Microglia shown to shape infantile amnesia in mice, study reported

A recent study has reported that microglia, the brain’s resident immune cells, play a central role in infantile amnesia in mice, with implications for how memories are stored, suppressed and retrieved across the lifespan

Babies of every studied mammalian species, from mice to humans, rapidly forget experiences from early life, a phenomenon known as infantile amnesia. A recent study has reported evidence that microglia – the primary immune cells of the brain – regulate this early-life forgetting in mice.

Led by Trinity College Dublin scientists, the research examined how suppressing microglial activity in very young mice influenced memory retention. Infancy and early childhood are periods of rapid brain development during which individuals acquire vast quantities of information. Despite this intense learning, most people lack episodic memories from this stage of life, such as recollections of early celebrations or first days in formal education.

To investigate the biological basis of this apparent contradiction, the researchers inhibited microglial activity in infant mice and assessed their ability to remember a fearful experience later in life. They also analysed markers of microglial activity in two brain regions that are central to memory formation and emotional processing, the dentate gyrus of the hippocampus and the amygdala.

The study reported that reduced microglial activity in these regions was associated with stronger memory retention. Young mice with suppressed microglial function showed improved recall of the fearful experience compared with control animals. The researchers also labelled engram cells, neurons whose activity corresponds specifically to memory encoding and retrieval. When microglial activity was inhibited, these engram cells showed greater activation, which suggested that memory traces remained more accessible.

Earlier work by the same group had shown that mice born to mothers with activated immune systems did not display typical infantile amnesia. In the current study, when researchers suppressed microglial activity in these offspring, they restored infantile amnesia, which suggested a re-establishment of typical memory suppression mechanisms. While other cell types may also contribute, the findings indicated that microglia are required for infantile amnesia in mice and play a role in shaping the neural networks that support memory.

“Microglia, the resident immune cells of the central nervous system, can be considered as 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,” said Dr. Erika Stewart, the study’s first author.

“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,” added co-author Professor Tomás Ryan.

“But what if those memories are still present in the brain?” Ryan said. He explained that memory researchers increasingly view forgetting as an active feature of brain function rather than a failure. In this framework, the brain stores memory engrams in a way that limits their expression until they are needed.

The findings suggested that microglia help to organise how these engrams are stored and accessed throughout life. Understanding the biology of infantile amnesia could therefore provide broader insight into how forgetting operates in the brain more generally and how learning and forgetting to interact during early development.

“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,” Ryan said.

For further reading please visit: 10.1371/journal.pbio.3003538