An Investigation of the Effect of Chronic Unpredictable Stress on Hippocampal Integrity and Spatial Learning
Chronic stress has been shown to induce neuroplastic changes in the hippocampus, decrease the survival of progenitor cells in the hippocampus, and impair hippocampal-dependent learning and memory. Recent evidence suggests that the hippocampus has two functionally distinct subregions. The dorsal portion appears to be primarily associated with spatial navigation, while the ventral region has been linked to anxiety-related functions. Regionally-specific neuroplastic changes in the dorsal and ventral subregions of the hippocampus suggest that the hippocampus may play a dual role in the stress response. We previously demonstrated that following chronic unpredictable stress (CUS), markers of neuroplasticity were preserved specifically in the dorsal dentate gyrus (DG) of the hippocampus. Considering that hippocampal integrity is imperative for learning and memory, we hypothesized that the increased markers of neuroplasticity observed in the dorsal DG of CUS-exposed animals would enhance performance on tests of spatial navigation ability. In the present investigation, spatial navigation on the radial arm water maze (RAWM) was assessed in rats following exposure to CUS, as well as neurogenesis, neuroprotective proteins, and synaptic plasticity in the dorsal and ventral DG of the hippocampus. Despite similarly elevated levels of corticosterone, stressed animals found the hidden platform faster and with fewer errors on the RAWM long-term memory trial compared to control animals. Furthermore, elevated coriticosterone in control and stressed animals exposed to the RAWM had decreased cell proliferation (CldU) and neurogenesis (DCX) in the ventral DG. Stressed animals also had decreased cell survival (IdU) in the ventral DG. Proteins proBDNF and PSD-95, which promote LTP and synaptic plasticity, were increased in the dorsal DG. Stressed animals had increased neuroprotective proteins and preserved neuroplasticity in the dorsal DG, which may have contributed to the improved spatial navigation abilities on the RAWM. These regionally-specific neuroplastic changes suggest that the hippocampus does, in fact, play a dual role in response to chronic stress, and chronic stress does not impair spatial learning and memory.