Blocking immune cells in the brain can prevent infant forgetting

Scientists have found that blocking microglia (specialist immune cells in the brain) prevents infant forgetting (“infantile amnesia”) and improves memory in mice, suggesting that microglia may actively manage memory formation and dictate what, and when, we forget.

Infants of many species from mouse to human rapidly forget things that happen to them—a phenomenon called infantile amnesia -- but until now we have known little about how this happens. The new discovery, just published in leading international journal PLOS Biology, now offers strong support for the mechanism at play.

Infants and young children are growing rapidly and taking in vast amounts of information as they develop, but there is a lack of episodic memory from this early period of life, like memories of past events such as a first birthday party or first day of playgroup. 

To better understand how this infantile amnesia functions, the authors of this study inhibited the activity of microglia, which are the main immune cells of the brain, in very young mice and examined how well they could remember a fearful experience. They also examined microglia markers in two memory-related brain areas: the dentate gyrus of the hippocampus and the amygdala. 

The researchers found that when microglia activity was suppressed, with less activity in the hippocampus and amygdala, young mice had better memories of their fearful experiences. 

The scientists also used glowing tags to identify engram cells, which are neurons whose activity is specifically associated with memory formation. When microglia were inhibited in infant mice, the engram cells were more activated, offering a functional explanation for the enhanced memory recall. 

In previous work, the scientists found that mice born to mothers with activated immune systems do not have infantile amnesia, but when they modulated microglial activity during an early postnatal window soon after birth in these mice, they were able to restore the normal state of infantile amnesia.

In combination, while other cell types might also be involved, the authors suggest that microglia are required for infantile amnesia in mice and could help shape the networks that form memories in the brain.

Lead author, Dr Erika Stewart, is a Postdoctoral Research Scientist at Columbia University Irving Medical Center, USA. She conducted this work for her PhD under the supervision of Prof. Tomás Ryan, from Trinity College Dublin’s School of Biochemistry and Immunology.

Dr Stewart said: “Microglia, the resident immune cells of the central nervous system, can be considered the ‘memory managers’ in the brain. Our paper highlights their role in infantile amnesia specifically and indicates that common mechanisms may exist between infantile amnesia and other forms of forgetting – both in everyday life and in disease.” 

Senior author, Prof. Ryan, added: “Infantile amnesia is possibly the most ubiquitous form of memory loss in the human population. Most of us remember nothing from our early years of life, despite having so many novel experiences during these formative years. This is an overlooked topic in memory research, precisely because we all accept it as a fact of life.” 

“But what if those memories are still present in the brain? Increasingly, the memory field views forgetting as a 'feature' of the brain rather than a 'bug'. It seems that the brain is filing away the neuronal units that store memory, the engrams, for later use and that microglia seem to be functioning in the brain to help organise how engrams are stored and expressed across the lifetime.” 

“The biology of infantile amnesia may give us insight into how forgetting happens in the brain in general. Furthermore, being able to manipulate infantile amnesia opens doors into new ways of imagining how learning, and forgetting, might work during the early years of life. It will be interesting and important to identify humans that don’t experience infantile amnesia, to learn how their brains work, and understand their experience of early childhood education.”

One of the remaining burning questions is whether there is an adaptive (useful) purpose to infantile amnesia. It seems to only be a feature in “altricial” mammals, which are those that are born in a helpless, vulnerable state and are completely reliant on their caregiver(s). “Precocial” mammals such as guinea pigs, born in a more advanced state of maturation with greater independence, do not display infantile amnesia. 

Perhaps memories formed while individuals are so helpless are not as reliable and they are stored away under the shroud of infantile amnesia, but the scientists underline nobody yet knows the answers here. 

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