New Year, New Neurons: The History of Neurogenesis

By Mary Cooper

“New year, new me,” is a thought we may have had around the start of a new year. Maybe we want to be stronger, healthier, or smarter and make a well-intentioned resolution to finally reach our goals. Maybe we succeed or maybe we fail, but regardless of whether we stick to our resolutions, there is one thing that will change by the end of 2023: your brain.

Maybe we succeed or maybe we fail, but regardless of whether we stick to our resolutions, there is one thing that will change by the end of 2023: your brain.

Each year, our brains make new cells and look different from the year before. However, the scientific community was not easily convinced of this and there is even still controversy over this finding. As we enter the new year, let us look back at a brief history of how we came to accept the fact that brains change every year just like the rest of us.

It is currently accepted that we make new brain cells throughout our entire lives, though this is still a topic of hot controversy as it is hard to thoroughly study cells functioning in living humans (Hao et al., 2022). These brain cells are created through adult neurogenesis: the process by which neurons are generated from neural stem cells in the adult brain. To get a better understanding of why and how we learned that the brain makes new cells as adults through neurogenesis, let us briefly go over the scientific history of neurogenesis research.

As a first step towards understanding cellular biology, scientists began looking at cells through early microscopes to make the observation that cells “copy & paste” themselves by replicating their genes and dividing into identical copies. This copying and pasting is the same mechanism as adult neurogenesis, but when the cells are outside of the nervous system we simply call this replication “cellular division”. Cellular division occurs every day in order to make new cells in the body, both in the brain and in other organs. This process of cellular division in cells outside of the nervous system (somatic cells) was first observed in the early 1800’s. Scientists at this time knew that some cells make more copies of themselves constantly. For example, our skin cells need to continuously replicate all day long in order to heal injuries, like scratches, and keep our skin strong. After learning about cellular division in the body, researchers soon started asking themselves the critical question: do brain cells, too, copy and paste themselves like we have seen in somatic cells? For a while, the answer by the scientific community was “no”’; we assumed that our brain cells stayed the same from one year to the next and did not replicate.

One of the earliest questions about the brain was whether it was composed of a continuous net of neural tissue, or of individual cells closely assembled together. In the late 1800’s Santiago Ramón y Cajal’s work the brain as composed of individual brain cells, the scientific community to accept idea now known as the “neuron doctrine”. While this portion of his theory is still viewed as correct, he also theorized that brain cells are done replicating by the time we reach adulthood. In 1891 , the scientific community agreed with Cajal’s proposed theory that the brain had all of the cells it needed by the time a person reaches adulthood (Palmer, 2013). This theory was summarized by Cajal himself: “In the adult…the nerve paths are something fixed, ended, and immutable. Everything may die, nothing may be regenerated” (Cajal, 1928). In other words, we thought once we reach adulthood, our brain stops making new cells.

One of the earliest questions about the brain was whether it was composed of a continuous net of neural tissue, or of individual cells closely assembled together.

In 1962, more than 70 years after the neuron doctrine was first posited, a researcher named Joseph Altman gained attention after he suggested that brain cells continue replicating into adulthood. In Altman’s study, he observed that new brain cells were being produced in the brains of adult rodents (Altman, 1962). This finding directly contradicted the current theories on neurogenesis established by previous publications, such as the neuron doctrine. Unfortunately, this research was ignored for almost two decades and the misunderstanding about adult neurogenesis continued even after Altman’s discoveries.

Thus, the conversation about adult neurogenesis was stalled until three decades later after a series of studies published the discovery of neural stem cells, a type of brain cell that continues to develop their form and function into adulthood. These studies used the brains of mice to establish that stem cells change themselves daily to regenerate, repair, and perform necessary functions in the brain, not only during fetal development, but also into adulthood (Kilpatrick & Bartlett, 1993; Palmer et al., 1995; Reynolds & Weiss, 1992). These cells and their ability to choose their shape and job in the brain showed scientists that the brain’s cells were capable of change and differentiation after childhood development. This groundbreaking finding revitalized the conversation of adult neurogenesis and gave the theory the validity it needed for further research. Years of subsequent experiments in animals and humans revealed that not only does the brain have stem cells that can change shape and function as needed, but that adult brain cells can also make copies of themselves without using stem cells through a process of neurogenesis that occurs in two specific areas of our brain (Kempermann et al., 2018).

These two regions that have the unique ability to divide and be integrated with other cells are structures called the dentate gyrus (DG) in the hippocampus, and an area under the fluid-filled spaces in the brain called the lateral sub-ventricular zone (SVZ; Kumar et al., 2019). The hippocampus is a structure specialized for spatial memory, among other functions. Hippocampal cells wire themselves to make memories of the things we have experienced and learned in those situations (Abrous & Wojtowicz, 2015). Storing updated information about the environment and memories we have associated with it requires higher degrees of neuroplasticity; that is, the creation of new brain cells keeps pace with our ever-growing memory. The SVZ plays a similar role in the olfactory system, the bodily structure that controls the sense of smell. In the SVZ, new cells are made and transferred to the olfactory system above the nose, where cells can be replaced and form connections according to different combinations of odorants. These cells are directly exposed to our nasal passage, where they are replaced often to prevent damage and promote memory formation with smells, as smell is a strong mediator of memory formation and recall (Abrous et al., 2005). The result of nearly two centuries of work has made adult neurogenesis a widely accepted theory for how our brain cells continue to replicate in order to form new memories and develop throughout our lives.

In summary, we have come a long way in the scientific community’s discussions and discoveries about adult neurogenesis. In fact, in the past decade we have discovered that the brain makes up to 700 new cells in the hippocampus every day (Spalding et al., 2013). While it took researchers a few decades to come to these conclusions, we can learn valuable lessons from the power of the scientific process and our brain. Even if there might not be a “new you” in 2023, there will be new brain cells. This is for sure a good reason to celebrate!

Even if there might not be a “new you” in 2023, there will be new brain cells. This is for sure a good reason to celebrate!

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Written by Mary Cooper
Illustrated by Vidya Saravanapandian
Edited by Johanna Popp, Carolyn Amir, and Lauren Wagner

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References
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