Are you stressed? Over millions of people worldwide are affected by major depressive disorder. Out of those who receive current antidepressant treatments, over 50% of patients relapse and almost a third are drug resistant. Over the years, many treatments have been refined, but without much efficacy. The inner workings of the treatments still aren’t well understood primarily because we don’t have an in depth profile for depression. In order to be able to create more reliable treatments for depression, we must further investigate its effects on the brain so that we can accurately target regions that will provide promising results. 

Major depressive disorder is marked by hippocampal dysfunction and current chronic antidepressants reduce that dysfunction. However, targeting certain regions in the hippocampus doesn’t have positive effects on mood regulation. Therefore, we look to target cortical brain regions like the entorhinal cortex, since it is easily accessible and more preferable than targeting a deeper brain region. 

Previously, we focused on the excitatory entorhinal cortex's antidepressant-like efficacy, but the function of inhibitory neurons in the entorhinal cortex has not yet been studied. Here, we studied the response of  inhibitory local EC neurons and long-range inhibitory projections to chronic stress. We tracked the brain activity of the entorhinal cortex interneurons and the entorhinal cortex long-range inhibitory projections, during the behavior tests. The results from this study will give us a better idea of the role the entorhinal cortex plays in major depressive disorder as well as a look into the resilience and susceptibility after chronic stress. We hope that our findings contribute to the creation of more accurate treatments for depression so that we can better the lives of many worldwide.