Intranasal oxytocin administration rescues neonatal thermo-sensory deficit in mouse model of Autism

Abstract

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage is unknown. Here we investigated cool thermosensibility during the first week of mouse life. In response to cool temperature exposure control neonates undertake innate behaviors by eliciting low-latency ultrasonic vocalization. However, we found that neonatal mice lacking the autism-associated gene Magel2 fail to react to cool stimuli while long-term thermoregulatory function, namely nonshivering thermogenesis, is active. Investigation of the sensory pathway revealed abnormal cool-induced response in the medial preoptic area.Importantly, intranasal administration of oxytocin can rescue this thermosensory reactivity. In addition, chemogenetic inactivation in control neonates of hypothalamic oxytocin neurons reproduces the coolness response failure observed in Magel2 mutants. Collectively, these findings establish for the first-time impairments of thermal lower-reactivity in a mouse model of ASD with deletion of Magel2 gene during early life period and reveal that the oxytocinergic system regulates this neonatal cool thermosensibility.