Long-term home cage activity scans reveal lowered exploratory behaviour in symptomatic female Rett mice

•Mecp2Stop mutant female mice develop Rett-like symptoms late in life (>6 months).•Symptoms include anomalies in motor, activity and anxiety profiles and were assessed in various behavioural tasks.•Deficits occurred in ambulatory activity during novelty exploration and habituation to a novel envi...

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Bibliographic Details
Published in:	Behavioural brain research 2013-08, Vol.250, p.148-156
Main Authors:	Robinson, Lianne, Plano, Andrea, Cobb, Stuart, Riedel, Gernot
Format:	Article
Language:	eng
Subjects:	Animals Anxiety - etiology Anxiety - genetics Behavioral psychophysiology Biological and medical sciences Body Weight - genetics Circadian Rhythm - genetics Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Disease Models, Animal Disease Progression Environment Exploratory Behavior - physiology Female Fundamental and applied biological sciences. Psychology Locomotor activity Maze Learning - physiology Mecp2 Medical sciences Methyl-CpG-Binding Protein 2 - genetics Mice Mice, Inbred C57BL Mice, Transgenic Motor Activity - genetics Mutation - genetics Neurology Non-associative learning Phenotype Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Research Report Rett syndrome Rett Syndrome - genetics Rett Syndrome - physiopathology
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Summary:	•Mecp2Stop mutant female mice develop Rett-like symptoms late in life (>6 months).•Symptoms include anomalies in motor, activity and anxiety profiles and were assessed in various behavioural tasks.•Deficits occurred in ambulatory activity during novelty exploration and habituation to a novel environment.•Circadian rhythms and anxiety were not affected, but food intake was higher and global activity lower in mutant mice. 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 Mecp2Stop 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, Mecp2Stop 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 Mecp2Stop mice. These data confirm the slow and progressive development of Rett-like symptoms in female Mecp2Stop 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.
ISSN:	0166-4328 1872-7549