Open Collections

Regulation of developmentally-born and adult-born neurons in the dentate gyrus

University of British Columbia

The discovery that neurons are added to the adult brain of nearly all mammals examined, including humans, has had profound effects on our understanding of the potential for plasticity in the brain. There has been an overwhelming focus on understanding the unique properties of adult-born neurons, often at the expense of another important cell population: the already present developmentally-born neurons. While the stages and integration of neurons in adulthood have been relatively well characterized, less is known about how developmentally-born cells integrate and survive over time and are regulated by experience. Since the dentate gyrus (DG) is comprised of large numbers of both populations, identifying the properties of these two populations and their relationship is essential for understanding how the dentate gyrus contributes to memory and behaviour. In chapter 2 we show that developmentally-born neurons die in early adulthood, unlike adult-born cells, which are known to remain stable (after reaching maturity). While adult-born neurons are unique during their immature stages, many reports indicate that they may become functionally equivalent to neurons born in early postnatal development once they have reached maturity. These data collectively suggest that adult neurogenesis may serve to replace lost developmentally-born cells. In chapter 3 we show that alternating 4-week blocks of running and memantine, an NMDA antagonist, produces sustained increases in adult neurogenesis in males, while in females interval running increased adult neurogenesis. In chapter 4 the relationship between the two populations was investigated using either neurogenesis-promoting or suppressing treatments during early adulthood. We found that that increasing adult neurogenesis decreases the activity in the DG and specifically in developmentally born neurons, indicating that there is a functional relationship between the two populations, and that adult-born neurons may act to inhibit older neurons. This thesis set out to better describe both the developmentally-born and adult-born neuronal populations and investigate the relationships between these two populations. Collectively, these data hope to clarify whether there are interactions between neurons born throughout the lifespan, which may shape how information is retained in the hippocampus and could prioritize treatments that are aimed at generating new cells vs. preserving older cells.

Text

2019-03-13

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/68684

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/