Stress and hippocampal volume in rodents, a longitudinal study

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The impact of stress on memory is at least partly due to its influences on the hippocampus, a brain region that is important for learning and memory. Although chronic stress could reduce hippocampal volume, the functional significance of hippocampal shrinkage remains unclear. The difficulty of understanding the functional significance of hippocampal shrinkage may be partly caused by the almost exclusive use of a cross-sectional approach to investigate hippocampal volume differences between stressed and non-stressed individuals. Cross-sectional studies however fail to reveal causality. Another problem is related to the failure to control for individual differences in stress susceptibility in most stress studies. Investigating psychopathologies in people that had experienced wide scale traumatic events revealed that not all people are similarly affected by these events, so that some individual were resilient to trauma. ******This new NSERC application is built on an emerging long term objective of my laboratory to reveal the functional significances and mechanisms of stress-induced hippocampal shrinkage. Using a non-invasive MRI approach to measure hippocampal volume before and after stress exposure, we have found that mice that are susceptible to chronic social defeat stress displayed stress-induced volume changes. Nonetheless, these changes were not found in mice that are resilient to chronic social defeat. Our short term objective is to use this social defeat model that allows us to separate mice that are susceptible or resilient to chronic stress to test the following hypotheses: 1) resilient mice exhibit a resistance to stress-induced hippocampal shrinkage; 2) chronic stress exerts opposing effects on the volume of the dorsal and ventral hippocampus, which are responsible for spatial and emotional memory formation, respectively, and 3) stress-induced hippocampal shrinkage is related to dendritic reorganization and microglia proliferation.******Findings from this research program could not only advance our understanding of the functional significance and mechanisms of stress-induced hippocampal shrinkage, but also allow us to develop a new research avenue for longitudinally investigating changes in mouse brain structures. This research program complements the ongoing research of my lab to investigate the impact of stress on hippocampal synaptic function. Training from this research program could equip trainees to use non-invasive imaging approaches on mice, which are powerful but newly emerging research techniques that could help them develop their career in both academia and industry.