University of California, Irvine researchers have identified the neurons involved in “item memory,” expanding on our knowledge of how the brain stores and recalls the specifics of “what” happened and providing a novel therapeutic target for Alzheimer’s patients.
Memories include three types of details: spatial, temporal and item, the “where, when and what” of an event. Their creation is a complex process that involves storing information based on the meanings and outcomes of different experiences and forms the foundation of our ability to recall and recount them.
“Understanding this process is crucial because it deepens our insight into the fundamental way our brains function, especially in learning and memory. Our findings shed light on the intricate neural circuits that enable us to learn from our experiences and store these memories in a structured way,”
said corresponding author Kei Igarashi, Chancellor’s Fellow and associate professor of anatomy and neurobiology.
The study is the first to reveal the role of specific cells in how the brain classifies and remembers new information, particularly when linked to rewards or punishments.
Deep Lateral Entorhinal Cortex
Researchers examined mouse brains, focusing on the deeper layers of the lateral entorhinal cortex, where they revealed specialized, item-outcome neurons required for learning. Odors are important sensory cues for item memory in mice.
Some neurons became active when exposed to the scent of banana, associated with a sucrose water reward. Other neurons responded to the smell of pine, associated with a bitter water negative outcome. A mental map divided into those two categories was formed in the lateral entorhinal cortex (LEC).
Anatomically, neurons in the deep-layer LEC are closely linked to neurons in another brain region, the medial prefrontal cortex. Team members discovered that neurons in the mPFC formed a similar mental map during the learning process.
Disrupted Item Memory Separation
They also found that when the activity of the LEC neurons was inhibited, those in the mPFC failed to properly distinguish between positive and negative items, leading to impaired learning.
Conversely, when the mPFC neurons were inhibited, the ability of the LEC to keep item memories separate was totally disrupted, impairing learning and item memory recall. This data indicated that the LEC and mPFC are co-dependent, working together to encode item memory.
“This study is a significant advancement in our understanding of how item memory is generated in the brain. This knowledge now opens up new avenues for investigating memory disorders, such as Alzheimer’s disease. Our data suggests that item memory neurons in the LEC lose their activity in Alzheimer’s. If we can find a way to reactivate these neurons, it could lead to targeted therapeutic interventions,”
Igarashi said.
The study was supported by the National Institutes of Health; BrightFocus Foundation; and a UC Irvine Medical Scientist Training Program grant.
Reference:
- Jun, H., Lee, J.Y., Bleza, N.R. et al. Prefrontal and lateral entorhinal neurons co-dependently learn item–outcome rules. Nature (2024). Doi: 10.1038/s41586-024-07868-1