The influence of stress on the connectivity of developmentally-born and adult-born neurons within the hippocampal dentate gyrus-CA3 pathway

The discovery that humans are able to regenerate new neurons through a process called neurogenesis has transformed our understanding of the brain’s potential for plasticity. In the dentate gyrus (DG) subregion of the hippocampus, adult neurogenesis plays an important role both in memory and emotional processes such as depression. The neural pathway, DG-CA3 in this region shows remarkable learning-induced plasticity and is an important component of the brain’s stress-regulation circuitry. Though the mechanisms by which new neurons regulate stress and depression-related behaviour are largely unclear, they are likely to be critically dependent on their connections with downstream dorsal vs. ventral hippocampal subregions, which are involved in cognitive vs. emotional behaviours. Since the adult-born and pre-existing neuronal populations are each very large, understanding the role of the DG-CA3 pathway in stress-regulation and depression will require dissection of the circuits created during development vs. those created during adulthood.

This study will examine the influence of stress on the connectivity and plasticity of adult-born neurons in a rat model.

First, Dr. O’Leary will use a microscopal imaging technique to determine whether patterns of connectivity differ between pre-existing and adult-born neurons. Second, Dr. O’Leary will determine how stress in adult-hood modifies the pattern of connectivity in pre-existing and adult-born neurons. Following either acute or chronic restraint stress in adult-hood, anxiety-like behaviour, depressive-like behaviour, and patterns of neuronal connectivity will be measured.

Dr. O’Leary hypothesizes that stress will influence the pattern of connectivity of adult-born neurons within the ventral hippocampus, and these changes will correlate with anxiety- and depressive-like behaviours. This research will elucidate a novel mechanism by which stress contributes to depression in humans.