Assessing the functional role of adult hippocampal neurogenesis in humans using cognitive and neurobiological correlates

Abstract

Adult hippocampal neurogenesis, the generation of new neurons in the adult hippocampus, represents the most drastic form of ongoing plasticity in the human brain. When these adult-born neurons are a few weeks old, they have developed enough connections with surrounding hippocampal neurons to evoke meaningful change in network dynamics, but still have different morphological and physiological properties compared to developmentally generated neurons that render them more plastic. As such, and due to their location in the hippocampus, many have theorized that these new neurons play an important role in certain forms of learning memory as well as emotion. This dissertation outlines the first attempt to answer the question “what are new neurons in the hippocampus good for?” using human participants. Aerobic exercise is a lifestyle factor well-established from the animal literature to upregulate neurogenesis, while chronic stress is a known downregulator of neurogenesis. The second chapter of this thesis describes a study in which aerobic capacity and depression inventory scores demonstrated a significant positive correlation and a significant negative correlation with putative neurogenesis-dependent memory, respectively, in separate cohorts of healthy young adults. The third chapter outlines a study that expands on the one presented in the second by elucidating another potential role for neurogenesis in human cognition – remote memory. Finally, Chapter 4 describes a study investigating the utility of neurotrophins measured from peripheral blood as biomarkers for neurogenic activity in humans by examining how changes in their expression following chronic exercise predict changes in putative neurogenesis-dependent memory performance. These studies are the first to explicitly test and provide supporting evidence for the theoretical roles of adult hippocampal neurogenesis in humans. Taken together, these studies provide a strong foundation for how investigators and clinicians can indirectly quantify and test the function of adult-born neurons in the human brain.