The human brain has the extraordinary ability to quickly distinguish a stranger from someone familiar, even while simultaneously being able to remember details about someone over decades of encounters. Now, in studies of mice, scientists at Columbia’s Zuckerman Institute have revealed how the brain elegantly performs both tasks.
“These findings are the first evidence that a single population of neurons can use different codes to represent novel and familiar people,” said co-corresponding author Stefano Fusi, PhD, professor of neuroscience at Columbia’s Vagelos College of Physicians and Surgeons. principal investigator. at Columbia’s Zuckerman Institute and a member of Columbia’s Center for Theoretical Neuroscience.
In a paper published today at Neuron, Columbia scientists investigated social memory, the ability to remember encounters with others. This form of memory consists of two distinct mental processes—discriminating between new and familiar individuals and recalling details about those that are recognized.
We can easily determine if someone is familiar, but may struggle to remember the details of where and how we know them, especially when we meet them out of context.”
Steven A. Siegelbaum, PhD, co-corresponding author, Chair of the Department of Neuroscience at Columbia’s Vagelos College of Physicians and Surgeons
Previous work has struggled to pinpoint how the brain performs both tasks, given their conflicting demands. The ability to detect whether someone is familiar or not must be applied to many different locations and events, whereas recollection involves recalling many specific experiences about a given person.
In the new study, the scientists investigated a brain region called CA2, part of the hippocampus, a pair of hippocampus-shaped brain structures essential for memory. Dr. Siegelbaum previously made the groundbreaking discovery that CA2 neurons are particularly important for social memory.
The researchers analyzed the mice’s brains using calcium imaging, a technique that relies on genetically engineered cells—in this case, in CA2—that rapidly change color when active. Calcium imaging allowed Lara Boyle, a former MD-PhD student in the Siegelbaum lab and co-first author of the study, to know precisely which neurons they were examining.
“This helped clear up uncertainty from previous research in distinguishing mouse brain responses to novel and familiar subjects,” said Dr. Siegelbaum, Gerald D. Fischbach, MD, Professor of Neuroscience and Pharmacology, and Principal Investigator at the Zuckerman Institute.
The scientists recorded for the first time how the rodents’ CA2 cells responded when they were exposed to either a pair of strangers or a pair of familiar relatives. They then used computational methods, led by the team of Dr. Fusi, to analyze the pattern of activity in about 400 to 600 neurons in CA2.
The scientists discovered that the same population of neurons encoded memories of both familiar and unfamiliar individuals. Unexpectedly, the neurons used different patterns of activity depending on a mouse’s level of familiarity with another rodent.
When the mice were exposed to other mice they were unfamiliar with, the resulting activity in CA2 was relatively simple, or, in the scientists’ parlance, “low-dimensional.” It’s like several members of an orchestra playing the exact same notes, Dr. Fousi explained. In contrast, exposure to familiar relatives led to more complex, high-dimensional CA2 activity, as if they were all playing different tunes.
The researchers’ calculations and simulations suggest that more complex or higher-dimensional neural activity can help the brain encode detailed memories of past encounters with familiar people. In contrast, simpler or lower-dimensional activity can help the brain reliably recognize new people in different environments.
“When you meet someone new, you can use abstract categories to describe them in your head — for example, this is a kid, with brown hair, red backpack,” said postdoctoral research associate Lorenzo Posani, PhD, co-first author in the study that led to the computational analysis. “Then, as you get to know them, they become a specific person and personality.”
This fundamental discovery about how details about others are encoded may shed light on disorders that affect memory.
“When we look at different mouse models of human diseases such as schizophrenia or Alzheimer’s that are known to affect memory, we can now ask more precisely how the neural activity that supports familiarity detection and recall might be altered,” said Dr Siegelbaum. “We hope that what we’ve learned can lead to a better understanding of the types of interventions that can rescue memory deficits in these disorders.”
The paper, “Tuned geometries of hippocampal representations meet the computational demands of social memory,” was published online at Neuron in TK, 2024.
The full list of authors includes Lara M. Boyle, Lorenzo Posani, Sarah Irfan, Steven A. Siegelbaum, and Stefano Fusi.
Source:
Journal Reference:
Boyle, LM, et al. (2024) Tuned geometries of hippocampal representations meet the computational demands of social memory. Neuron. doi.org/10.1016/j.neuron.2024.01.021.
