Social dysfunction is among the most prominent features of autism spectrum disorder (ASD). Despite a growing understanding of its genetic and micro-anatomic underpinnings, little is known about how ASD influences the cellular encoding of social information or how disruption of neuronal encoding relates to abnormal social behavior. Here, we show that neurons in the mouse medial prefrontal cortex (mPFC) encode social information referentially; meaning that they represent another's positive and negative experiences differentially but that they also distinguish another's experience from the animal's own. Loss of Shank3 expression, a major gene associated with ASD, leads to a diminished ability by neurons to encode another's experience but also produces a proportional increase in neuronal response to the animal's own. This selective lack of response to another's experience (i.e., 'what' they are experiencing) is associated with an inability to distinguish between other-and-self but does not adversely affect their ability to encode the other's identity (i.e., 'who' is experiencing it). Our study suggests a neuronal encoding substrate for ASD that may represent a putative target to functionally restore social encoding within mature adult cells.
