Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex

Radley, J.J. et al. (2005). Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cerebral Cortex, 16, 313-320.

The medial prefrontal cortex (mPFC) plays an important role in higher cognitive processes and in the regulation of stress-induced HPA axis activity. This study investigated the effect of stress on dendritic spine density in the mPFC. Rats were restrained for 6 hours daily for 21 days with wire mesh. Following the 21 days of stress, stressed rats weighed less than controls, had a 20% decrease in overall apical dendritic length, a 16% decrease in apical dendritic spine density, and hence an estimated 33% reduction in the total number of axospinous synapses on apical dendrites of pyramidal neurons in the mPFC. These morphological changes may have a significant impact on the functional properties of this region. Clinically, mPFC dysfunction is associated with PTSD and depression. One potential neuroanatomical substrate relevant to these disorders is the mPFC-amygdala circuit. Normally, the mPFC may inhibit amygdala output through its connections on the GABAergic intercalated cells at the border of the lateral and central nuclei of the amygdala. Experimental lesions of the mPFC support this, leading to an enhancement of amygdala-dependent behaviors such as emotionality and fear conditioning. Future studies are needed to investigate the extent to which these morphological changes from chronic stress are reversible.