IκB Kinase Regulates Social Defeat Stress-Induced Synaptic and Behavioral Plasticity
Open Access
- 5 January 2011
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 31 (1), 314-321
- https://doi.org/10.1523/jneurosci.4763-10.2011
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.Keywords
This publication has 61 references indexed in Scilit:
- ΔFosB in brain reward circuits mediates resilience to stress and antidepressant responsesNature Neuroscience, 2010
- Nuclear factor-κB is a critical mediator of stress-impaired neurogenesis and depressive behaviorProceedings of the National Academy of Sciences of the United States of America, 2010
- Axospinous synaptic subtype‐specific differences in structure, size, ionotropic receptor expression, and connectivity in apical dendritic regions of rat hippocampal CA1 pyramidal neuronsJournal of Comparative Neurology, 2008
- The structural basis for mapping behavior onto the ventral striatum and its subdivisionsBrain Structure and Function, 2008
- Intense cocaine self-administration after episodic social defeat stress, but not after aggressive behavior: dissociation from corticosterone activationPsychopharmacology, 2005
- Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey ReplicationArchives of General Psychiatry, 2005
- Synaptogenesis on mature hippocampal dendrites occurs via filopodia and immature spines during blocked synaptic transmissionJournal of Comparative Neurology, 2005
- CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuliProceedings of the National Academy of Sciences of the United States of America, 2002
- Molecular basis of long-term plasticity underlying addictionNature Reviews Neuroscience, 2001
- Mechanisms of Calcium Decay Kinetics in Hippocampal Spines: Role of Spine Calcium Pumps and Calcium Diffusion through the Spine Neck in Biochemical CompartmentalizationJournal of Neuroscience, 2000