Gene-environment interactions in the regulation of cellular plasticity, cognitive function and behaviour
The hippocampus is a dynamic brain structure believed to be critical to cognitive functions including memory consolidation and emotion regulation. One of its unusual features is that the dentate gyrus subfield is known to engage in the process of neurogenesis throughout adulthood, constitutively. Interestingly, this process is not static, and behavioural manipulations, such as housing animals in an enriched environment (EE) or allowing them to engage in voluntary exercise (VEx) on a running wheel, can increase the rate of hippocampal neurogenesis.
The real impact of enhanced hippocampal neuroplasticity on cognitive functions remains unclear, and very few studies have used genetically targeted animals to unravel neuroplasticity mechanisms associated with the effects of long-term environmental manipulations.
Serotonin (5-HT) is known to influence adult neurogenesis. Recent studies suggest that 5-HT in the hippocampus is more instrumental in cell proliferation than cell survival; this might account for the differences in proliferation and survival observed between VEx and EE. In addition, existing research suggests a sex difference in the regulation of hippocampal neurogenesis and sexually dimorphic neurochemical changes underlying the effects of environmental factors on hippocampal-related functions such as memory and emotion regulation.
Further studies are necessary to substantiate sex differences in gene-environment interactions on hippocampal-related functions. The role of 5-HT in the cellular changes induced by both EE and VEx needs to be explored more exhaustively to elucidate its involvement in the process of neurogenesis. Surprisingly, although they display valuable advantages, no study has yet used genetically targeted animal models with disrupted 5-HT signalling for such fundamental explorations. These questions will be the focus of this project.