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Hultman, Rainbo; Ulrich, Kyle; Sachs, Benjamin D.; Blount, Cameron; Carlson, David E.; Ndubuizu, Nkemdilim; Bagot, Rosemary C.; Parise, Eric M.; Vu, Mai-Anh T.; Gallagher, Neil M.; Wang, Joyce; Silva, Alcino J.; Deisseroth, Karl; Mague, Stephen D.; Caron, Marc G.; Nestler, Eric J.; Carin, Lawrence; Dzirasa, Kafui
Cell, 03/2018, Volume: 173, Issue: 1Journal Article
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. Display omitted •Brain-wide electrical spatiotemporal dynamic map of stress states•Hippocampally directed network signals stress vulnerability in stress-naive animals•Early life stress increases activity in stress vulnerability network•Stress vulnerability network is mechanistically distinct from pathology networks Patterns of brain activity predict vulnerability versus resilience to depression in response to stress.
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