Central auditory pathways for integrating auditory input with head position during active sound localization in mice

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Hearing and balance disorders are widespread in the US and can cause psychological distress and impaired movement. Active sound localization, or moving the head while listening, is an example of a behavior that integrates auditory input from both ears with input about head position (NIDCD Priority Area 1: Perception). Indeed, people with single-sided hearing loss or cochlear implants can use head motion to compensate for disordered auditory input. Understanding how central auditory pathways integrate auditory input with head position signals would help us study how people can behaviorally and neurally adapt to and cope with vestibular and auditory disorders. A mouse model of active sound localization would advance our understanding of the neural circuitry of active sound localization. Mice naturally rely on hearing to find sound sources, such as seeking out their lost pups by the sound of their cries. Moreover, there is a powerful toolkit of genetic, physiological, and imaging tools available to dissect neural circuit function in mice. Despite all these advantages, there are no models of active sound localization in mice. This project will fill that gap. The specific objective of this proposal is to determine how mice align their heads with sound in order to localize it. My hypothesis is that auditory cortex integrates auditory input with head position signals to enable this behavior. The central innovation of this proposal is to unite large-scale neural recordings with high- resolution analysis of free behavior, enabling me to understand how activity in populations of neurons mediates adaptive behavioral responses. In Aim 1, I will identify the strategies and brain regions that mice use to align their heads with sound. In Aim 2, I will determine how neurons in the auditory cortex encode head motion and integrate it with sound. Collectively, these studies will elucidate the neural circuitry that enables active sound localization, and lay the groundwork for future work to understand how this circuitry confers resilience to hearing loss. I will perform this research at Emory University, a leading R1 research institution with an interactive neuroscience community and abundant intellectual and technical resources. I am a tenure-track Assistant Professor at Emory, with my own independent lab space and equipment. I have hired a full-time research specialist to assist in these studies, and I am able to train graduate students from Neuroscience, Biomedical Engineering, and the MD/PhD program. I will receive guidance from two consultants: Dr. Robert Froemke at New York University and Dr. Robert Liu at Emory. Both are experts in auditory physiology and behavior. This support will empower me to direct an independent research program on the distributed processing in auditory pathways that direct natural behavior and confer resilience to disorder.