| NSF Org: |
IOS Division Of Integrative Organismal Systems |
| Recipient: |
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| Initial Amendment Date: | August 4, 2017 |
| Latest Amendment Date: | August 4, 2017 |
| Award Number: | 1656574 |
| Award Instrument: | Standard Grant |
| Program Manager: |
John Godwin
IOS Division Of Integrative Organismal Systems BIO Direct For Biological Sciences |
| Start Date: | September 1, 2017 |
| End Date: | February 28, 2021 (Estimated) |
| Total Intended Award Amount: | $333,000.00 |
| Total Awarded Amount to Date: | $333,000.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
777 GLADES RD BOCA RATON FL US 33431-6424 (561)297-0777 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
777 Glades Road Boca Raton FL US 33431-6424 |
| Primary Place of Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | Modulation |
| Primary Program Source: |
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| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
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General Abstract
While sleep is nearly universal in the animal kingdom, the biological factors regulating sleep remain unclear. Sleep duration varies greatly between individuals, but little is known about how variation in brain chemistry may underlie differences in sleep need. To learn more about how brain chemistry affects sleep need, a group of fish that have lost the need to sleep during their evolution are being studied. Mexican cavefish were trapped in caves millions of years ago, and have since adapted to these nutrient-poor environments by dramatically reducing sleep, though we do not yet know what changes in the brain make that possible. Work in this project tests if changes in sleep need are associated with alterations sensory processes that promote the production of a chemical called Orexin. Orexin production in the brain is being compared between cavefish and related, river-dwelling surface fish with regular sleep patterns, and the ability of drugs that influence Orexin to alter sleep in cavefish is also being examined. Determining the chemical basis for sleep loss in Mexican cavefish will enable us to better understand how the brain normally regulates sleep, as well as how changes in brain chemistry, across evolutionary time or day-to-day in animals that need sleep, affect this critical life function and an animal's well-being. Numerous undergraduates from diverse racial and socioeconomic groups will participate in this work, as well as in developing community outreach programs that will use enhance scientific literacy in the public at large and in senior citizen communities in particular.
Technical Abstract
Sleep is a nearly ubiquitous behavior throughout the animal kingdom, yet little is known about the functional and evolutionary principles driving sleep differences between species or individuals within a population. The Mexican cavefish Astyanax mexicanus, exists as independent populations of an ancestral eyed surface morph and blind cave morphs of the same species. The convergent evolution of sleep loss in multiple independent A. mexicanus cave populations provides the unique opportunity to examine the role of ecology and evolutionary history in shaping sleep. This research program will determine whether sensory input through the lateral line directly modulates function of the wake-promoting neuropeptide Orexin and the contributions of changes in Orexin neuroanatomy to the evolution of sleep loss in cave populations. Work produced in this project will contribute to our understanding of the biological basis of sleep with potential extension to a better understanding of the mechanistic basis of naturally occurring sleep differences in humans. In addition to contributing to scientific knowledge across life disciplines, this project will provide opportunities for student training and outreach in the local community. Teaching tools will be developed in collaboration with a local high school to expose students to behavioral ecology and neuroscience research. All developed lab protocols will be made available online for access and use at other high schools and teaching institutions. Additionally, this project will fund students enrolled in programs for first generation and minority college students to work in the research laboratory.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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PROJECT OUTCOMES REPORT
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Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
This project resulted in the identification of the neuropeptide Hypocretin as regulating evolved differences in sleep across cavefish populations. Multiple cavefish populations evolved to have elevated levels of Hypocretin which was associated with shortened sleep. Hypocretin levels are regulated by the lateral line, a sensory organ that detects water flow. Ablation of the lateral line, or inhibition of Hypocretin restored sleep to cavefish. To functionally manipulate sleep-regulating neurons, this project pursed implementing transgenesis in cavefish. Multiple transgenic lines were generated that were then used to label neural circuits and quantify neuronal activity. This approach was used to genetically silence Hypocretin neurons, which restored sleep in cavefish. Taken together, these studies establish cavefish as a model to investigate how sleep differences evolve, and genetic variation in sleep between individuals. The genetic tools developed in this project can be broadly applied to examine traits that differ between surface and cavefish populations. This laboratory research was complemented by the development of numerous outreach activites including the development of virtual laboratories that center around analysis of behavioral data and a 'cavefish livecam' that allows for real time comparisons of behavior in cavefish and surface fish. In addition, the project provided numerous research opportunities for trainees at all levels.
Last Modified: 07/02/2021
Modified by: Alex C Keene
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