I kappa B Kinase Regulates Social Defeat Stress-Induced Synaptic and Behavioral Plasticity
Name
Christoffel-2011-I kappa B Kinase Regulates Social Defeat Stress-Induced Synaptic and Behavioral Plasticity.pdf
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1.55 MB
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Checksum (MD5)
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Author(s)
Christoffel, Daniel J.
Golden, Sam A.
Dumitriu, Dani
Robison, Alfred J.
Janssen, William G.
Ahn, H. Francisca
Krishnan, Vaishnav
Reyes, Cindy M.
Han, Ming-Hu
Ables, Jessica L.
Alternative Title
IkB Kinase Regulates Social Defeat Stress-Induced Synaptic and Behavioral Plasticity
Date Issued
January 2011
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Christoffel, Daniel J. et al. “I kappa B Kinase Regulates Social Defeat Stress-Induced Synaptic and Behavioral Plasticity.” The Journal of Neuroscience 31.1 (2011) : 314 -321.
Version
Final published version
Abstract
The neurobiological underpinnings of mood and anxiety disorders have been linked to the nucleus accumbens (NAc), a region important in processing the rewarding and emotional salience of stimuli. Using chronic social defeat stress, an animal model of mood and anxiety disorders, we investigated whether alterations in synaptic plasticity are responsible for the long-lasting behavioral symptoms induced by this form of stress. We hypothesized that chronic social defeat stress alters synaptic strength or connectivity of medium spiny neurons (MSNs) in the NAc to induce social avoidance. To test this, we analyzed the synaptic profile of MSNs via confocal imaging of Lucifer-yellow-filled cells, ultrastructural analysis of the postsynaptic density, and electrophysiological recordings of miniature EPSCs (mEPSCs) in mice after social defeat. We found that NAc MSNs have more stubby spine structures with smaller postsynaptic densities and an increase in the frequency of mEPSCs after social defeat. In parallel to these structural changes, we observed significant increases in IκB kinase (IKK) in the NAc after social defeat, a molecular pathway that has been shown to regulate neuronal morphology. Indeed, we find using viral-mediated gene transfer of dominant-negative and constitutively active IKK mutants that activation of IKK signaling pathways during social defeat is both necessary and sufficient to induce synaptic alterations and behavioral effects of the stress. These studies establish a causal role for IKK in regulating stress-induced adaptive plasticity and may present a novel target for drug development in the treatment of mood and anxiety disorders in humans.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
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DOI of Published Version
https://doi.org/10.1523/jneurosci.4763-10.2011
