Synaptic modifications in the medial prefrontal cortex in susceptibility and resilience to stress

Wang, M., Perova, Z., Arenkiel, B. R., Li, B. (May 2014) Synaptic modifications in the medial prefrontal cortex in susceptibility and resilience to stress. Journal of Neuroscience, 34 (22). pp. 7485-92. ISSN 0270-6474

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DOI: 10.1523/JNEUROSCI.5294-13.201


When facing stress, most individuals are resilient whereas others are prone to developing mood disorders. The brain mechanisms underlying such divergent behavioral responses remain unclear. Here we used the learned helplessness procedure in mice to examine the role of the medial prefrontal cortex (mPFC), a brain region highly implicated in both clinical and animal models of depression, in adaptive and maladaptive behavioral responses to stress. We found that uncontrollable and inescapable stress induced behavioral state-dependent changes in the excitatory synapses onto a subset of mPFC neurons: those that were activated during behavioral responses as indicated by their expression of the activity reporter c-Fos. Whereas synaptic potentiation was linked to learned helplessness, a depression-like behavior, synaptic weakening, was associated with resilience to stress. Notably, enhancing the activity of mPFC neurons using a chemical-genetic method was sufficient to convert the resilient behavior into helplessness. Our results provide direct evidence that mPFC dysfunction is linked to maladaptive behavioral responses to stress, and suggest that enhanced excitatory synaptic drive onto mPFC neurons may underlie the previously reported hyperactivity of this brain region in depression.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > tissues types and functions > prefrontal cortex
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > synaptic plasticity
CSHL Authors:
Communities: CSHL labs > Li lab
School of Biological Sciences > Publications
Stanley Institute for Cognitive Genomics
Depositing User: Matt Covey
Date: 28 May 2014
Date Deposited: 09 Jun 2014 19:18
Last Modified: 06 Nov 2015 20:49
PMCID: PMC4035514
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