Time course of neuronal effects as a result of post‐traumatic stress disorder (PTSD)‐relevant social stress on a mouse model

Abstract

Impaired fear extinction, associated with decreased activation in the ventromedial prefrontal cortex (mPFC), has been reported in subjects with PTSD. In rodents, chronic exposure to stressors induced atrophy in mPFC, associated with disruption of working memory and behavioral flexibility. There is a need to identify neurobiological markers for mPFC dysfunction associated with PTSD. The social stress (SS) model in C57/BL6 mice reliably elicits PTSD‐like behaviors. SS or control (C) mice were housed in a small box (without food or liquid) within a larger cage for 6 h/d for 10 d. SS, but not C mice, were exposed to an aggressor mouse at random intervals (3x/d). Analysis of mPFC in golgi‐impregnated brains showed different responses to SS in multipolar (MP) vs. pyramidal (PRM) cells. 24 h after 10d in SS, MP cells in SS mice had lower dendritic spine density (DSD) and length (SL) with a larger percent stubby spines vs. C, yet were similar to C at 4 wks after 10 d SS. In contrast, PRM cells in SS mice showed no differences from C at 24 h post‐SS. At 4 wks post‐SS, however, DSD and SL increased in C but remained at 24 h in SS, thus, were lower than C at 4wks. Morphologically, at 4wks, the percent mushroom increased and percent stubby decreased in C but not in SS, leaving SS with a higher percent stubby than C. The effect of SS on PRM cells appears to be more persistent over time, suggesting a cell‐specific temporal modulation.