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.
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
Brain-wide dissection of stress
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
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:
R21NS105071-01A1 PI: Keene, A.C.; co-PI: Duboue, 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
R15MH118625-01 PI: Duboue, E.R. 09/24/2018 - 09/23/2021
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.
NSF 1923372 PI: Duboue, E.R. 09/01/2019 - 08/31/2022
EDGE CT: NSF-BSF: Functional Genotype-Phenotype Mapping in the Mexican Blind Cavefish, Astyanax mexicanus.
The goal of the project is to develop genetic and transgenic tools for the blind Mexican cavefish, Astyanax mexicanus and their surface dwelling conspecifics. This award is also funding an Astyanax stock center, as well as various outreach programs including the Research Diaries podcast. This award is a collaboration (co-PIs) with Johanna Kowalko and Alex Keene (FAU), Suzanne McGaugh (University of Minnesota), Nicholas Rohner (Stowers) and Lior Appelbaum (Bar-Ilan, BSF Collaborator).
FAU Internal Award. PI: Duboue, E.R. and Gothilf, Y. 03/01/2020 - 02/28/2021
Dissection of Genetic and Neuronal systems modulating stress-induced hypophagia
This is a pilot award from FAU Division of Research. This will fund pilot experiments to examine how stress and feeding interact at a genetic and molecular level. This project uses an early life stress model in zebrafish, and examines the role of AgRP using lines generated and maintained by the Gothilf lab.
BSF 2019262 PI: Duboue, E.R. and Gothilf, Y. 06/15/2020 - 06/14/2024
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).