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Development and Innervation of Mechanosensory Hair Cells

Sensorineural hearing loss is an umbrella of diagnoses that encompasses several distinct epidemiologies, including noise, aging, disease, and heredities. It is estimated that 2 to 3 out of every 1000 children are born deaf or hard of hearing in the US, while 8.5% of adults over the age of 55 are found to have disabling hearing loss. In a developmental setting, hearing loss can be a result of improper development of the sound-detecting mechanosensory hair cells, improper innervation of hair cells or improper synapse formation. In the auditory system mechanosensory hair cells are activated by sound and convert this mechanical stimulation into an electrical signal (action potential) for the central nervous system. In zebrafish, mechanosensory hair cells are additionally found in another sensory system, the lateral line system, which is important for prey and predator detection as well as alignment against flow. The hair cells of the lateral line system are conveniently located on the body surface (and not in the bony cochlea), thus making zebrafish an ideal model organism for studying hair cell development and innervation.

Development of Neurons that Integrate Multisensory Input

A major task of the central nervous system is to make sense of the environment and mount an appropriate reaction or response. In humans the inability to integrate sensory input is apparent in disorders such as Autism and Dyslexia. For animals, the ability to organize and integrate inputs from different sensory systems is critical for capturing pray, escaping predators, etc. We are using optogenetic techniques to identify neurons with multisensory integration capabilities and study their development. Larval zebrafish are becoming a very appealing model organism for answering questions about neural circuitry formation and sensory input integration for several reasons. At the larval stage of 5 days post fertilization, the nervous system of zebrafish is relatively simple, the larvae have developed all major organ systems, they are free swimming and display different behaviors such as searching for food, escaping threats, swimming against a current etc., which require sensory input integration. We hope that by studying sensory integration in zebrafish we can gain insights on principles of sensory integration in humans and what may go wrong in different disorders.