INVESTIGATING THE NEURAL MECHANISMS UNDERLYING THE ASSIGNMENT OF EMOTIONAL VALUE TO SOCIAL STIMULI IN A MOUSE MODEL OF ASD

Autism Spectrum Disorder (ASD) is characterized by profound social communication deficits, often related to an impaired ability to attribute emotional significance to socially relevant sensory cues. Clarifying the neural basis of these associative emotional processes could help in understanding the social abnormalities that define the disorder.
Since olfaction is the primary cue used by rodents for social interaction, we focused on the posterior piriform cortex (PPC), a higher-order cortex involved in olfactory processing and integration of sensory stimuli with emotional value.
We investigated whether the neuronal population responsible for assigning incentive value to sensory stimuli also contributes to social behavior in wild-type (WT) mice. Using a viral-based activity-dependent tagging approach, we assess the cellular overlap between neuronal ensembles engaged in appetitive conditioning and those recruited during social interaction. Furthermore, chemogenetic silencing determined whether neurons involved in appetitive events are functionally necessary for social behavior.
We extended this paradigm to the Shank3b KO mouse model of autism, quantifying the appetitive-social neuronal overlap in the PPC to evaluate whether differences compared to WT littermates could explain the impaired social behavior typical of this ASD model.
Lastly, we investigated the role of dopamine in associating sensory stimuli to emotional value by examining the expression of both D1 and D2 receptors in the PPC neurons and assessing potential differences between WT and SHANK3b KO mice.
Our findings aim to clarify whether social impairment in ASD is driven by a deficit in assigning emotional value to social experiences and how this phenotype might be rescued.