Publications

The inclusion of microexons by alternative splicing occurs frequently in neuronal proteins. The roles of these sequences are largely unknown, and changes in their degree of inclusion are associated with neurodevelopmental disorders1. We have previously shown that decreased inclusion of a 24-nucleotide neuron-specific microexon in CPEB4, a RNA-binding protein that regulates translation through cytoplasmic changes in poly(A) tail length, is linked to idiopathic autism spectrum disorder (ASD)2. Why this microexon is required and how small changes in its degree of inclusion have a dominant-negative effect on the expression of ASD-linked genes is unclear. Here we show that neuronal CPEB4 forms condensates that dissolve after depolarization, a transition associated with a switch from translational repression to activation. Heterotypic interactions between the microexon and a cluster of histidine residues prevent the irreversible aggregation of CPEB4 by competing with homotypic interactions between histidine clusters. We conclude that the microexon is required in neuronal CPEB4 to preserve the reversible regulation of CPEB4-mediated gene expression in response to neuronal stimulation.

JTD Keywords: Alternative splicing, Animals, Autism spectrum disorder, Cpeb4 protein, human, Cpeb4 protein, mouse, Exons, Gene expression regulation, Humans, Mice, Neurons, Protein aggregates, Protein biosynthesis, Rna-binding proteins

Autism is a neurodevelopmental disorder characterized by deficits in social communication and repetitive patterns of behavior. Individuals affected by Autism Spectrum Disorder (ASD) may face overwhelming sensory hypersensitivities that hamper their everyday life. In order to promote awareness about neurodiversity among the neurotypical population, we have developed an interactive virtual reality simulation to experience the oversensory stimulation that an individual with autism spectrum disorder may experience in a natural environment. In this experience, we project the user in a first-person perspective in a classroom where a teacher is presenting a lecture. As the user explores the classroom and attends the lecture, he/she is confronted with sensory distortions which are commonly experienced by persons with ASD. We provide the users with a virtual reality headset with motion tracking, two wireless controllers for interaction, and a wristband for physiological data acquisition to create a closed feedback loop. This wearable device measures blood volume pulse (BVP) and electrodermal activity (EDA), which we use to perform online estimations of the arousal levels of users as they respond to the virtual stimuli. We use this information to modulate the intensity of auditory and visual stimuli simulating a vicious cycle in which increased arousal translates into increased oversensory stimulation. Here, we present the architecture and technical implementation of this system.

JTD Keywords: autism spectrum disorder, neurodiversity, physiology, Autism, Autism spectrum disorder, Neurodiversity, Physiology, Virtual reality