Neurobehavioural disorders in the infant reeler mouse model: interaction of genetic vulnerability and consequences of maternal separation.

Studies on heterozygous (HZ) reeler mice suggest a relationship between reelin (a protein of extra cellular matrix) haploinsufficiency and the presence of altered neural networks and behaviour. Neonatal adverse and/or stimulating experiences might interfere with the emergence of this genetic-dependent phenotype. Repeated episodes of maternal separation early in ontogeny result in enduring neuroendocrine, neurochemical and behavioural alterations in the offspring. Therefore, in order to investigate whether developmental indexes of neurobehavioural disorders can be studied in the infant reeler mouse model, and whether ontogenetic adverse experiences may question or improve its suitability, homozygous reeler (RL), heterozygous (HZ) and wild-type (WT) mouse pups underwent maternal separation (SEP, 5h/day) or handling (H, 3min/day) on PND 2-6. As expected, a sex difference appeared, for measure of emotional and communicative behaviour in infant mice. On PND 7, compared to other genotypes, RL mouse pups from the H control group, showed reduced levels of ultrasound (USV) production and of locomotion. Surprisingly, this deficit in RL mice was fully reverted by maternal separation. Maternal separation per se reduced social motivation in the homing test at PND 9 in WT mice, with no effects on HZ and RL ones. Additionally, female pups emitted much lower levels of ultrasound production than males within the H control group. Such a baseline sex difference, however, disappeared in the SEP group. The present results provide evidence that unusual stress and related hormonal stimulation early in development may (i) independently shape individual phenotype and (ii) interact with a genetic make-up to substantially modify its "natural" developmental trajectories.