Award Abstract # 1656574
Neural mechanisms of sleep loss in Mexican cavefish

NSF Org: IOS
Division Of Integrative Organismal Systems
Recipient: FLORIDA ATLANTIC UNIVERSITY
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: FY 2017 = $333,000.00
History of Investigator:
  • Alex Keene (Principal Investigator)
    KeeneA@FAU.edu
Recipient Sponsored Research Office: Florida Atlantic University
777 GLADES RD
BOCA RATON
FL  US  33431-6424
(561)297-0777
Sponsor Congressional District: 22
Primary Place of Performance: Florida Atlantic University
777 Glades Road
Boca Raton
FL  US  33431-6424
Primary Place of Performance
Congressional District:
22
Unique Entity Identifier (UEI): Q266L2NDAVP1
Parent UEI: D4GCCCMXR1H3
NSF Program(s): Modulation
Primary Program Source: 040100 NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 1228, 9178, 9179
Program Element Code(s): 7714
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.074

ABSTRACT

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

Note:  When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

Collie, Joseph and Granela, Odelvys and Brown, Elizabeth B. and Keene, Alex C. "Aggression Is Induced by Resource Limitation in the Monarch Caterpillar" iScience , v.23 , 2020 https://doi.org/10.1016/j.isci.2020.101791 Citation Details
Jaggard, James B. and Lloyd, Evan and Yuiska, Anders and Patch, Adam and Fily, Yaouen and Kowalko, Johanna E. and Appelbaum, Lior and Duboue, Erik R. and Keene, Alex C. "Cavefish brain atlases reveal functional and anatomical convergence across independently evolved populations" Science Advances , v.6 , 2020 https://doi.org/10.1126/sciadv.aba3126 Citation Details
McGaugh, Suzanne E. and Passow, Courtney N. and Jaggard, James Brian and Stahl, Bethany A. and Keene, Alex C. "Unique transcriptional signatures of sleep loss across independently evolved cavefish populations" Journal of Experimental Zoology Part B: Molecular and Developmental Evolution , v.334 , 2020 https://doi.org/10.1002/jez.b.22949 Citation Details
Stahl, Bethany A. and Jaggard, James B. and Chin, Jacqueline S.R. and Kowalko, Johanna E. and Keene, Alex C. and Duboué, Erik R. "Manipulation of Gene Function in Mexican Cavefish" Journal of Visualized Experiments , 2019 10.3791/59093 Citation Details
Jaggard, James B. and Lloyd, Evan and Lopatto, Arthur and Duboue, Erik R. and Keene, Alex C. "Automated Measurements of Sleep and Locomotor Activity in Mexican Cavefish" Journal of Visualized Experiments , 2019 10.3791/59198 Citation Details
Paz, Alexandra and Keene, Alex C. "What Can a Blind Fish Teach Us About Sleep?" Frontiers for Young Minds , v.7 , 2019 10.3389/frym.2019.00103 Citation Details
Stahl, Bethany A. and Peuß, Robert and McDole, Brittnee and Kenzior, Alexander and Jaggard, James B. and Gaudenz, Karin and Krishnan, Jaya and McGaugh, Suzanne E. and Duboue, Erik R. and Keene, Alex C. and Rohner, Nicolas "Stable transgenesis in Astyanax mexicanus using the Tol2 transposase system" Developmental Dynamics , v.248 , 2019 10.1002/dvdy.32 Citation Details
Keene, Alex C. and Duboue, Erik R. "The origins and evolution of sleep" The Journal of Experimental Biology , v.221 , 2018 10.1242/jeb.159533 Citation Details
Jaggard, James B and Stahl, Bethany A and Lloyd, Evan and Prober, David A and Duboue, Erik R and Keene, Alex C "Hypocretin underlies the evolution of sleep loss in the Mexican cavefish" eLife , v.7 , 2018 10.7554/eLife.32637 Citation Details
Lloyd, Evan and Olive, Courtney and Stahl, Bethany A. and Jaggard, James B. and Amaral, Paloma and Duboué, Erik R. and Keene, Alex C. "Evolutionary shift towards lateral line dependent prey capture behavior in the blind Mexican cavefish" Developmental Biology , v.441 , 2018 10.1016/j.ydbio.2018.04.027 Citation Details

PROJECT OUTCOMES REPORT

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

Please report errors in award information by writing to: awardsearch@nsf.gov.

Print this page

Back to Top of page