Increasing Adult Hippocampal Neurogenesis affects Neuronal Output Pattern from the Ventral Subiculum to the Hypothalamus

Abstract

Adult Hippocampal Neurogenesis, or AHN, has been discovered to alleviate anxiety and depressive behavior, thus leading to the presumption that the mechanisms underlying it might be somewhat linked to the regulatory circuitry of anxiety and depression. The subiculum is a region of the Hippocampus connecting the CA1 neurons and the Entorhinal cortex. It is the main output region of the Hippocampus. A great portion of the subiculum neurons form neuronal projections to the lateral hypothalamus, which is known to play a crucial role in the regulation of anxiety via hormone secretion in both rodents and humans. Thus, we hypothesize that Adult Hippocampal Neurogenesis regulates anxiety via altering the neural output from the subiculum to the lateral hypothalamus. In this research proposal we aim to prove that increasing AHN causes a direct impact on neuronal activity in the main output region of the Hippocampus--the subiculum region, under the effect of anxiety. This study uses the Fos-TRAP2 model to induce tdTomato expression in neurons with high recent activity while the mice was under the effect of corticosterone-induced anxiety. We compare the amount of TRAPed neurons in the subiculum region of the brain during anxiety, in mice with and without weeks of voluntary exercise (running), which leads to an increased neurogenesis. This provides insight into the effects of AHN on the subiculum-hypothalamus pathway, thus the mechanisms underlying its effect of anxiety alleviation.