Abstract
Disorganization is a core feature of schizophrenia that manifests across multiple domains, including communication and motor function, yet there is much work to be done to understand this dysfunction in order to enable better treatment. This thesis investigated how early neurodevelopmental immune challenge affects behavioural sequencing and coordination, using a maternal immune activation (MIA) model of schizophrenia risk in rats. Through novel applications of machine learning, including automated classification of ultrasonic vocalisations (USVs) and pose estimation of movement, we examined parallel disruptions across vocal and motor domains. After developing and validating a supervised USV classification system enhanced by synthetic training data, we analyzed vocal sequences across social and reward contexts. While MIA offspring maintained normal call production abilities, they showed increased variability in bout structure across two independent datasets, and altered transitional probabilities between calls during reward-related behaviours. A playback study investigating USV processing revealed limited evidence for altered preference between common and uncommon call types in MIA offspring, though competing behavioural drives in the task design made interpretation challenging. An investigation of motor coordination revealed sex-dependent effects. Male MIA rats exhibited increased variability in stride length and higher rates of foot faults while maintaining normal locomotion speed, whereas female motor function was relatively preserved. This dynamic of preserved basic abilities, alongside disrupted sequential organization, suggests MIA may specifically affect mechanisms involved in behavioural organization and coordination rather than lower-level production capabilities. These findings parallel aspects of disorganization observed in schizophrenia and suggest early immune-related brain insult may impact core mechanisms underlying behavioural organization. Additionally, we demonstrated that individually ventilated cages severely attenuate USV transmission between cages, which has implications for both research methodology and animal welfare. Together, these results validate and extend the MIA model while providing some novel analytical approaches for investigating behavioural organization in MIA rodent studies. The observed parallels between disrupted organisation in both vocal and motor domains offer new behavioural assays for investigating organisational deficits in II MIA rats, potentially enabling development of novel treatments for aspects of schizophrenia where current therapeutic options are limited.