Issa, FadiErickson, TimothyVenuto, Alexandra2023-09-142023-072023-07-21July 2023http://hdl.handle.net/10342/13169The lateral line is a hair cell-based sensory system that is important for multisensory behaviors like schooling, rheotaxis, and predator/prey detection in aquatic vertebrates. This dissertation work uses the first genetic model for the congenital loss of lateral line function in zebrafish. We have found zebrafish ohnologs of a gene required for hair cell function whose mRNA expression patterns are cleanly partitioned between inner ear and lateral line hair cell populations. Genetic disruption of each ohnolog results in specific loss of either auditory/vestibular function or lateral line function. Since lateral line mutants exhibit normal auditory and vestibular behaviors, we can investigate lateral line-mediated behaviors in developing larval zebrafish. In my second chapter, I develop a repeated treatment timeline using neomycin sulfate to continually ablate the lateral line in early larval zebrafish to compare to the genetic lateral line mutant. I examine hair cell regeneration and proliferation rates, as well as associated toxicity of repeated neomycin treatments in larval zebrafish. In conclusion, I find that low doses of neomycin sulfate treatments every 12 hours in 3-4 day old zebrafish are sufficient to continuously disable lateral line function. In my third chapter, I begin my analysis of these “lateral line-less” fish to investigate the role of the lateral line in modulating expression of the social hormone parathyroid hormone 2. Parathyroid hormone 2 (Pth2) is a vertebrate-specific neuropeptide for which thalamic expression is upregulated by social contact with conspecifics. In this project, I measure pth2 levels in zebrafish mutants lacking hair cell function in either the lateral line only, or in both the inner ear and lateral line. Socially raised lateral line mutants express lower levels of pth2 relative to wild-type siblings, but there is no further reduction when all sensory hair cells are nonfunctional. However, social isolation of hair cell mutants causes a further reduction in pth2 expression, pointing to additional unidentified sensory cues that influence pth2 production. Lastly, I report that social context modulates fluorescent transgenes driven by the pth2 promoter. Altogether, these data suggest that lateral line mutants experience a form of isolation, even when raised socially. In my fourth chapter, I characterize a novel swim bladder over-inflation phenotype associated with the lateral line mutants. Larval zebrafish achieve neutral buoyancy between 3-4 days post-fertilization by gulping air from the water’s surface to inflate their swim bladders. We define this behavior of swimming to the air-water interface as “surfacing.” Little is known about the sensory basis for this underappreciated behavior of larval fish. I observe that approximately half of lateral line mutants over-inflate their swim bladder during initial inflation and become positively buoyant. Thus, I hypothesize that larval zebrafish use their lateral line to sense the air-water interface during the surfacing behavior to regulate swim bladder inflation. I report that (i) over-inflation is caused by abnormal surfacing behaviors in lateral line mutants, (ii) lateral line defects are responsible for swim bladder over-inflation, and (iii) the lateral line is specifically responsible for surface detection during initial inflation. In summary, I reveal a novel sensory basis for achieving neutral buoyancy where larval zebrafish use their lateral line to sense the air-water interface and regulate initial swim bladder inflation. In my fifth chapter, I characterize surfacing as a multi-sensory behavior that involves photosensory and chemosensory cues in addition to mechanosensory cues. Only half of lateral line mutants over-inflate their swim bladder, so I hypothesize that other sensory systems, like photosensory cues, help larvae to properly perform the surfacing behavior for initial swim bladder inflation. In this chapter, I use a combination of genetic and environmental manipulations to investigate the roles of ocular and non-ocular photosensation, social isolation, and chemosensory cues on initial swim bladder inflation in the context of genetic loss of lateral line function. Overall, I find that initial swim bladder inflation in larval zebrafish is affected by non-ocular photosensory and chemosensory cues when larvae are genetically deprived of both visual and lateral line sensation.application/pdfenlateral linezebrafishswim bladdermultisensorybehaviorneurobiologysensory systemsneuroethologysurfacingswim-upDoctoral Dissertation2023-09-12