The neural basis of sensory-driven emotional learning and its impact on social deficits in autism spectrum model

The ability to assign emotional value to sensory cues, such as odours and sounds, through associations with rewards or punishments, is fundamental for adaptive behaviour. This process is often impaired in individuals with autism spectrum disorder (ASD), who exhibit altered sensory processing and difficulties in recognizing emotions, as well as social deficits. In this project, we investigated the neural mechanisms underlying the encoding of emotional events associated with sensory stimuli and their involvement in social interactions in both wild-type (WT) and ASD mouse models (Shank3b-/-), where these processes remain poorly understood. We specifically focused on olfactory sensory stimuli, which play crucial roles in shaping animal social behaviour and gain incentive emotional significance during positive experiences, such as appetitive rewards and social interactions. Behavioural analyses revealed that, while Shank3b-/- (KO) mice are able to form an association between an odour and a food reward, they displayed impairments in maintaining this learned association over time. In addition, social behaviour assessments confirmed significant deficits in social interactions in KO mice, coherently with the notion that social motivation is altered in ASD models. At the cellular level, we employed an inducible viral tagging approach to study the overlap between neuronal population activated during appetitive learning and those engaged in social interactions. Our preliminary results suggest that WT mice exhibited a significant overlap between these neural circuits, suggesting that social stimuli may recruit reward-related pathways. In contrast, this overlapping neuronal circuits were significantly reduced in KO mice: this suggests that social experiences may not be rewarding for ASD mice as they are for WT, potentially contributing to their diminished social motivation. This paves the way for a deeper understanding of the underlying causes of autism-related alterations and the development of novel therapeutic strategies to mitigate its symptoms.