Eric Swanson, Economist, University of California, Irvine | University of California, Irvine
Eric Swanson, Economist, University of California, Irvine | University of California, Irvine
Researchers from the University of California, Irvine have identified neurons responsible for "item memory," a significant discovery that enhances understanding of how the brain stores and retrieves specific details. This breakthrough offers a potential new target for treating Alzheimer's disease.
Memories consist of spatial, temporal, and item details—the "where, when, and what" of an event. The study published in Nature is the first to reveal the role of specific cells in classifying and remembering new information linked to rewards or punishments.
"Understanding this process is crucial because it deepens our insight into the fundamental way our brains function, especially in learning and memory," said corresponding author Kei Igarashi, Chancellor’s Fellow and associate professor of anatomy and neurobiology. "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."
The research focused on mice brains' deeper layers of the lateral entorhinal cortex (LEC), where specialized item-outcome neurons essential for learning were discovered. Odors served as critical sensory cues for item memory in mice. Neurons activated by banana scent associated with sucrose water reward contrasted with those responding to pine smell linked to bitter water negative outcome. This formed a mental map divided into two categories within the LEC.
Anatomically, deep-layer LEC neurons are closely connected with medial prefrontal cortex (mPFC) neurons. Researchers observed that mPFC neurons developed a similar mental map during learning. When LEC neuron activity was inhibited, mPFC neurons failed to distinguish between positive and negative items, impairing learning. Conversely, inhibiting mPFC neurons disrupted LEC's ability to keep item memories separate, affecting both learning and recall.
"This study is a significant advancement in our understanding of how item memory is generated in the brain," Igarashi said. "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."
Graduate students Heechul Jun from the Medical Scientist Training Program and Jason Y. Lee from the Interdepartmental Neuroscience Program led this work alongside research technicians Nicholas R. Bleza and Ayana Ichii, postdoctoral researcher Jordan Donohue from Kei Igarashi lab among others.
The study received support from National Institutes of Health awards R01MH121736, R01AG063864, R01AG066806, R01AG086441; BrightFocus Foundation grant A2019380S; UC Irvine Medical Scientist Training Program grant T32GM008620.
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