title: Predictable enriched environment prevents development of hyper-emotionality in the VPA rat model of autism.
abstract: Understanding the effects of environmental stimulation in autism can improve therapeutic interventions against debilitating sensory overload, social withdrawal, fear and anxiety. Here, we evaluate the role of environmental predictability on behavior and protein expression, and inter-individual differences, in the valproic acid (VPA) model of autism. Male rats embryonically exposed (E11.5) either to VPA, a known autism risk factor in humans, or to saline, were housed from weaning into adulthood in a standard laboratory environment, an unpredictably enriched environment, or a predictably enriched environment. Animals were tested for sociability, nociception, stereotypy, fear conditioning and anxiety, and for tissue content of glutamate signaling proteins in the primary somatosensory cortex, hippocampus and amygdala, and of corticosterone in plasma, amygdala and hippocampus. Standard group analyses on separate measures were complemented with a composite emotionality score, using Cronbach's Alpha analysis, and with multivariate profiling of individual animals, using Hierarchical Cluster Analysis. We found that predictable environmental enrichment prevented the development of hyper-emotionality in the VPA-exposed group, while unpredictable enrichment did not. Individual variation in the severity of the autistic-like symptoms (fear, anxiety, social withdrawal and sensory abnormalities) correlated with neurochemical profiles, and predicted their responsiveness to predictability in the environment. In controls, the association between socio-affective behaviors, neurochemical profiles and environmental predictability was negligible. This study suggests that rearing in a predictable environment prevents the development of hyper-emotional features in animals exposed to an autism risk factor, and demonstrates that unpredictable environments can lead to negative outcomes, even in the presence of environmental enrichment.
authors.affiliation: Laboratory of Neural Microcircuits, Brain Mind Institute, École Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Mônica R
authors.initials: MR
authors.lastname: Favre
authors.affiliation: Laboratory of Neural Microcircuits, Brain Mind Institute, École Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Deborah
authors.initials: D
authors.lastname: La Mendola
authors.affiliation: Laboratory of Neural Microcircuits, Brain Mind Institute, École Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Julie
authors.initials: J
authors.lastname: Meystre
authors.affiliation: Laboratory of Neural Microcircuits, Brain Mind Institute, École Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Christodoulou
authors.affiliation: Laboratory of Neural Microcircuits, Brain Mind Institute, École Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Cochrane
authors.affiliation: Laboratory of Neural Microcircuits, Brain Mind Institute, École Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Henry
authors.initials: H
authors.lastname: Markram
authors.affiliation: Laboratory of Neural Microcircuits, Brain Mind Institute, École Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Markram
keywords: autism; emotion; environmental enrichment; individual differences; predictability; protein expression; rat; valproic acid