The superior colliculus (SC) plays a critical role in integrating visual and auditory inputs to assess saliency and promote action. However, the underlying cell types and circuitry used to encode multimodal information and the mechanisms used during development to form the circuitry remain largely unknown. The recent explosion of new technology in mouse genetics allows neurons and circuits to be manipulated and specific genes to be removed, but surprisingly, the mouse has not yet been shown to be a model to study sensory integration. The overall objective of this proposal is to determine the functional properties of visual/auditory multisensory neurons in the mouse SC, to determine how these properties change in a mouse line genetically engineered to test hypotheses about how these properties develop. The central hypothesis to be tested is that visual and auditory information converge in the mouse SC to create multimodal neurons that form a multimodal map of space, and that map alignment forms using a visual map template-matching mechanism. The goal of Specific Aim 1 is to identify, and determine the response properties of, mouse SC visual/auditory multimodal neurons. To accomplish this, awake, head-fixed mice, allowed to freely run on a treadmill, will be stimulated with spatially/temporally/spectrally restricted visual and auditory stimuli while the SC neuronal response properties are being recorded using high-density silicon probes. The SC neural activity of ~170 neurons will be simultaneously recorded from in each mouse, using high-density silicon probes. Data analysis will determine the spatiotemporal receptive fields of the visual, auditory and visual/auditory multimodal neurons, their sensory integration properties, and the spatial/temporal/spectral components of the stimulus needed to elicit integration. Innovations include the use of virtual auditory space stimuli to present localized sound, and the recording and data analysis methods used. Experiments proposed in Specific Aim 2 will test the longstanding hypothesis that the alignment and integration of the visual and auditory inputs in the SC form using the visual map as a template. The approach will be to record and analyze the auditory and visual response properties as in Aim 1 but from transgenic mice engineered to have a duplicated visual map in the SC, and determine if the auditory map rearranges to align and integrate with the duplicated visual map. The proposed research is significant because it will provide the first comprehensive analysis of the receptive field properties of visual/auditory integrative neurons in the mouse SC, and will determine the general principles of how these properties develop. The results of this work can be exploited immediately and in the future, to determine the underlying circuitry used to integrate sensory information, the specific cell types involved, and how the state of the animal modulates these properties.
The proposed research is relevant to public health because the integration of information coming from different sensory modalities is a fundamental brain function, and sensory integration deficits are known symptoms of people with autism, schizophrenia, and other neuro- developmental disorders. The goal of this research plan is to determine how visual and auditory information is combined in the mouse superior colliculus, a midbrain sensory integrative structure. The findings will provide the fundamental knowledge that will enable research to better understand and treat disorders of sensory integration.