Thesis defense Chao Guo (Donders series 476)

24 March 2021

Promotors: prof. dr. J. Homberg,prof. dr. B. Roozendaal

Information Categorization and Generalization: a study on the role of serotonin transporter knockout in rats

Why does a patient with one mental disorder tend to have other mental disorders as well? When investigating the pathogenesis of mental disorders, we have the mindset to classify mental disorders according to symptoms. Perhaps we should change this mindset to understand the pathogenesis of mental illness: what is the common biological basis for comorbid mental disorders? Previous studies found that a rat model lacking the serotonin transporter (5-HTT) showed anxiety-like, depression-like, drug addiction-like, and autism-like behaviors. There may be a common dimension observed at behavior level across these disorders. Such a common dimension might be generalization. Appropriate generalization is fundamental for organisms to adapt to the changes in the environment. It requires the brain to mobilize multiple resources (genes, neurotransmitters, neural circuits, etc.) to encode perceptual information from the environments, decode stored information, and finally generate behavior as output. By establishing a touchscreen based task presenting visual stimuli, generalization can be measured in rats. Using state-of-art computational models, behaviors can be described or predicted by mathematical formulas. This thesis aims to detect generalization in rats by designing novel behavioral paradigms and using computational models to understand the effect of 5-HTT knockout on generalization.