PhD defence L.F. (Lucas) Wahl

Below is a brief summary of the dissertation: 

In this thesis, we describe several advancements in the analysis of behavioral phenotyping of autism mouse models. We develop novel methods to both standardize and automate the analysis of stereotyped behaviors in chapter 2 and motor function in chapter 3, to expand our understanding of the meaning behind some of the behavioral tests that were used. We also use these tools to increase our understanding of the behavioral spectrum of autism, originating from either primary immunodeficiency disorders in chapter 4 or genetic mutations in autism risk genes and disorders commonly associated with autism in chapter 5. We combine the recent advances in automated classification of both discrete behaviors and underlying behavioral syllables in chapter 5 to develop a new dimensionality reduction method that can be applied to a range of behavioral data, to show meaningful lower-dimensional behavioral dynamics capturing sex- and environment-dependent variability of behavioral phenotypes in autism mouse models. We aim to quantify some of the behavioral variability shown in mouse models of autism, to encourage standardization in the field of behavioral phenotyping of autism mouse models. We further build on this in chapter 6, where we summarize the behavioral and physiological phenotypes which have been described in cerebellar-specific genetic and circuit perturbations of autism risk factors, to gain insight into the range of observable characteristics resulting from perturbations localized to a brain area strongly associated with autism.