Subterranean Fishes of the World

4317

2019

AIM 2019

67

Animals are highly tuned to sense changes in both internal and external environments and adapt their behavior accordingly. Hungry animals reduce sleep, increase foraging behavior, and prefer high-calorie foods. Our lab is primarily focused on understanding the genetic basis of this shift in behavioral choice, and how these interactions evolve in response to environmental perturbation. We are currently using the fruit fly, Drosophila melanogaster, to identify genes and neural circuits that are required for metabolic regulation of sleep. Flies, like mammals, suppress sleep when starved, providing a system to interrogate interactions between sleep and metabolism. We performed a large scale screen to identify novel regulators of sleep-metabolism interactions and are currently investigating the genes and neural circuits that integrate these processes. We identified a single pair of neurons within the fly brain that are active during starvation, and have demonstrated that they are required for starvation-induced sleep suppression. These neurons express the neuromodulator Leucokinin and regulate the activity of insulin secretion from neuroendocrine cells within the fly brain. Together, the identification of this neural circuit provides a system to investigate the molecular basis for metabolic regulation of sleep with single-cell resolution. Dietary regulation of sleep also requires communication between neurons and nonneural cell-types. We have identified a critical role a number of other cell-types, including glia that also regulate extracellular levels of amino acids, suggesting communication between neurons and glial cells is a critical factor in sleep regulation. In addition, we have performed a genetic screen in non-neuronal tissue, and have identified genetic factors that function in the fat body, the primary site of energy stores, to modulate sleep. The identification of these factors reveals complex brain-periphery communication that regulates sleep. While genetic regulators of sleep have been identified, surprisingly little is known about how sleep evolves, or the reasons for dramatic differences in sleep duration between different species. We have characterized the convergent evolution of sleep loss in multiple populations of the Mexican cavefish, Astyanax mexicanus, that exist as eyed-surface populations that inhabit the rivers of northeast Mexico and blind populations of the same species that inhabit nutrient poor cave environments. We have identified a number of neuromodulators that contribute to the evolution of sleep loss in A. mexicanus cavefish including upregulation of the wake promoting neuropeptide implicated in human narcolepsy Hypocretin/Orexin. In addition, we have developed transgenic methodology in this emergent model system allowing for systematic investigation of the genes and neurons regulating evolved differences in sleep. Investigating the mechanisms of sleep loss in Mexican cavefish has potential to provide insights into the variation in sleep need throughout the animal kingdom, and even between humans.

1

Astyanax Interrnational Meeting