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. 2013 Aug 1;250(100):148-56.
doi: 10.1016/j.bbr.2013.04.041. Epub 2013 May 1.

Long-term Home Cage Activity Scans Reveal Lowered Exploratory Behaviour in Symptomatic Female Rett Mice

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Free PMC article

Long-term Home Cage Activity Scans Reveal Lowered Exploratory Behaviour in Symptomatic Female Rett Mice

Lianne Robinson et al. Behav Brain Res. .
Free PMC article

Abstract

Numerous experimental models have been developed to reiterate endophenotypes of Rett syndrome, a neurodevelopmental disorder with a multitude of motor, cognitive and vegetative symptoms. Here, female Mecp2(Stop) mice [1] were characterised at mild symptomatic conditions in tests for anxiety (open field, elevated plus maze) and home cage observation systems for food intake, locomotor activity and circadian rhythms. Aged 8-9 months, Mecp2(Stop) mice presented with heightened body weight, lower overall activity in the open field, but no anxiety phenotype. Although home cage activity scans conducted in two different observation systems, PhenoMaster and PhenoTyper, confirmed normal circadian activity, they revealed severely compromised habituation to a novel environment in all parameters registered including those derived from a non-linear decay model such as initial exploration maximum, decay half-life of activity and span, as well as plateau. Furthermore, overall activity was significantly reduced in nocturnal periods due to reductions in both fast ambulatory movements, but also a slow lingering. In contrast, light-period activity profiles during which the amount of sleep was highest remained normal in Mecp2(Stop) mice. These data confirm the slow and progressive development of Rett-like symptoms in female Mecp2(Stop) mice resulting in a prominent reduction of overall locomotor activity, while circadian rhythms are maintained. Alterations in the time-course of habituation may indicate deficiencies in cognitive processing.

Figures

Fig. 1
Fig. 1
Symptom severity score, body weight and anxiety-related behaviour of Mecp2Stop mice. Means ± SEM. (A) Mecp2Stop mice presented with a progressively increasing symptom score, which attained a mean of 5/6 in weeks 16–24 of testing. (B) Mecp2Stop mice also displayed a sustained increase in body weight compared to WT's. Shaded area indicates period of behavioural assessment. (C) Ambulatory activity in the open field during 10 min of recording plotted in minute bins. Mecp2Stop mice presented with reduced locomotor activity. No reliable habituation occurred in either WT or Mecp2Stop mice. Fear-signalling visits to the centre of the open field (D) or open arms of the elevated plus maze (E) was not affected by transgene knockout. *p < 0.05.
Fig. 2
Fig. 2
Habituation of Mecp2Stop and WT mice to novel home cages recorded by the PhenoMaster. Animals were recorded upon introduction to the novel cage in 10-min bins for 3 h (habituation complete in WT mice). Mean ± SEM. (A) Activity profiling confirmed higher activity in WT during early phases of habituation (asterisks are for 10–30 min, p < 0.01). (B) High resolution plot of first 10 min in novel cage. Again, Mecp2Stop mice show lower ambulations relative to WT (compare with Fig. 1C). (C) One-phase exponential decay fitted to model typical WT habituation profile following equation y = (Y0 − plateau)ekt + plateau (for details, see Section 2). Data represent means ± SEM and dotted lines indicate theoretically calculated 95% confidence intervals. As is obvious, Mecp2Stop mice followed a different habituation profile. Consequently maximal locomotor activity (Y0), the asymptotic plateau, the decay half life, and span (range between max and min activity) are significantly different between genotypes (D). Note that left bar for each parameter represents data for WT cohort; data are mean with 95% confidence interval. Asterisks: p < 0.05. Overall, WT mice showed faster habituation. *p < 0.05; **p < 0.01.
Fig. 3
Fig. 3
Home cage activity as recorded by PhenoMaster. Means ± SEM. (A) Circadian activity over a 24-h period (shaded area indicates dark hours, 19:00–07:00). Mecp2Stop mice were less active during the dark phase with a strong locomotor deficit apparent at 2–6 h of the dark phase. Indeed, nocturnal activity was significantly higher in WT mice (Bi), but not during light phases (Bii), and was due to reductions in both ambulatory (Ci) and fine movements (Cii). Automatically monitored food intake was higher in Mecp2Stop mice on all recording days (Di) and increased cumulative food intake over 3 days was due to nocturnal eating (Dii). *p < 0.05; ***p < 0.001.
Fig. 4
Fig. 4
Home cage activity as recorded by PhenoTyper. Means ± SEM. (A) Circadian activity over a 24-h period (shaded area indicates dark hours, 19:00–07:00). Mecp2Stop mice were less active relative to WT during the dark hours with a strong locomotor deficit apparent at 2–5 h of the dark phase. Nocturnal activity was significantly higher in WT mice (Bi), but not diurnal locomotion (Bii). Locomotion of WT mice was concentrated towards the edges of their home cage (patrolling zone: grey shaded area) in which they performed more patrolling (Ci), while Mecp2Stop mice spent less time in this zone. This was not related to lower ambulatory activity since both WT and Mecp2Stop mice entered the zone with the same frequency (Cii). A reliable difference was also evident for time spent in food zone (shaded area: in front of food hopper) (D) in keeping with food intake data from the PhenoMaster (Fig. 3D). *p < 0.05.

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References

    1. Guy J., Gan J., Selfridge J., Cobb S., Bird A. Reversal of neurological defects in a mouse model of Rett syndrome. Science. 2007;315:1143–1147. - PubMed
    1. Hagberg B., Aicardi J., Dias K., Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome. Report of 35 cases. Annals of Neurology. 1983;14:471–479. - PubMed
    1. Amir R.E., Van den Veyver I.B., Wan M., Tran C.Q., Francke U., Zoghbi H.Y. Rett syndrome is caused by mutations in X linked MECP2, encoding methyl-Cp G binding protein 2. Nature Genetics. 1999;23:185–188. - PubMed
    1. Chen R.Z., Akbarian S., Tudor M., Jaenisch R. Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nature Genetics. 2001;27:327–331. - PubMed
    1. Guy J., Hendrich B., Holmes M., Martin J.E., Bird A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nature Genetics. 2001;27:322–326. - PubMed

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