Molecular mechanisms of memory development in youth

Our brains undergo a fascinating process in developing the ability to create specific memories. In a groundbreaking preclinical study conducted at The Hospital for Sick Children (SickKids), researchers have potentially uncovered a molecular cause for changes in memory during early childhood.

When we talk about memories, we often refer to event-based memories or episodic memories. These are recollections tied to specific contexts, such as remembering a birthday party or a vacation. However, in young children, memories are more general or “gist”-like, lacking the specific context associated with event-based memories.

In a study published in Science, Drs. Paul Frankland and Sheena Josselyn, both Senior Scientists in the Neurosciences & Mental Health program at SickKids, have identified the molecular mechanisms that underlie the transition from gist-like to episodic memory in mice. This transition typically occurs between the ages of four and six in children. Understanding this change could provide valuable insights into child development research and various conditions that affect the brain, ranging from autism spectrum disorder to concussion.

The researchers used precise cellular interventions to explore the development of episodic memory at the molecular level, a novel approach that hadn’t been possible before. Dr. Frankland, who also holds a Canada Research Chair in Cognitive Neurobiology, expressed excitement about this advancement, emphasizing that while scientists have studied the development of episodic memory for many years, this study represents the first opportunity to examine the question at the molecular level.

By unraveling the molecular mechanisms involved in the development of episodic memory, this research brings us closer to understanding how our brains acquire the ability to create specific memories. This breakthrough may pave the way for further investigations into memory formation and its implications for child development and neurological conditions.

Growth of perineuronal net may trigger change in memory

In adults, memory traces or engrams are composed of approximately 10 to 20 percent of neurons. However, in young children, the size of these engrams is doubled, with 20 to 40 percent of neurons contributing to a memory engram.

So, what causes this change? The researchers focused on the hippocampus, a brain region crucial for learning and memory. Within the hippocampus, there are different types of neurons, including inhibitory cells called parvalbumin-expressing (PV) interneurons. These inhibitory cells play a role in constraining the size of engrams and facilitating memory specificity. The research team discovered that as these interneurons mature, memories transition from being general to becoming more specific, and engrams form at the appropriate size.

To delve deeper into the underlying mechanisms, the researchers utilized viral gene transfer technology developed by Dr. Alexander Dityatev, head of the Molecular Neuroplasticity research group at the German Center for Neurodegenerative Diseases. Their investigation revealed that as a dense extracellular matrix, called the perineuronal net, develops around these interneurons in the hippocampus, the interneurons mature, altering the way our brains create engrams and store memories.

Dr. Sheena Josselyn, who holds a Canada Research Chair in Circuit Basis of Memory, explains that once they identified the perineuronal net as a significant factor in interneuron maturation, they were able to expedite the net’s development and generate specific episodic memories in young mice, rather than general ones.

This research provides valuable insights into the molecular mechanisms that drive the transition from general to specific memory formation. By understanding how the development of inhibitory cells and the perineuronal net affects memory encoding, scientists may gain a deeper understanding of memory-related conditions and potentially develop new strategies for enhancing memory formation and specificity.

Informing new insights into brain function and cognition

While the team successfully induced the transition from gist-like to episodic memories by accelerating the development of the perineuronal net, they emphasize the significance of understanding the reasons behind the age disparity in memory types.

Adam Ramsaran, a Ph.D. candidate in the Frankland Lab and the study’s first author, explains that considering the purpose of memory, it is logical for a child’s memory to function differently from that of an adult. At the age of three, specific details may not be crucial. Gist-like memories allow children to build a broad knowledge base, which can become more specific as they grow older and accumulate more experiences.

Expanding on their molecular findings, the research team promoted the growth of the perineuronal net by providing an enriched environment, thus facilitating the formation of specific memories. This discovery has valuable implications for ongoing child development research at SickKids and the University of Toronto.

Dr. Frankland further notes that similar mechanisms of maturation are observed in various sensory systems of the brain, extending beyond memory development. This suggests that the same brain mechanism may be utilized by different brain regions for diverse purposes. Such findings open up exciting opportunities for further research and collaboration.

By delving into the underlying processes of memory formation and its age-related changes, this study not only sheds light on the developmental aspect of memory but also has the potential to contribute to broader investigations into sensory systems and brain function.

Source: The Hospital for Sick Children