Development of hemispheric specializations during Auditory Cortex critical periods

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Project Summary Although the organization of the neocortex includes many consistent patterns of connections between cells, individual cortical areas also contain unique circuit-motifs that enable them to perform specific functions. One such specialization is left-hemisphere language dominance, which is well known in humans. Mice and other mammals also use vocalizations for social and reproductive interactions and show hemispheric asymmetry in processing these vocalizations. This similarity suggests there may be shared mechanisms for vocal processing that can be studied using the powerful circuit analysis tools available in animal models. This proposal focuses on the mouse auditory cortex, which preferentially responds to particular sound combinations across frequencies and time, in a context-dependent fashion, and thus encodes important components of species-specific vocalizations. Our work has revealed connectivity differences between the left and right auditory cortices that are hearing-experience dependent, but it is unknown how these differences arise. The long-term goal of this laboratory is to identify specialized circuit features in the auditory cortex that underlie the ability to encode information that is important for social communication and how they go awry in neurodevelopmental communication disorders. The overall objective of this proposal is to identify hemispheric differences in the timing of critical periods, and emergence of the behavioral relevance of lateralized processing. This proposal will test the working hypothesis that hemispheric specializations in auditory processing arise from differences in the maturation rate between the left and right auditory cortices. Maturational differences will be identified through hemispheric comparison of molecular markers related to the onset and closure of critical periods, and circuit- motif development using electrophysiology. We will also identify differences in the emergence of lateralized function with behavioral assays. Preliminary data in this proposal demonstrate significant differences in the maturation rate between the left and right auditory cortices. This approach is innovative because it is the first study to dissect hemispheric differences at the circuitry and functional level in the auditory cortex, and test a novel hypothesis of its origin. The research proposed here is significant because it is expected to reveal fundamental insights into the development of specializations in auditory cortical function, which will provide powerful tools to study how the auditory cortex encodes communication sounds and how this encoding goes awry in neurodevelopmental disorders.