IκB kinase regulates social defeat stress-induced synaptic and behavioral plasticity

Daniel J. Christoffel, Sam A. Golden, Dani Dumitriu, Alfred J. Robison, William G. Janssen, H. Francisca Ahn, Vaishnav Krishnan, Cindy M. Reyes, Ming Hu Han, Jessica L. Ables, Amelia J. Eisch, David M. Dietz, Deveroux Ferguson, Rachael L. Neve, Paul Greengard, Yong Kim, John H. Morrison, Scott J. Russo

Research output: Contribution to journalArticle

184 Scopus citations

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 Luciferyellow-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.

Original languageEnglish (US)
Pages (from-to)314-321
Number of pages8
JournalJournal of Neuroscience
Volume31
Issue number1
DOIs
StatePublished - Jan 5 2011

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'IκB kinase regulates social defeat stress-induced synaptic and behavioral plasticity'. Together they form a unique fingerprint.

  • Cite this

    Christoffel, D. J., Golden, S. A., Dumitriu, D., Robison, A. J., Janssen, W. G., Ahn, H. F., Krishnan, V., Reyes, C. M., Han, M. H., Ables, J. L., Eisch, A. J., Dietz, D. M., Ferguson, D., Neve, R. L., Greengard, P., Kim, Y., Morrison, J. H., & Russo, S. J. (2011). IκB kinase regulates social defeat stress-induced synaptic and behavioral plasticity. Journal of Neuroscience, 31(1), 314-321. https://doi.org/10.1523/JNEUROSCI.4763-10.2011