Developmental mechanisms underlying visual and auditory topographic map alignment and accurate spatial orienting behavior

Across species, multisensory integration (MSI) is used to accurately and rapidly localize objects in the environment. This process is presumed to rely on the correct organization of sensory inputs into topographically aligned maps of egocentric space. However this idea has not been rigorously tested. MSI and spatial orienting behaviors are compromised in many developmental disorders including Autism, Schizophrenia and ADHD, highlighting the significance of understanding the developmental mechanisms that establish effective MSI-dependent behaviors. The overall objective of this application is to determine the mechanisms used to integrate visual and auditory maps of location in the mouse superior colliculus (SC) and identify the behavioral consequences to animals deficient in these mechanisms. The central hypothesis is that sensory experience is used to align auditory and visual maps of space in the SC; furthermore, accurate alignment of the two maps is required for effective MSI and robust natural spatial orienting behavior. Aim 1 seeks to determine both the developmental window in which MSI forms and the critical period of sensory influence. We will present a wake mice with spatially restricted visual and auditory stimuli while recording neuronal responses in the SC using high-density probes. Analyzing this data will determine the spatial receptive fields (RFs) of visual, auditory and visual/auditory multimodal neurons. This will be done at key developmental stages plus or minus visual or auditory deprivation. The goal of Aim 2 is to quantify how developmental changes in multisensory experience alter natural stimulus localization behaviors. Mice innately hunt insects and their ability to capture them is most efficient when they have access to multisensory cues. Of note, orienting behavior during prey capture is disrupted in mouse models of ASD. Prey capture behaviors such as time to cricket detection, spatial accuracy and precision of pursuit, and time to capture success will be measured in mice at different ages and in those deprived of early vision or audition. This aim will reveal the role that sensory experience plays in generating natural localization behavior. Experiments in Aim 3 will test the longstanding hypothesis that the alignment and integration of visual and auditory inputs in the SC rely on the visual map as a template. We will record the auditory and visual response properties as in Aim 1 from two populations of mice: those with scrambled or duplicated visual map topography via perturbations in EphA/ephrin-A signaling or shifted via prism goggles. We can then determine if the auditory map rearranges to align and integrate with the duplicated, scrambled or shifted visual map and, if so, how these changes lead to altered orienting behavior during prey capture.