Unbiased stereological counting methods showed that total number estimation of c-Fos (+) nuclei, indicating the neuronal activation upon stressful challenge, significantly increased in high anxious animals compared with low anxious and control groups, in both gender. Golgi–Cox staining of neurons displayed anxiety level- and sex-dependent reduction in the dendritic complexity and spine density of pyramidal neurons, especially in the stressed males. While the total length of dendrites were not correlational; density of spines, specifically the mushroom subtypes, showed a negative correlation with the anxiety level of stressed animals.
These results suggest that medial PFC is a critical site of neural plasticity within the stressor controllability paradigm. Outcomes of early life stress might be predicted by analyzing the density and morphology of spines in the apical dendrites of pyramidal neurons in correlation with the anxiety-like behavior of animals.