symmetric to asymmetric cell division. This process balances neural progenitor proliferation with differentiation during embryogenesis, the malfunction of which could interfere with normal brain development. ASPM mutations may play a role also in other neurodevelopmental disorders, nevertheless, we lack the details of how or to what extent. We therefore assessed neurodevelopmental disease and circuit endophenotypes in mice with a truncating Aspm 1-7 mutation. Aspm 1-7 mice exhibited impaired short-and long-term object recognition memory and markedly enhanced place learning in the IntelliCage®. This behaviour pattern is reminiscent of a cognitive phenotype seen in mouse models and patients with a rare form of autism spectrum disorder (ASD) as well as in mouse models of altered Wnt signalling. These alterations were accompanied by ventriculomegaly, corpus callosum dysgenesis and decreased parvalbumin (PV)+ interneuron numbers in the hippocampal Cornu Ammonis (CA) region and thalamic reticular nucleus (TRN). PV+ cell number correlated to object recognition (CA and TRN) and place learning (TRN). This opens the possibility that, as well as causing MCPH, mutant ASPM potentially contributes to other neurodevelopmental disorders such as ASD through altered parvalbuminergic interneuron development affecting cognitive behaviour. These findings provide important information for understanding the genetic overlap and improved treatment of neurodevelopmental disorders associated with ASPM.

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Assessing Cognition in Mice

Cited by 78 publications

References 67 publications

Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

Crybb2 Mutations Consistently Affect Schizophrenia Endophenotypes in Mice

A truncating Aspm allele leads to a complex cognitive phenotype and region-specific reductions in parvalbuminergic neurons

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