Why You Can't Remember Being a Baby: Immune Cells as Memory Janitors

Try to remember your first birthday party. You can probably conjure up a vague image based on a photograph your parents showed you a thousand times. That mental image is most likely false. The truth is that most people barely remember anything before their 3rd birthday. It’s a phenomenon called infantile amnesia, and it’s one of the great paradoxes of being human. We spend our early years soaking up information like sponges, yet our brains seem determined to hit the “delete” button on almost all of it. For a long time, neuroscientists treated this forgetting as a cognitive glitch or a simple lack of brainware maturity. But a new study suggests that infantile amnesia is actually a feature, not a bug—and it’s being run by an unexpected crew of cellular janitors. It turns out that microglia, the brain’s resident immune cells, might be actively scrubbing away our earliest memories. The Brain’s Memory Managers We typically think of the immune system as our body’s defense force, hunting down pathogens and clearing out debris. But in the brain, immune cells have a day job that looks a lot more like IT management. Microglia are specialized macrophages that account for about 10-15% of cells found within the brain. During the rapid development of infancy, they are busy pruning synapses—the connections between neurons—to refine brain circuits. Researchers at Trinity College Dublin wanted to know if this pruning process was responsible for the loss of early memories. They worked with infant mice, which, like humans, naturally forget fearful experiences they learned as babies . The team, led by Erika Stewart and Tomás Ryan, trained 17-day-old mice to associate a specific box with a mild foot shock. Under normal conditions, these mice would forget this scary experience by the time they were 25 days old. Essentially, they would grow out of the memory. But when the scientists fed the mice minocycline—an antibiotic that inhibits microglial activity—something remarkable happened. The mice didn’t forget. Even eight days later, a lifetime in mouse infancy, the treated mice froze in fear when placed back in the box. By telling the immune system to take a break, the researchers had effectively stopped infantile amnesia in its tracks. Glowing Traces of the Past To prove that the memories were physically still there, the team used a technique called genetic “tagging” to make the specific neurons holding the memory—known as “engrams”—glow with a fluorescent protein (EYFP). This allowed them to literally see the memory trace in the brain. They focused on the dentate gyrus of the hippocampus, a hub for context memory, and the amygdala, the brain’s emotional center . In the mice with active microglia (the ones that forgot), the memory engrams were less active during recall. But in the mice treated with the inhibitor, the memory engrams in the amygdala lit up with activity. The memory files hadn’t been corrupted; they had just been protected from the shredder. When the researchers looked closer at the cellular level, they saw that inhibiting the microglia changed how these immune cells interacted with the memory neurons. In the treated mice, there were fewer contact points between the microglia and the engram cells . Essentially, by keeping the “memory managers” at arm’s length, the memory was preserved. “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,” explained Dr. Stewart, now a Postdoctoral Research Scientist at Columbia University. The Autism Connection The study didn’t stop at just blocking forgetting. The researchers also looked at the flip side: what happens when the brain’s immune system is primed too early? There is a known link between maternal inflammation during pregnancy and neurodevelopmental conditions like autism-spectrum disorder (ASD). In previous work, this same team discovered that male mouse offspring born to mothers with activated immune systems (a model called MIA, or maternal immune activation) don’t experience infantile amnesia. They remember things they should forget. In this new study, they found that these MIA mice had microglia that looked “blunted,” with reduced phagocytic (eating) activity . It was as if their cellular janitors were on strike. Here’s the twist: When the researchers gave these MIA mice minocycline very early in life (from birth to day 14), it seemingly “reset” their microglia. The treatment restored their ability to forget. It suggests that for the brain to develop typical forgetting patterns, the immune system needs to be functioning within a “Goldilocks” zone—not too active, but not too dormant either. A Feature, Not a Bug Why would evolution design a brain that deletes its own data? Senior author Prof. Tomás Ryan suggests that forgetting is a crucial part of how we learn. “Infantile amnesia is possibly the most ubiquitous form of memory loss in the human population,” Ryan notes. “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.” Ryan adds, “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. Microglia seem to be functioning in the brain to help organise how engrams are stored and expressed across the lifetime.” The implications here are huge. If we can chemically toggle the ability to access early memories in mice, we are one step closer to understanding how memory persistence works in humans. It also raises fascinating questions about neurodiversity. Ryan notes, “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.” For now, if you can’t remember your second birthday, don’t worry. It just means your microglia were doing their job, diligently sculpting your brain to be ready for the world.