Neuronal Dysfunction in the 15q13.3 Microdeletion Disorder

Abstract

Using a genetic disorder and patient samples, the work in this thesis provides novel insights into the underlying causes of brain and nerve disorders. Patients with this disorder are missing a large amount of genetic material, and can develop disorders such as seizures, autism spectrum disorders, and ADHD and may also fail to achieve general milestones in socialization, growth, learning, and motor development. Because it is dangerous and invasive to access patient brain and nerve samples directly, this project converted patient blood or skin samples into neurons which were then studied. This thesis aimed to achieve three broad objectives. The first was to characterize an excitatory neuron subtype from three different families to identify changes in shape, connectivity, and function. The second objective involved identifying how these neurons might express different gene profiles, and what this means for the mechanisms involved in disease development. The third objective was to investigate a possible mechanism at the molecular level, which might offer insights into future therapies. The totality of the work in this thesis provides new insights into the cellular and molecular bases for disease in the 15q13.3 microdeletion disorder and offers future perspectives on how this disorder and others like it might be investigated and treated in the future.