The Developmental Origins of Resilience Lab (Twitter: @theDOORlab)
During the last century, medicine has made unprecedented progress in the treatment of disease. In contrast, much less focus has been placed on parallel advancement for the prevention of disease. Consequently, the largest current worldwide disease burden comes from preventable mental and physical illnesses, such as depression, anxiety, diabetes, and hypertension. Stressful life events, particularly during critical developmental periods, have been linked to increased risk of virtually all diseases, including metabolic and cardiovascular ones, and a significant effort is underway to understand stress-induced biological consequences. Nevertheless, even in the presence of the most severe stressors, some individuals remain resistant to the development of stress-induced pathology. Identifying the neurobiological basis for this natural resilience can therefore lead to the development of novel preventative strategies aimed at strengthening resiliency circuits.
To tackle the mechanisms for individual variability in stress-responses, the DOOR lab uses several animal models, with the overarching unifying goal of understanding the structure, function, and Developmental Origins Of Resilience. In a mouse model of adult social defeat stress, we dissect preexisting neurocircuit structure-function differences in susceptible versus resilient animals using state-of-the-art tools including in vivo chemogenetics, optogenetics, and miniscope imaging, ex vivo super-resolution imaging of dendritic spines, ex vivo whole-brain imaging of functional or structural connectivity using a variety of genetic and/or viral labeling tools, and graph theoretical analysis of co-activation patterns as a proxy for functional connectomics. In a separate set of experiments, we combine rat early life maternal separation with wireless EEG and/or EKG recordings in dams and their pups. This data is used to understand individual variability in developmental trajectories and the role of dam-pup autonomic synchrony as a potential protective factor. Parallel EKG recordings and synchrony analyses are being conducted during mother-infant interactions in the newborn nursery. Finally, the lab is spearheading a study on wild rat stress-responses, asking the simple question: do depressive-like states occur in the wild, or are they a genetic and environmental epiphenomenon of laboratory breeding?
In addition to answering questions about the neurobiological basis for resilience, the DOOR lab is committed to the development of new tools and to the movement toward #openscience. In collaborative work with two different engineering groups, we are developing novel wireless telemetry devices for wild rats and a robotic solution for ex vivo neuronal microinjections. Recently, we also launched a website, MouseCircuits.org, as an open science repository of chemogenetic and optogenetic circuit dissection.
- Anderson K, Dumitriu D. MouseCircuits.org: An online repository to guide the circuit era of disordered affect. BioRxiv https://doi.org/10.1101/2020.02.17.951608 (submitted, Biol Psych)
- Gozali A, Gibson S, Lipton LR, Pressman AW, Hammond BS, Dumitriu D. Assessing the effectiveness of a pediatrician-led newborn parenting class on maternal newborn-care knowledge, confidence and anxiety: A nonrandomized controlled trial. medRxiv https://doi.org/10.1101/2019.12.18.19014936 (in revision, Early Human Development)
- Parsons MH, Deutsch MA, Dumitriu D, Munshi-South J. Differential responses by urban brown rats (Rattus norvegicus) toward male or female-produced scents in sheltered and high-risk presentations. Journal of Urban Ecology 2019; Sept 17; 5(1) [epub ahead of print]
- Takahashi A, Chung J, Zhang S, Zhang H, Grossman YS, Aleyasin H, Flanigan ME, Pfau ML, Menard C, Dumitriu D, Hodes GE, McEwen BS, Nestler EJ, Han MH, Russo SJ. Establishment of a repeated social defeat stress model in female mice. Scientific Reports 2017; Oct 9; 7(1):12838 PMCID: PMC5634448
- Dumitriu D, Laplant Q, Grossman Y, Dias C, Janssen WG, Morrison JH, Nestler EJ. Subregional, dendritic compartment, and spine subtype specificity in cocaine-regulation of dendritic spines in the nucleus accumbens. J Neurosci 2012; May 16; 32(20):6957-66 PMCID: PMC3360066
- Dumitriu D, Rodriguez A, Morrison JH. High-throughput, detailed, cell-specific neuroanatomy of dendritic spines using microinjection and confocal microscopy. Nat Prot 2011; Aug 25; 6(9): 1391-411 PMCID: PMC3566769
Current Research Support
RISE Award Dumitriu (PI) 06/01/2019-05/30/2021
Title: Novel telemetry for studying wild rats in the wild
In collaboration with Dr. John Kymissis from Electrical Engineering, we will build implantable, peer-to-peer enabled, rechargeable telemetry devices for rats.
R01MH111918 Dumitriu (PI) 09/18/2017-06/30/2022
Title: Multiscale connectomic principles of resilience and susceptibility in mouse
This project investigates individual variability in the structural and functional connectomes associated with divergent stress response in an adult social defeat model.
Completed Research Support
P51OD011107 Carter (PI) 12/01/2018-11/30/2019
Title: California national primate center
This projects seeks to lay the foundation of successful synaptic aging by investigating the molecular profiles of cortical synapses from intact versus cognitively impaired monkeys
Role: PI on subcontract
NIH Pediatric Research LRP Dumitriu (PI) 08/13/2017-08/12/2019
Title: Functional connectome associated with mouse resilience to social stress
The objective of the LRP is to offset educational loan burden for health professionals engaged in research.
Role: LRP Awardee
P01AG16765 Baxter (PI) 03/15/2015-02/28/2017
Title: Estrogen and the aging brain
This PPG investigates the relationship between endocrine status and aging with respect to reproductive
physiology and cognition in both rodent and primate models.
NARSAD Young Investigator Award Dumitriu (PI) 01/15/2015-01/14/2017
Title: Role of circuit-specific cortical synaptic plasticity in driving susceptibility versus resilience to depression
The goal of this study is to elucidate the connectomic and plasticity mechanisms that underlie distinct behavioral outcomes following stress in a mouse social defeat paradigm by looking at cFOS activation patterns and dendritic spine morphology.
F30 MH083402 Dumitriu (PI) 04/04/2008-04/03/2012
Title: Live-Imaging and characterization of estrogen-induced dendritic spines
Ruth L. Kirschstein National Research Service Award to support MSTP training, including salary, supplies, travel.