Region‐specific response of the hippocampus to chronic unpredictable stress

Abstract

The objective of the present study was to determine whether chronic unpredictable stress (CUS) would induce hippocampal neuroplasticity in a region-specific manner. Recent evidence suggests that the hippocampus has two functionally distinct subsections. The dorsal (septal) portion appears to be primarily associated with spatial navigation, while the ventral (temporal) region has been linked to affect-related functions, such as anxiety. Chronic stress has previously been shown to negatively affect the hippocampus by decreasing survival of progenitor cells, although it has also been shown to increase adaptive responses, such as increased expression of neuropeptide Y (NPY) and ΔFosB. Whether such events occur in a region-specific manner has not been investigated. We hypothesized that CUS would selectively impact cell survival, NPY, and ΔFosB expression in the more affect-related ventral subregion. Individually housed Long-Evans rats (n = 31) were divided into two groups: stressed and control. Stressed animals were exposed daily to an unpredictable schedule of ethologically relevant stressors, such as predator odors, forced swim, and open field exposure. All rats were injected with bromodeoxyuridine (BrdU) daily during the first 5 days of CUS in order to label dividing progenitor cells. Unbiased stereology was used to quantify BrdU+, NPY+, and ΔFosB+ cells in dorsal and ventral hippocampal subregions. In support of our hypothesis, we found that CUS selectively decreased cell survival in the ventral subregion. However, both NPY and ΔFosB were significantly increased only in the dorsal hippocampus. These results suggest that stress-induced adaptive neuroplasticity occurs primarily in the dorsal subregion, which may coincide with behavioral aspects of the stress response, such as avoidance or amelioration of the stressor.