DUBOUE LAB
RESEARCH
Overview
Stress responses are conserved reactions that ensure survival in the face of danger. These reactions are complex, and are driven by the dynamic interaction of neuronal populations through-out the brain. How the brain drives normal stress behaviors is not fully understood. Moreover, it is unclear how subtle changes to neuronal structure or function underly differences in stress, as in patients with anxiety disorders, or across evolution. We use small fish models to address these questions.
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Larval fish are transparent and exhibit robust stress responses, including changes in behavior and production of the stress hormone, cortisol. Moreover, the entire brain of larvae is comprised of roughly 100,000 neurons, and neural activity can be visualized and recorded brain wide in a living animal as it interacts with the environment. We use this system to examine how the brain drives stress, and how these circuits are altered in anxiety disorders, or across evolution
Stress is driven by brain-wide changes in neural activity.The small size of fish permits visualization of the entire central nervous system in a living organism
Movie of the entire brain of a 5 day old zebrafish expressing a genetically encoded calcium indicator in all neurons. Image acquired using two-photon imaging
Specific Projects
Brain-wide dissection of stress​
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Stress is homeostatic: the presentation of an aversive cue causes changes in behavior and physiology yet, after the threat is no longer present, the brain actively restores base-line states. We are using volumetric, two-photon imaging of neural activity to identify populations that are involved in both the activation of stress responses and recovery from that initial reaction.
Confocal image of the dorsal habenulae (dHb) of a larval zebrafish. We find that the dHb has a critical role in recovery from stress. Taken from Duboue et al. (2017)
A zebrafish model of early life stress
Childhood trauma can result in life-long issues with anxiety and substance abuse, yet how early life stress impacts the developing brain is not fully understood. We find that zebafish subjected to chronic stress at larval stages have increased stress in juvenile or adult stages. We also find ELS animals are hyperphagic, and have broken sleep. Using genetic tools unique to zebrafish and volumetric imaging, we are examining how early life stress impacts the developing brain, resulting in behavioral dysfunction.
Evolution of stress responses using the Mexican blind cavefish
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Stress responses are found in all animals, yet the timing and degree of these responses varies considerable. How stress circuits change over evolutionary time is poorly understood. We find that cave-dwelling forms of the blind Mexican cavefish have diminished stress responses compared to their eyed surface dwelling conspecifics. Using genetic technology generated in our and our collaborators labs, we are exploring how stress circuits differ between these two different populations of fish.
FUNDING AND SUPPORT
Our lab is currently funded through support from the National Institutes of Health, the National Science Foundation, the Binational Science Foundation, FAU's Division of Research, and from the Jupiter Life Science Initiative. The active grants in our lab are:
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5T34GM136486-03 PI: Duboué, ER, co-PI Murphy, Fraizer 04/2020 – 03/2025
U-RISE at Florida Atlantic University
This is a program grant that is aimed at giving underrepresented minority students a unique educational experience focused on primary research and prepare them for Graduate School. The program as of Fall 2022 has 12 students.
BSF 2019262 PIs: Duboué, E.R., and Gothilf, Y. 11/2020-10/2025
The effect of early-life stress on the regulation of appetite in zebrafish.
The goal of the project is to understand how neuronal circuits that modulate stress can alter feeding systems. The project uses zebrafish, Danio rerio, and examines the role of AgRP in stress-induced hypophagia. This is a collaboration with Dr. Yoav Gothilf (Tel Aviv University).
NIH 1 R15 MH132057-01 PI: Duboué, ER 10/2022 – 10/2025
Determining the impact of early adversity on the developing vertebrate brain
The goal of this study is to examine how early life stress alters the developing brain in zebrafish. Using a zebrafish model that my lab developed at FAU, we will assess how whole-brain anatomy and function at multiple developmental stages associates with enhanced stress following chronic stress exposure in early larval stages, how hormonal signaling alters the developing brain, and which genetic mechanisms may be contributing to these differences, potential opening therapeutic targets.
Pending
NIH 1R15DK144843 PI: Duboué, E.R. Impact = 20
Decoding the role of naturally occurring variation in genetic and neural regulation of feeding and energy homeostasis.
The goal of this study is to investigate how feeding changes evolve, with a focus on the melanocortin system.
Past Support
NSF1923372 PI: Duboué, E.R. 09/01/2019 – 08/31/2023
EDGE CT: NSF-BSF: Functional Genotype-Phenotype Mapping in the Mexican Blind Cavefish, Astyanax mexicanus
The goal of the project is to develop genetic technology, including tissue-specific transgenic lines and lines with targeted mutations in specific genes, in the blind Mexican cavefish and their surface conspecifics.
NIH R21NS105071-01A1 PI: Keene, A.C.; co-PI: Duboué, E.R. 03/01/2018 - 02/28/2020
Development of genetic tools for functional analysis of sleep in cavefish
The goal of the project is to generate tools for the functional dissection of behaviors, principally sleep, in an emerging model system, the Mexican cavefish. Tools proposed include transgenic technologies, and the development of a brain-wide neuroanatomical atlas in several cavefish populations
FAU-Israeli Pilot Award PI: Duboué, E.R., co-PI: Gothilf, Y. 02/01/2020-01/31/2021
Dissection of the genetic and neuronal systems underlying early life stress-induced hyperphagia
The goal of the project is to elucidate the neuronal modulators of feeding during times of stress. The proposal is a collaboration between the Duboué and Gothilf (Tel Aviv University), and will focus on the effects of a disrupting AgRP-neurons, and on transcription profiling of these neurons during chronic stress.
NIH R15MH118625-01 PI: Duboué, E.R. 09/24/2018 - 09/23/2022
Functional dissection of brain-wide circuits modulating recovery from stress
The goal of the project is to examine a recently identified forebrain to midbrain circuit important for restoring baseline states of behavior and physiology following a stressful event, and to further identify anatomical areas that act upstream and downstream of this identified circuit.
FAU JLSI/iHEALTH SEED PI: Duboué, E.R. and Fontenas, L 01/2024 – 12/2024
Determining evolutionary divergence of glia cells in neuronal processing
The goal of the study is to deduce what changes in glia composition and make up drive differences in behavioral adaptation. The study will focus on the blind cavefish, Astyanax mexicanus as a model, and will use a combination of state of the art imaging, staining of molecularly defined glia subtypes, functional interrogation, and functional imaging.
NIH R13OD036186 PI: Duboué, E.R. (lead), Kowalko, Keene, and Rohner 02/2024-12/2024
Enhancing Diversity at the 8th Astyanax International Meeting (AIM)
This award funded the 8th annual Astyanax International Meeting. The project facilitated collaboration, highlighted recent advances, and promote diversity in the scientific community, with a particular focus on underrepresented groups from Mexico and Latin America.