Researchers have identified specific neurons linked to ‘item memory,’ enhancing our comprehension of how the brain records and retrieves ‘what’ occurred, which may lead to new treatments for Alzheimer’s disease.
A team from the University of California, Irvine has pinpointed neurons that play a crucial role in “item memory,” expanding our knowledge of how the brain logs and recalls the particulars of events, which could pave the way for novel Alzheimer’s treatments.
Memories encompass three kinds of information: spatial, temporal, and item — essentially the “where, when, and what” of experiences. The formation of these memories is a complex process, involving the storage of information influenced by the meanings and outcomes of various experiences, which forms the basis of our ability to remember and share them.
The current study, published today in the journal Nature, is groundbreaking in illustrating the function of specific cells in the brain’s process of classifying and retaining new information, especially as it relates to rewards and punishments.
“Grasping this process is vital since it enhances our understanding of the fundamental workings of our brains, significantly in terms of learning and memory,” stated Kei Igarashi, the corresponding author and assistant professor of anatomy and neurobiology. “Our discoveries illuminate the intricate neural circuits that allow us to learn from our experiences and systematically store these memories.”
The researchers focused on the brains of mice, particularly the deeper layers of the lateral entorhinal cortex, where they found specialized neurons linked to item outcomes, crucial for learning. In these mice, particular odors served as important sensory signals for item memory. Certain neurons activated in response to a banana scent associated with a sweet water reward, while others reacted to the scent of pine linked to a bitter water negative outcome. This resulted in a mental map in the LEC categorized into these two groups.
On a structural level, the neurons in the deep-layer LEC are closely connected to neurons in the medial prefrontal cortex (mPFC). The team observed that neurons in the mPFC developed a similar mental map during the learning phase.
Additionally, when the activity of the LEC neurons was suppressed, mPFC neurons struggled to differentiate between positive and negative items, which hindered learning. Conversely, inhibiting mPFC neurons disrupted the LEC’s ability to distinguish between item memories, affecting both learning and memory recall. This indicates a co-dependent relationship between the LEC and mPFC, both working together to encode item memory.
“This research marks a significant step forward in our understanding of how the brain generates item memory,” noted Igarashi. “This insight opens new possibilities for exploring memory-related disorders like Alzheimer’s disease. Our findings suggest that item memory neurons in the LEC diminish in activity with Alzheimer’s. If we can find a method to reactivate these neurons, it could lead to targeted therapies.”
The leading authors of this research were graduate students Heechul Jun from the Medical Scientist Training Program and Jason Y. Lee from the Interdepartmental Neuroscience Program. Additional contributors included research technicians Nicholas R. Bleza and Ayana Ichii, along with postdoctoral researcher Jordan Donohue from Igarashi’s lab. Igarashi is affiliated with the Department of Biomedical Engineering and is also associated with the Center for Neural Circuit Mapping, the Center for the Neurobiology of Learning and Memory, and the Institute for Memory Impairments and Neurological Disorders.
This study received support from the National Institutes of Health, with various awards, as well as from the BrightFocus Foundation and UC Irvine’s Medical Scientist Training Program.
