What is the functional significance of chronic stress-induced CA3 dendritic retraction within the hippocampus?

Chronic stress produces consistent and reversible changes within the dendritic arbors of CA3 hippocampal neurons, characterized by decreased dendritic length and reduced branch number. This chronic stress-induced dendritic retraction has traditionally corresponded to hippocampus-dependent spatial memory deficits. However, anomalous findings have raised doubts as to whether a CA3 dendritic retraction is sufficient to compromise hippocampal function. The purpose of this review is to outline the mechanism underlying chronic stress-induced CA3 dendritic retraction and to explain why CA3 dendritic retraction has been thought to mediate spatial memory. The anomalous findings provide support for a modified hypothesis, in which chronic stress is proposed to induce CA3 dendritic retraction, which then disrupts hypothalamic-pituitary-adrenal axis activity, leading to dysregulated glucocorticoid release. The combination of hippocampal CA3 dendritic retraction and elevated glucocorticoid release contributes to impaired spatial memory. These findings are presented in the context of clinical conditions associated with elevated glucocorticoids.