The perception of vestibulo-auditory stimuli is controlled by both ascending afferent neurons from primary sensory organs, and descending modulatory efferent neurons from the brain. For over two decades we have known that efferents that release dopamine (DA) innervate vestibulo-auditory organs, yet the influence of DA on the primary mechanosensory cells-hair cells-is poorly understood. Zebrafish have many technical characteristics that make them uniquely suited to study neuronal circuits, including genetic tractability, high fecundity, transparency, low cell number, and superficial hair cells which all support excellent in vivo imaging and electrophysiology. I will use the zebrafish posterior lateral line (pLL) organ as a model for vertebrate vestibulo-auditory systems to understand the dopaminergic efferent circuit. The pLL is composed of neuromasts: islands of only ~12 hair cells that sense hydrodynamics, analogous to cells of the inner ear that are activated by movement of endolymph. Dopaminergic neurons that innervate the ear and pLL of zebrafish originate in the hypothalamus, an organ that regulates homeostasis, sleep, and circadian rhythms. The experiments in this proposal are designed to elucidate how DA modulates hair cells. Based on preliminary data, I hypothesize that the hypothalamus modulates the sensitivity of zebrafish to vestibulo-auditory stimuli by activating excitatory DA receptors expressed by hair cells. Results from these experiments will substantially contribute to our understanding of how the central nervous system can control perception of sensory stimuli by directly modulating primary sensory cells.
Proper sensation of sound is important for accurately understanding the environment. Changes in sound perception that are the result of brain dysfunction, as can occur in post-traumatic stress disorder and schizophrenia, can be debilitating. The results of experiments proposed in this grant will contribute to our understanding of how the neurotransmitter dopamine modulates the perception of sound.