DUBOUE LAB
RESEARCH
Overview
Our lab studies how the brain generates behavior by examining whole-brain mechanisms and the natural variation that shapes them. We are broadly interested in how neural circuits change in both psychological and neurological disorders, as well as how evolution sculpts behavior across species. To do this, we use fish models, which offer rich behavioral repertoires and optically accessible brains at early stages. Zebrafish allow us to uncover fundamental mechanisms of disease and pathology, while Mexican cavefish provide a powerful system for understanding how evolution drives differences in brain structure, function, and behavior. Through this combined approach, we aim to reveal how complex behaviors arise and how they vary across individuals, populations, and species.
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
A zebrafish model of early life stress
Our lab investigates how early life adversity alters the development and long-term function of the vertebrate brain, with a focus on identifying the genetic, hormonal, and neural mechanisms that link early experiences to adult behavior. Using zebrafish—an ideal system for whole-brain imaging, genetic manipulation, and high-throughput behavioral analysis—we developed a model of early life stress (ELS) that exposes larvae to unpredictable mild stressors during specific developmental windows. This approach allows us to examine how stress during sensitive periods shapes the maturation of the neuroendocrine stress axis, glucocorticoid signaling, and brain-wide circuits that regulate emotion and anxiety. The central goal, outlined in our NIH grant is to uncover how ELA disrupts hormonal regulation, gene expression, and neuronal activity across development, and to identify conserved pathways that may explain why childhood adversity has such profound and lasting effects in humans.
Our recent work demonstrates that zebrafish subjected to chronic and unpredictable stress early in life develop long-lasting increases in anxiety-like behavior, elevated baseline cortisol, and dysregulated glucocorticoid receptor signaling. In our recent study, we showed that these effects depend on a precise developmental “critical window”, between 4–6 days post-fertilization, when the stress axis first becomes functional. Stress during this window leads to persistent changes in behavior months later, accompanied by increased basal cortisol levels and upregulation of glucocorticoid and mineralocorticoid receptor transcripts in the brain. Together, these findings position zebrafish as a powerful vertebrate system for uncovering how early adversity becomes biologically “embedded” in the brain and for identifying mechanisms relevant to anxiety, PTSD, and stress-related disorders.
Evolution of stress responses using the Mexican blind cavefish
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Our lab uses the blind Mexican cavefish (Astyanax mexicanus) as a powerful evolutionary model to uncover how natural genetic variation shapes brain function and behavior. Astyanax exists as multiple independently evolved cave populations—each displaying dramatic differences in morphology, sensory structure, and behavior compared to surface fish. This unique system allows us to study evolution in real time and to dissect how complex behaviors emerge, change, and diversify through genetic and neural modifications. Over the past decade, our work has shown that cavefish exhibit robust and heritable differences in sleep, stress responses, feeding behavior, light avoidance, sensory processing, and metabolic regulation, making them an unparalleled vertebrate model for connecting evolution, brain circuits, and behavior.
A central contribution of our lab has been building the modern genetic and neurobiological toolkit that now defines the Astyanax field. In collaboration with long-standing partners—Alex Keene (Texas A&M), Johanna Kowalko (Lehigh), Suzanne McGaugh (University of Minnesota), and Nicolas Rohner (University of Münster)—we establish many of the methods that are now standard: CRISPR/Cas9 mutagenesis; transgenesis pipelines; whole-brain functional imaging; computational brain atlases; quantitative mapping of neural activity; high-throughput behavior tracking; and allele-swap strategies to test the functional impact of naturally occurring genetic variants. These tools allow us to move seamlessly from gene to circuit to behavior—bridging molecular evolution with systems neuroscience.
Our current work focuses on identifying the neural and genetic mechanisms that give rise to evolved behavioral differences, particularly in simple, deeply conserved circuits such as light sensing and feeding pathways. Recent studies (e.g., Kozol et al., 2024) demonstrate that cave populations have rewired early sensory and hypothalamic circuits in ways that reshape attention, arousal, and circuit-level integration. Ongoing work supported by our NIH award leverages allele-swapping and brain-wide imaging to dissect how evolutionary changes in melanocortin receptors (MC3R and MC4R) alter feeding behavior and metabolic state. By pairing powerful genetic tools with whole-brain analysis, we aim to reveal how evolution assembles, modifies, and repurposes conserved neural circuits to generate behavioral diversity.
Together, these efforts position our lab—and the Astyanax model—as a leading platform for understanding how brains evolve, how behavior emerges from genetic variation, and how simple circuit changes can produce profound differences in survival strategies, physiology, and disease vulnerability.
FUNDING AND SUPPORT
Current Funding
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NIH 1R15DK144843 PI: Duboué, E.R. 10/1/2025-9/30/2028
Decoding the role of naturally occurring variation in genetic and neural regulation of feeding and energy homeostasis.
Total award amount = $559,918 (all to FAU)
The goal of this study is to investigate how feeding changes evolve, with a focus on the melanocortin system.
NIH 1R15MH132057 PI: Duboué, ER 10/2022 – 10/2025
Determining the impact of early adversity on the developing vertebrate brain
Total Award Amount = $457,500 (all to FAU)
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.
Past Support
NIH 5T34GM136486 PI: Duboué, ER, co-PI Murphy, Fraizer 04/2020 – 03/2025
U-RISE at Florida Atlantic University
Total Award amount = $1,193,954 (all to FAU)
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 mentored and funded a total of 22 students.
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
Total award amount = $1,148,464 (approximately 25% to FAU)
The goal of the project was 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
Total award amount = $399,509 (all to FAU)
The goal of the project was to generate tools for the functional dissection of behaviors, principally sleep, in an emerging model system, the Mexican cavefish. Tools proposed included 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
Total Award amount = $25,0000, all to FAU
The goal of the project was 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
Total award amount = $445,794 (all to FAU)
The goal of the project was 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
Total Award amount = $20,000 (all to FAU)
The goal of the study was 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)
Total award amount = $5,000 (all to FAU)
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.
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.
Total award amount = $320,000 ($160,000 to FAU)
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).