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Neural functions rely on highly ordered circuit assembly during development. In the central auditory system, these connections must be very precise to allow for the fast and reliable processing needed in auditory perception. Our laboratory studies the development and plasticity of auditory brainstem circuits needed to localize sounds. We are interested in discovering the mechanisms that guide auditory axons to their correct synaptic targets and form specialized synapses. We are currently investigating this in three lines of research.

Glial cells in auditory circuit formation. We are studying the contributions of glial cells, including astrocytes and microglia, to synapse formation and maturation in the auditory pathways. We have found that astrocytes are important for the formation of inhibitory synapses and for the formation of mature dendritic arbors. We are now exploring how microglia contribute to synapse formation and synaptic pruning in the auditory brainstem, and how these roles contribute to auditory function. These studies highlight the importance of cellular communication between neurons and glia during development.

Caspase-3 in auditory brainstem development. While it is well-established that caspase-3 is an effector of cell death, studies have suggested additional roles in development. We found that active (cleaved) caspase-3 displays an intriguing expression pattern along the auditory pathway during development. It is initially seen in auditory nerve axons projecting centrally. Expression seems to shift to sequentially higher levels of auditory centers. Notably, transitions in expression occur at about the time synapses form between transition areas. When caspase-3 was inhibited during development, we observed significant axon targeting errors and defects in formation of auditory centers. Caspases are proteases that cleave other proteins. We are currently exploring which proteins are caspase-3 substrates during development and how they act to shape auditory circuits.

Auditory brainstem dysfunction in neurodevelopmental disorders. Fragile X syndrome (FXS), a neurodevelopmental disorder associated with intellectual disability, is also frequently associated with hyperacusis, the perception that sounds of normal intensity are uncomfortably or painfully loud. We have explored how impaired auditory brainstem development might contribute to hyperacusis in FXS.