Stress-induced dendritic remodeling in the medial prefrontal cortex: effects of circuit, hormones and rest

Abstract

The medial prefrontal cortex (mPFC) has been implicated as a site of dysfunction and abnormal morphology in major depressive disorder and post-traumatic stress disorder, two illnesses that can be brought on by exposure to stress. In animal models, stress has long been shown to induce impairments in tasks known to be mediated by the mPFC, and recent work has demonstrated that chronic stress can lead to morphological changes in mPFC pyramidal cells. This review explores the current literature on stress-induced dendritic remodeling in the mPFC, with particular focus on new findings that illuminate modulators of these effects.

Figure 1. Chronic restraint stress causes dendritic remodeling in mPFC dendrites and spines

(a) a layer II/III pyramidal mPFC neuron filled with Lucifer Yellow to allow for dendrite visualization. (b) and (c) dendrite segments from control and stress groups, demonstrating spine loss. (d) NeuronStudio software reconstruction of a dendritic segment, demonstrating spine size measurements. (e) and (f) 21 days restraint stress causes significant decrease in total apical dendrite length and in spine density. (g) Chronic restraint stress also causes a shift in spine size, with dendrites exhibiting a smaller percentage of large spines. Adapted from (Radley et al., 2004), (Radley et al., 2006) and (Radley et al., 2008). * p < 0.05

Figure 2. The effects of chronic stress in the mPFC are circuit- and estrogen-dependent

(a) A Lucifer Yellow-filled mPFC pyramidal cell surrounded by FastBlue-labeled cells, demonstrating the technique for selectively loading BLA-projecting neurons. Representative Neurolucida tracings of BLA-projecting neurons from OVX + E control (b) and stress (c) groups. In randomly-selected neurons (d), males, but not females, displayed stress-induced dendritic retraction. However, in BLA-projecting neurons (e), males and OVX + veh showed no stress-induced changes, while OVX + E exhibited stress-induced dendritic expansion. Stress-induced increases in spine density (f) were seen in BLA-projecting neurons of both OVX + veh and OVX + E but not males, and estrogen alone increased spine density in control animals. * p < 0.05 compared to same-group control; *** p < 0.0001 compared to same-group control; † p < 0.05 compared to OVX + veh control. Adapted from (Shansky et al., 2009) and Shansky et al, unpublished observations.