What is Neurogenesis in the Brain?

Neurogenesis is the process by which new neurons are formed in the brain through pre-natal development and as adults.

This phenomenon primarily occurs in the hippocampus playing a crucial role in learning, memory, and cognitive flexibility.

Factors like exercise, enriched environments, and certain drugs can promote neurogenesis, while stress and aging may inhibit it.

Early Neurogenesis

Early neurogenesis begins during embryonic development. The neural plate, a flat sheet of cells that will become the nervous system, separates from the ectoderm. The ectoderm is the outermost of the embryo’s three tissue layers and also forms the skin and nervous tissue.

This split marks the start of neural development.

This separation occurs through a folding process that forms the neural groove.

The groove then fuses to create two key structures: the neural tube, which develops into the central nervous system, and the neural crest, a temporary group of cells.

Neural crest stem cells emerge from this structure and differentiate into various cell types that contribute to tissue and organ development.

These cells drive early brain growth. Neural stem cells are self-renewing cells that can divide to produce more stem cells or mature into neurons and glia.

During this early stage, they differentiate into specialized cell types at specific times and locations within the developing brain. This lays the groundwork for the brain’s future neurons.

Where Does Neurogenesis Happen?

In adults, neurogenesis primarily occurs in two brain regions:

• The subgranular zone (SGZ) of the hippocampus: Produces around 700 new neurons per day, helping support memory and learning.
• The subventricular zone (SVZ) near the brain’s lateral ventricles: sends new neurons to the olfactory bulb, which processes smells; this pathway is well established in rodents but much reduced in adult humans.

Emerging research suggests neurogenesis may also occur in the amygdala, a region linked to emotional memory, though this finding is still being explored.

Why is Neurogenesis Important?

New neurons play a critical role in brain plasticity—the brain’s ability to adapt and reorganize.

In the hippocampus, they help form new memories and enhance cognitive flexibility. In the amygdala, they may support emotional processing.

Neurogenesis also offers hope for brain repair. Animal studies show that after brain injury, neurogenesis increases, potentially aiding recovery.

Scientists are investigating how this could be harnessed to treat conditions like Alzheimer’s disease, depression, and traumatic brain injury.

How Does Neurogenesis Occur?

The Process of Neural Development

Neurogenesis begins when neurogenic signals trigger the activation of neural stem cells.

These signals can arise from various sources, including stimulated brain activity and environmental factors.

Once activated, neural stem cells either divide to maintain the stem cell population or differentiate into intermediate neural progenitor cells that are primed for maturation.

These progenitor cells then develop into either neurons or supporting glial cells, depending on the specific signals they receive.

Stages and Integration

As new neurons develop, they grow axons and dendrites—the branches that allow them to connect with other neurons.

These newly formed neurons must then survive and successfully integrate into existing brain circuits. This integration phase is crucial; if the new neurons fail to establish proper connections, they may undergo programmed cell death.

Successful integration allows these neurons to contribute to brain plasticity and adaptation.

Hippocampal Neurogenesis and Memory

In the hippocampus, astrocytes (a type of supporting brain cell) produce specific proteins that trigger neurogenesis.

Research has revealed that approximately 700 new neurons are born daily in the hippocampus, replacing a substantial share of these cells over a lifetime.

This continuous renewal process plays a vital role in forming new memories, but it can also affect existing memories in interesting ways.

Memory Storage and Transfer

When new neurons form in the hippocampus, they can temporarily disrupt memories already stored there.

This happens because memories initially form in the hippocampus but gradually transfer to other brain regions for long-term storage—a process that can take several years.

This effect appears to be temporary. During this transfer period, the formation of new neurons may weaken memories that haven’t yet fully transferred. This might explain why we struggle to retain memories from our early years.

How Our Understanding Has Evolved

For much of the 20th century, scientists believed neurogenesis ended after childhood.

A landmark rat study challenged this view.

Aim: Altman and Das (1965) tested whether new neurons are generated in the mammalian brain after birth.

Method: They injected rats with tritiated (³H) thymidine, a radioactively labelled DNA building block taken up by dividing cells, then used autoradiography to identify which cells had divided and where.

Findings: Newly generated cells, some with the appearance of neurons rather than glia, appeared in the dentate gyrus of the hippocampus in rats after birth.

Conclusion: New neurons are produced in the postnatal mammalian brain.

Evaluation: The technique could not yet prove a labelled cell was a neuron rather than glia, so the finding was dismissed for two decades. Paton and Nottebohm (1984) later showed adult-born neurons in canaries become electrically active, which helped reignite interest despite being in songbirds, not mammals.

Momentum for the idea was building.

It wasn’t until the 1990s that adult neurogenesis gained widespread acceptance.

Researchers like Richards, Kilpatrick, and Bartlett (1992) discovered neural stem cells in adult mouse brains, proving that even mature brains could generate new neurons.

The decisive step for human relevance came next.

Aim: Eriksson and colleagues (1998) turned to the human brain. Could the hippocampus, already known to be neurogenic in rodents and monkeys, also generate new neurons in humans?

Method: They obtained postmortem hippocampal tissue from five adult cancer patients who had received bromodeoxyuridine (BrdU) for diagnostic reasons, then used immunofluorescent staining to identify newly divided neurons.

Findings: BrdU-labelled cells that also carried neuronal markers turned up in the dentate gyrus of these adult patients, some of whom were in their seventies.

Conclusion: The adult human hippocampus can generate new neurons.

Evaluation: This was the pivotal demonstration that the rodent story extends to humans. The sample was small, just five patients, all with cancer and prior treatment that could affect cell division, so the number of new neurons detected was modest.

The Future of Neurogenesis Research

Understanding neurogenesis could lead to new treatments for cognitive decline and mental illness. Scientists are exploring:

• Activating dormant stem cells
• Transplanting neural cells into damaged areas
• Developing drugs that promote neurogenesis safely in humans

While most studies are still in early stages, the potential is promising.

Does Neurogenesis Decline With Age?

Yes, but it doesn’t stop completely. Neurogenesis declines gradually throughout life.

This “about a third” figure comes from one influential study using carbon-14 dating in human brain tissue (Spalding et al., 2013). Other researchers have reached very different conclusions about how much neurogenesis continues in the adult human brain (see Critical Evaluation, below).

Several factors can slow neurogenesis:

• Aging
• Chronic stress
• Poor sleep
• High blood sugar
• Sedentary lifestyle

Mental health conditions like depression and anxiety can also reduce neurogenesis.

Can You Boost Neurogenesis?

While we can’t reverse aging, certain habits can support neurogenesis at any age:

1. Physical Activity

• Aerobic exercise (like walking or cycling) boosts new neuron growth in the hippocampus.

2. Mental Stimulation

• Learning new skills, solving puzzles, or studying challenging material stimulates brain plasticity.

3. Nutrition

• Diets rich in flavonoids (e.g., blueberries, dark chocolate, green tea) support brain cell growth.

4. Sleep

• Quality sleep is essential for memory consolidation and neural repair.

5. Stress Reduction

Mindfulness, yoga, and relaxation techniques help lower cortisol, which otherwise inhibits neurogenesis.

Critical Evaluation

Neurogenesis is not without controversy, and how the field weighs its own evidence matters as much as the discoveries themselves.

The Adult Human Neurogenesis Debate

Whether the adult human brain generates new neurons is the field’s most contested question. High-quality studies have reached opposite conclusions. Much of the disagreement comes down to how the tissue was handled.

Sorrells et al. (2018) examined postmortem and surgical human hippocampal samples spanning fetal life to age 77. They stained it for immature-neuron markers.

They found young neurons early in life but none in the adult dentate gyrus. Their conclusion: human neurogenesis becomes vanishingly rare, or stops, after childhood.

Boldrini et al. (2018) and Moreno-Jiménez et al. (2019), published within months of Sorrells et al., used faster, gentler tissue processing. This preserves fragile, fast-degrading immature-neuron markers.

They found thousands of immature neurons in healthy adults into old age. The numbers declined only as Alzheimer’s disease progressed.

The likely explanation is methodological. Moreno-Jiménez et al. showed that prolonged fixation destroys the very markers Sorrells et al. relied on. A negative result can therefore reflect tissue handling, not a true absence of new neurons.

A 2018 consensus statement (Kempermann et al., 2018) found no compelling reason to abandon adult neurogenesis as a contributor to human brain function. It called instead for standardised methods.

The most likely picture is that adult human neurogenesis is real but modest. Its existence is better supported than its exact scale.

Strengths and Limitations

The evidence for neurogenesis, taken as a whole, has real strengths and real limits.

Strengths:

• Convergent animal evidence: birth-dating, stem-cell isolation, exercise studies, and direct recordings all point to the same conclusion in rodents.
• A concrete lifestyle mechanism: exercise and enrichment findings, backed by a human trial linking exercise to hippocampal volume, give “stay active” a real biological basis.

Limitations:

• Human evidence is mostly correlational: the strongest causal studies, linking neurogenesis to memory and antidepressant effects, were done in rodents, not people.
• Postmortem markers are fragile: immature-neuron markers degrade with tissue handling, so both positive and negative human findings need cautious reading.
• The effect is small and localised: even generous estimates put adult neurogenesis far too limited to repair large-scale brain damage on its own.

References

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