PhD defence Alexandra Abromeit
From synapse to sensory signatures in autism
Sensory phenotypes and underlying molecular mechanisms in genetic mouse models
Autistic people often experience the sensory world differently. Everyday sounds may feel overwhelming, a light touch may be uncomfortable, or sensory information may be difficult to filter. These differences can strongly affect daily life, yet we still know relatively little about the biology behind them. In this thesis, I investigated how genetic changes linked to autism affect sensory processing and how these effects develop over time. I first combined results from almost 200 published animal studies to identify biological changes that repeatedly occur across different models of autism. This revealed recurring changes in cellular processes involved in regulating and recycling proteins. I then studied three mouse models carrying alterations in different autism-associated genes. All three showed differences in sensory processing, but not in the same way or at the same age. Their underlying molecular changes also differed. This suggests that different genetic changes can lead to sensory differences through different biological routes. Importantly, changing a biological pathway that is altered in an autism model did not necessarily improve sensory behavior. Even when a treatment successfully affected its intended molecular target, sensory differences remained. Therefore, a biological change associated with autism therefore does not automatically represent an effective treatment target. Together, this research shows that sensory differences are a common but dynamic feature across genetic models of autism, while the biology behind them varies. Understanding what these models share and where they differ can help connect genetic variation to sensory processing and guide more targeted future research.