New study reveals how childhood memories change at a cellular level

The study sheds light on the role of inhibitory cells and the maturation of interneurons in memory specificity. This breakthrough opens doors for understanding brain function.
Abdul-Rahman Oladimeji Bello
Impression of neurons firing in a brain

Do you remember what you had for breakfast yesterday? Or the time you rode a roller coaster for the first time? Our ability to create specific memories is a fascinating aspect of human cognition. But have you ever wondered how our brains develop this remarkable capability?

Researchers at The Hospital for Sick Children (SickKids) have taken a significant step towards unraveling this mystery. In one of the first preclinical studies to examine memory development in young individuals, they may have discovered a molecular cause for memory changes during early childhood.

When we think of memory, we often envision event-based memories, also known as episodic memories. These memories are tied to specific contexts and allow us to recollect experiences vividly. 

However, for young children, memories are more general or "gist"-like. These general recollections are typically not associated with a specific context.

Led by Drs. Paul Frankland and Sheena Josselyn, both senior scientists in the Neurosciences & Mental Health program at SickKids, the research team published a groundbreaking study in the journal Science this week. 

They successfully identified the molecular mechanisms that underlie the transition from gist-like to episodic memory in mice. This finding may have broad implications for child development research and shed light on conditions that affect the brain, ranging from autism spectrum disorder to concussion.

"Researchers have studied how episodic memory develops for decades, but thanks to the development of precise cellular interventions, we were now able to examine this question at the molecular level for the very first time," says Dr. Frankland, who also holds a Canada Research Chair in Cognitive Neurobiology.

Engrams, the composition of memory traces

The team made a remarkable discovery about the composition of memory traces, also known as engrams. In adults, engrams are composed of 10 to 20 percent of neurons. 

However, in young children, these engrams are twice as large, with 20 to 40 percent of neurons contributing to a memory. But what causes this change?

The hippocampus, a brain region crucial for learning and memory, houses various types of neurons, including inhibitory cells called parvalbumin-expressing (PV) interneurons. 

These interneurons play a vital role in constraining the size of engrams and enabling memory specificity. The researchers found that as these interneurons mature, memory transitions from a general to a more specific form, with engrams formed at the appropriate size.

Driven by their findings, the researchers decided to dig deeper and explore the underlying reason for this change. They utilized viral gene transfer technology developed by Dr. Alexander Dityatev from the German Center for Neurodegenerative Diseases. 

Their investigations revealed that a dense extracellular matrix, called the perineuronal net, develops around the PV interneurons in the hippocampus. It triggers their maturation. Consequently, this shift in the brain's structural environment influences how engrams are created and memories are stored.

Dr. Josselyn, who holds a Canada Research Chair in Circuit Basis of Memory, explains, "Once we identified the perineuronal net as a key factor in interneuron maturation, we were able to accelerate the net's development and create specific episodic, rather than general, memories in juvenile mice."