Hippocampus research introduces a new understanding of stress

In Aug. 2019, a team led by McGill professor and researcher Tak Pan Wong published a new study about the hippocampus and its ability to retain memories of stressful experiences. Published in the Journal for Neuroscience, the study detailed new connections to mental disorders such as depression and post-traumatic stress disorder. By exposing mice to social stress in the form of physical threats from other mice, Wong and his team found that negative memory traces were left on the hippocampus, the part of the brain primarily responsible for memory and spatial recognition.

In an interview with The McGill Tribune, Wong explained that the inspiration for the study was the growing interest in understanding the biological mechanisms underlying sensitivity to stress. Researchers originally predicted that increased sensitivity to stressknown to negatively impact learning and memory—was related to reduced hippocampal function.

“Surprisingly, using MRIs [magnetic resonance imaging] to compare [the] hippocampal volume[s] of mice that [were] either susceptible or resilient to stress revealed a bigger hippocampus in susceptible mice,” Wong said.

The hippocampus is a part of the brain located under the cerebral cortex in the medial temporal lobe. It plays a central role in long-term memory formation and spatial recognition, though the study focused only on the former. The hippocampus is thought to record memories of negative events, which leads to the activation of a group of neurons called engrams. The study found that mice that are genetically more sensitive to stressful environments experienced the overactivation of certain engrams in the hippocampus and were more likely to exhibit depressive and aversive behaviours, namely social avoidance.  

Wong explained that, though spatial orientation and recognition of the outside environment were likely not directly affected by exposure to social stress, the entire hippocampal region was put under distress. A 2018 paper showed that when put in a stressful situation, the neurons in the hippocampus responsible for getting an accurate image of one’s outside environment register poorly, influencing the long-term memory and reactivation when placed back in the same situation. The group of neurons for this place field are thus a lot less responsive when activated by stressful experiences. 

“These findings suggest the presence of distinct populations of neurons for accurate encoding of spatial information and fear memory,” Wong said.

New knowledge on the effect of traumatic memories on the hippocampus can offer new insights on the role that memory plays in people with depressive disorders. Depression is known to have cognitive symptoms such as difficulty concentrating, forgetfulness, and memory loss. In the study, repeated exposure to social stress in some mice led to overactivation in certain parts of the hippocampus, causing depressive behaviours like social avoidance. This is also a common symptom for those with depression or post-traumatic stress, as there is a fear of being judged or criticised. In his research, Wong found that activating engrams led to increased avoidance behaviours, while deactivating engrams reduced these behaviours, thus demonstrating a relationship between an overactive engram and depressive symptoms. 

Moving forward, Wong is interested in exploring whether functional changes to place cells may somehow also be related to stress sensitivity. 

Though the study demonstrated the results of stress exposure in mice, the mental and social abilities of humans are more complex. People experience, respond, and manifest stress in different and more subtle ways. Nonetheless, the study opens a new path for depression research and is a cornerstone to future studies regarding memory formation and depressive disorders.

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