Comparing Audiovisual Neural Signals Across Environments and Disease-Models

To form representations of the world, brains combine information across sensory modalities. Audiovisual integration, combining auditory and visual information, is an extensively studied example of this process, in part because atypical audiovisual integration is linked to cognitive conditions including schizophrenia and autism spectrum disorder (ASD). However, recent rodent studies are conflicted regarding the regions and mechanisms of audiovisual integration, and this may derive from changes in neural processing caused by different experimental environments: head-fixed or free-movement. Technical challenges in stimulus delivery and longitudinal recording have prohibited neural recordings in the same animals across these conditions. Consequently, because mouse disease-models rarely tolerate head-fixation, they have not been used to test audiovisual hypotheses generated through clinical studies in humans. In this project, I will overcome these hurdles with the host lab, using a novel audiovisual arena I developed to present controlled stimuli to freely-moving mice. First, using wild-type (WT) mice, I will determine the impact of head-fixation versus free-movement on basic audiovisual processing using the host lab’s electrophysiology implant to track neurons for months. Second, I will compare these WT data with recordings from a freely-moving ASD mouse model, to test the hypothesis that ASD presents with excessive audiovisual integration. Finally, I will compare WT and ASD neural responses in mice learning spatial audiovisual reward-association to determine whether differences in passive audiovisual processing correspond to changes in learning. This project represents the first characterization of environment-dependent audiovisual processing, and the first extension of audiovisual integration to a mouse disease-model. The results will therefore be of broad interest across behavioural neuroscience, and promise to boost translational and clinical research efforts.