Revealing Neural Basis of Categorizing and Remembering Novel Information

Scientists at the University of California, Irvine have pinpointed the brain cells involved in remembering specific details of events. This breakthrough sheds light on how human brains store and recall information and offers potential new targets for Alzheimer's disease research.

Memories include three categories of details: temporal, spatial, and item details, or the "where, when, and what" of an event. The intricate process of creating them entails preserving data derived from the interpretations and consequences of various encounters, which serve as the basis for the human capacity to recollect and narrate these experiences.

The study is the first to identify the function of particular brain cells in the categorization and memory of novel information, especially when it is associated with rewards or penalties. The study was published in the journal Nature.

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.”

Kei Igarashi, Study Corresponding Author, Chancellor Fellow, and Associate Professor, Department of Anatomy and Neurobiology, University of California, Irvine

Scientists examined the brains of mice, concentrating on the lateral entorhinal cortex's deeper layers. It was there that they found specialized item-outcome neurons that are crucial for learning. In mice, odors are important sensory cues for item memory.

When exposed to the smell of bananas, some neurons fired up in response to a sucrose water reward. The scent of pine correlated with a negative bitter water outcome in other neurons. In the LEC, a mental map that was split into those two categories was created.

Anatomically, neurons in the medial prefrontal cortex and neurons in the deep-layer LEC are closely connected. During the learning process, team members noticed that neurons in the mPFC formed a similar mental map.

They also discovered that learning was hampered when LEC neurons' activity was suppressed because the mPFC neurons were unable to identify positive from negative stimuli. Learning and item memory recall were severely hampered when the mPFC neurons were inhibited, as this completely interfered with the LEC's capacity to keep item memories apart. This information demonstrated the co-dependence of the LEC and mPFC in the encoding of 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.”

Kei Igarashi, Study Corresponding Author, Chancellor Fellow, and Associate Professor, Department of Anatomy and Neurobiology, University of California, Irvine

Graduate students Heechul Jun from the Medical Scientist Training Program and Jason Y. Lee from the Interdepartmental Neuroscience Program were the two main authors of this work. Jordan Donohue, a Postdoctoral Researcher from the Kei Igarashi lab, and research technicians Nicholas R. Bleza and Ayana Ichii were also part of the team.

Igarashi is a member of the Institute for Memory Impairments and Neurological Disorders, the Center for Neural Circuit Mapping, the Center for the Neurobiology of Learning and Memory, and the Department of Biomedical Engineering as well as a joint faculty member.