By Snigdha Kanadibhotla ‘21

Conventionally, humans were thought to be born with a fixed number of nerve cells or neurons that steadily deteriorated over their lifetime; as a result, degenerative brain diseases were thought to be untreatable. However, studies involving animal models have challenged this idea by demonstrating that during adulthood, neurogenesis or the creation of new neurons can occur in the hippocampus which isa brain region important for learning and memory.

Early studies involving songbirds discovered that the rate of hippocampal neurogenesis in adult songbirds varied with season, and that songbirds raised in more stimulating environments developed new neurons as adults. This prompted questions about whether adult neurogenesis was the result of neuroplasticity – the ability of the brain to alter synaptic connections in response to experiences – or the result of a predetermined genetic plan. Neurogenesis is two-fold: (1) neuronal development (the generation of new neurons) and (2) neuronal survival (the survival of neurons after development).

In order to determine the role of neuroplasticity in neurogenesis, a study was conducted that exposed two groups of rat animal models to two different learning environments, one group for a short period of time and the other group for a longer period. The duration of the experiences was designed to independently manipulate neuronal development and neuronal survival, respectively, under the reasoning that a new experience is required to develop neurons, but consistent stimulation is required to keep them alive. Shortly before being placed in the learning environment, rats in both groups were injected with the nucleoside (a monomer of DNA) and genetic marker 5-bromo-2′-deoxyuridine (BrdU). When BrdU is injected into the hippocampus, it is integrated into the DNA of a replicating neuronal cell. A fluorescent marker can then bind to BrdU and the level of fluorescence can be measured to track the rate of neurogenesis. After the exposures, rats from both groups were euthanized over a period of four weeks. From the results, van Praag et al. found that though the short exposure rats exhibited elevated initial neuronal development, their neuronal survival rate was significantly lower as compared to the long exposure rats’ neuronal survival rate. Furthermore, the long exposure rats displayed lower yet more consistent rates of development. So, while brief exposures to new experiences lead to rapid growth, consistent exposure results in lasting neural tissue. The overall results from this study provide strong evidence that neuroplasticity results in neurogenesis.

The implications of neurogenesis and what it means for brain development still requires investigation. Preliminary research has shown that newly developed neurons often have not developed the structures (glutamatergic synapses) necessary for encoding memories. The implications of this finding suggest that hippocampal neurogenesis may be a proactive mechanism that produces neural cells in anticipation of encoding new memories. Further investigation into these questions may have an impact on the approach to developing preventative treatments for degenerative brain diseases.

References

1. M. Drew, C. Denny, Outsmarting (and Outrunning) Nature’s Harsh Decree. Nature Neuroscience 21(9), 12–25 (2017).  
2. H. Praag, et. al., Running Increases Cell Proliferation and Neurogenesis in the Adult Mouse Dentate Gyrus. Nature Neuroscience 2, 266–270 (1999).  
3. Image retrieved from: https://cdn.theatlantic.com/assets/media/img/mt/2018/03/RTR29JW9/lead_720_405.jpg?mod=1533691926