A new study from Trinity College Dublin, using immunological models of autism spectrum disorder (ASD) in rats, reveals the surprising role the maternal immune system plays in regulating access to memories of life’s earliest experiences in a condition known as amnesia of infancy.
The findings could help us both understand (and even access) these crucial periods and explain why some people with autism are able to recall memories from an age that most of us have long forgotten.
“Infantile amnesia is perhaps the most common but understudied form of memory loss in humans and mammals,” says Tomas Ryan, a neuroscientist at Trinity College Dublin.
“Despite its prevalence, the biological conditions underlying this amnesia and its effects on the engram cells that encode memories are poorly understood. As a society, we tend to assume that forgetting in young children is an inevitable fact of life and don’t pay much attention to it.”
Our mental autobiography usually begins somewhere between our second and third birthday. But it’s not that our brains are incapable of perceiving the world before this age. Studies in rats show that our brains can form memories at full capacity, storing them in a neurological library in structures called engrams.
Assuming that we no longer have the key to unlock the vaults that hold our earliest memories, researchers had to take into account the mechanisms that make these memories inaccessible.
There have been occasional clues. Infantile amnesia was prevented in rats by using drugs targeting specific neurotransmitters, as well as corticosteroids at certain times. This suggests that biochemical tides effectively erode pathways to long-term memories.
So Ryan and his research team turned their attention to environmental changes governed by the mother’s immune system.
Maternal immune activation (MIA), which is suspected to influence the emergence of traits associated with neurological conditions including ASD and schizophrenia, may also influence the pathways associated with infantile amnesia.
Using young and adult rats conditioned to fear electric shocks, the researchers compared rats born to mothers who elicited an immune response in mid-pregnancy.
While the male offspring of these mothers showed signs of social behavioral deficits like people with ASD, there was also evidence that they remembered fearful events much longer than their female siblings and control rats.
Further testing of transgenic mice carrying a gene that marks memory neurons revealed significant differences in the structure and size of engrams in a region of the hippocampus of MIA males called the dentate gyrus. These are known to be crucial in memory formation.
The most important part of the process appears to be a small immune protein called the cytokine IL-17a. Offspring born to mothers who had these proteins engineered away experienced infantile amnesia when the same immune responses were activated during pregnancy.
While it is unclear why mammalian brains have evolved a ‘forget button’ for the oldest memories, with the mechanisms at work now revealed, researchers are closer to understanding why memories remain accessible in some minds but are lost in others.
“The early developmental trajectories of our brains seem to influence what we remember and forget during our infancy,” says lead author Sarah Power, a neuroscientist at the Max Planck Institute for Human Development in Germany.
“We now hope to investigate in more detail how development affects the storage and retrieval of early childhood memories, a process that could have knock-on educational and medical implications.”
The research was published in Science Advances.