Chronic Stress-induced Behaviors Correlate with Exacerbated Acute Stress-induced Cingulate Cortex and Ventral Hippocampus Activation

Neuroscience, August 2020

Authors: Corey Fee, Thomas Prevot, Keith Misquitta, Mounira Banasr, and Etienne Sibille

Sibille Lab PhD Student, Corey Fee, published the findings of his research in the August edition of Neuroscience (Volume 440, 1 August 2020, Pages 113-129), where he identified a functional change in the brain’s response to acute stress that supports the emergence of behaviors related to depression and other chronic stress-related illnesses.

Paper Highlights
• Chronic stress models produce variable profiles of physiological deficits, anxiety-like behavior, and impaired memory.
• Acute stress-induced activation of ACC A24b & vHPC is exacerbated by prior chronic stress exposure.
• In regions dysregulated by chronic stress, altered neuronal activation is positively correlated with behavioral deficits.

Paper Abstract
Altered activity of corticolimbic brain regions is a hallmark of stress-related illnesses, including mood disorders, neurodegenerative diseases, and substance abuse disorders. Acute stress adaptively recruits brain region-specific functions for coping, while sustained activation under chronic stress may overwhelm feedback mechanisms and lead to pathological cellular and behavioral responses. The neural mechanisms underlying dysregulated stress responses and how they contribute to behavioral deficits are poorly characterized. Here, we tested whether prior exposure to chronic restraint stress (CRS) or unpredictable chronic mild stress (UCMS) in mice could alter functional response to acute stress and whether these changes are associated with chronic stress-induced behavioral deficits. More specifically, we assessed acute stress-induced functional activation indexed by c-Fos+ cell counts in 24 stress- and mood-related brain regions, and determined if changes in functional activation were linked to chronic stress-induced behavioral impairments, summarized across dimensions through principal component analysis (PCA). Results indicated that CRS and UCMS led to convergent physiological and anxiety-like deficits, whereas working and short-term memory were impaired only in UCMS mice. CRS and UCMS exposure exacerbated functional activation by acute stress in anterior cingulate cortex (ACC) area 24b and ventral hippocampal (vHPC) CA1, CA3, and subiculum. In dysregulated brain regions, levels of functional activation were positively correlated with principal components reflecting variance across behavioral deficits relevant to stress-related disorders. Our data supports an association between a dysregulated stress response, altered functional corticolimbic excitation/inhibition balance, and the expression of maladaptive behaviors.