Brain-wide Electrical Spatiotemporal Dynamics Encode Depression Vulnerability
Open accessAbstract
Brain-wide fluctuations in local field potential oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors would provide fundamental insights into how the brain signals emotional pathology. Using machine learning, we discover a spatiotemporal dynamic network that predicts the emergence of major depressive disorder (MDD)-related behavioral dysfunction in mice subjected to chronic social defeat stress. Activity patterns in this network originate in prefrontal cortex and ventral striatum, relay through amygdala and ventral tegmental area, and converge in ventral hippocampus. This network is increased by acute threat, and it is also enhanced in three independent models of MDD vulnerability. Finally, we demonstrate that this vulnerability network is biologically distinct from the networks that encode dysfunction after stress. Thus, these findings reveal a convergent mechanism through which MDD vulnerability is mediated in the brain.
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A spatiotemporal dynamic network originating in PFC and ventral striatum, relaying through amygdala and VTA, and converging in vHIP encodes depression vulnerability in mice subjected to social defeat stress.
“A spatiotemporal dynamic network, which originates in PFC and ventral striatum, relays through the amygdala and ventral tegmental area (VTA), and converges in ventral hippocampus (vHIP), is found to encode depression vulnerability in mice subjected to social defeat stress 20.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [20]
Alterations in VTA DA activity affect activity in multiple downstream targets, including the NAc and mPFC, which appear to be particularly important for mediating social avoidance.
“Alterations in VTA DA activity will affect activity in multiple downstream targets, including the NAc and mPFC, which appear to be particularly important for mediating social avoidance [149, 150, 156-159].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [157]
Brain-wide electrophysiological monitoring in mice revealed a stress vulnerability network that included mPFC, amygdala, NAc, vHip and VTA.
“In mice, this method revealed a stress vulnerability network that included many of the brain regions mentioned thus far including mPFC, amygdala, NAc, vHip and VTA [157].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [157]
The stress vulnerability network was distinct from the network activity underlying the expression of aberrant behaviors elicited by CSDS.
“this vulnerability network was distinct from the network activity underlying the expression of aberrant behaviors elicited by CSDS [157].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [157]
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- Authors
- Hultman, R., Ulrich, K., Sachs, B. D., Blount, C., Carlson, D. E., Ndubuizu, N., Bagot, R. C., Parise, E. M., Vu, M.-A. T., Gallagher, N. M., Wang, J., Silva, A. J., Deisseroth, K., Mague, S. D., Caron, M. G., Nestler, E. J., Carin, L., & Dzirasa, K.
- Affiliations
- Duke Medical Center (US)
- Duke University (US)
- Villanova University (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of California, Los Angeles (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Carin, Lawrence
- Dzirasa, Kafui
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 173
- Issue
- 1
- Pages
- 166-180.e14
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6005365
- OpenAlex
- W2794251999
- Cited by
- 183
- References
- 52
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 21 · 2023: 19 · 2022: 39 · 2021: 23 · 2020: 23 · 2019: 19 · 2018: 1
- FWCI
- 9.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (MH79201-03S1, MH79201, MH099192-05S1, MH099192-05S2, MH096890, MH099192)
- Lennon Family Foundation
- DARPA HIST Program
- One Mind Institute
- Kerima L. Collier
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- major depressive disorder, depression vulnerability, local field potentials, spatiotemporal dynamics, chronic social defeat stress, prefrontal cortex, ventral striatum, amygdala, ventral tegmental area, ventral hippocampus, threat response, mouse model
- MeSH terms
- Machine Learning, Animals, Brain, Depression, Disease Models, Animal, Electric Stimulation, Electrodes, Implanted, Immunoglobulin G, Ketamine, Male, Membrane Proteins, Mice, Inbred C57BL, Physiological Phenomena, Stress, Psychological, Prefrontal Cortex, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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