Adult neurogenesis: How do we learn and remember?

We’ve all heard the saying that we “learn as we grow’…but is it really true?

(Cover Image - Source: Pixabay (User: geralt))

“When do our brains stop growing?” is a question without a conclusive answer. Whilst the exact time will vary from person to person, it has been widely accepted that our brains will have completely developed once we reach our mid-twenties. However, as with most common beliefs, the scientific community is challenging this dogma.

One such challenge to this belief is adult hippocampal neurogenesis (AHN) - the process, whereby new neurons (the archetypal cells of the brain, which transmit information throughout our bodies) are continuously reproduced, throughout our lifetime in the hippocampus, a key part of the inner brain, which is known to control our memories. Whilst AHN is well-established in mice, it has been questioned whether it could be translated in humans. Recent evidence suggests it can.

Using fluorescent ‘reporter’ chemicals, which glow up when they attach to their biological targets, three separate studies (by Boldrini, Moreno-Jimenez and Tobin) discovered that pools of neural progenitor cells (the precursors to neurons) and young neurons, primed for adult development, are present in the dentate gyrus (DG) of human hippocampuses till up to 90 years of age. In fact, it is believed that around 700 adult-born neurons are generated each day – equating to a yearly turnover of 1.75 per cent of the human DG!

Adult-born neurons are unique as they originate from reprogrammed (quiescent) progenitor cells - once they receive a signal to reproduce, these progenitors will re-enter the cell cycle, where they build up from a renewable stem cell, into their final adult form. AHN takes around 6 weeks, on average, to occur (Image created using Biorender)

So adult-born neurons exist in the human brain, but what do they do? The answer is based upon their location - the dentate gyrus. The DG is the memory co-ordinator of the hippocampus. It is responsible for recognising whether any incoming signals (stimuli) have been encountered before, and decides how the hippocampus should respond. If the stimulus has previously been encountered, then the DG can connect it to an existing neural network, which contains an appropriate, pre-existing memory – this is called pattern completion. However, if the stimulus is brand new, the DG will link it to a new network, which carries out a new response – this is known as pattern separation.

Adult-born neurons are important for pattern separation as they form the networks, which are activated in place of the existing networks, to encode new memories. Repeated exposure to a specific stimulus will cause the associated neural network to remain continuously active, which improves signal flow along the circuit, and results in quicker responses. This concept is known as long-term potentiation and can be related to our everyday lives: the more we memorise a fact for a test, for example, the more active the associated network will be. As we keep on using this neural circuit, the information flow will become more efficient, allowing us to recall the fact more quickly. Combining pattern separation and long-term potentiation explains how we can recognise, and then adapt to, new situations and environments.

Adult-born neural networks don’t just work independently of the existing networks; in some cases, they can suppress them, through indirect connections to inhibitory intermediate neurons. This can lead to similar memories being ‘overwritten’ over each other (Image created using Biorender)

Adult-born neurons are not just useful for learning and remembering – they are also good indicators of medical conditions. The levels of AHN have been linked to psychiatric conditions, such as depression and anxiety. Reduced AHN, which is commonly seen in clinical depression, can disrupt our ability to separate patterns. This may lead to ‘over-generalisation’ – where we keep on linking a certain event or environment, to a specific experience or emotion, without looking back at our other experiences.

The clinical applications of AHN also extend to neurological conditions, such as Alzheimer’s disease – a condition, which usually arises in the hippocampus. With Boldrini, Moreno-Jimenez and Tobin all showing that the rate of AHN decreases with age, a reduction of AHN could be a potential cause of the memory loss and impairment, which are associated with these age-related conditions.

It is clear that AHN has an impact on our health and wellbeing… so can we do anything about it? It appears so. Whilst highly beneficial to our physical health, regular exercise is also known to promote the production of neural growth factors within our brains, and for improving memory and cognition, in general. Our ability to think may also be affected by what we eat, with recent evidence suggesting that our brains may favour a Mediterranean-style diet.

On the flipside, it has been shown that reduced AHN can negatively impact our resilience to stress. This might be why we often think more pessimistically when we are stressed out, as our minds become fixed on the negative situation. Restoring AHN, and our ability to separate patterns, could explain how stress-coping techniques, like meditation, allow us to think more clearly, and look for alternative solutions to overcome these challenging situations.

AHN may therefore provide clues to many unanswered areas of neuroscience. Could learning about how our brains grow, in fact, be growing our brains?