How do we distinguish threat from security? It is an important question not only in our daily lives, but also for human disorders related to fear of others, such as social anxiety or post-traumatic stress disorder (PTSD). A microscope image, from the lab of Steven A. Siegelbaum, PhD, at Columbia’s Zuckerman Institute, shows a powerful technique that scientists used to help us find an answer.
The scientists were investigating the hippocampus, an area of the brain that plays a key role in memory in humans and mice. Specifically, they focused on the CA2 region, which is important for social memory, the ability to remember other individuals, and the CA1 region, which is important for remembering places.
In this new study, the researchers reveal for the first time that CA1 and CA2 respectively encode places and individuals linked to a threatening experience. The results show that, beyond simply recognizing individuals, CA2 helps record more complex aspects of social memory: in this case, whether another individual is safe or risky. The scientists published their findings Oct. 15 in the journal. Nature Neuroscience.
“It is vital for all species that live in social communities, including mice and humans, to have social memories that can help avoid future experiences with others that could prove harmful, while remaining open to individuals that may be beneficial,” he said. Pegah Kassraian, PhD. , a postdoctoral researcher in Siegelbaum’s lab and lead author of the new study. “Scary memories are important for survival and help keep us safe.”
To investigate where scary social memories originate in the brain, Dr. Kassraian and her colleagues chose individual mice. They could run to a location, encounter another mouse they did not know, and receive a mild shock to their foot (much like a static electricity shock that people might receive after walking on a rug and touching a doorknob). Running in the opposite direction to meet a different stranger was safe. Typically, the mice quickly learned to avoid strangers and places associated with the shocks, and these memories lasted at least 24 hours.
To determine where in the hippocampus these memories were stored, the researchers genetically altered the mice to allow them to selectively suppress the CA1 or CA2 regions. Surprisingly, turning off each region had very different effects. When the scientists silenced CA1, the mice could no longer remember where they were attacked, but they could still remember which stranger was associated with the threat. When CA2 was silenced, the mice remembered where they had received the shock, but became indiscriminately afraid of the two strangers they met.
These new findings reveal that CA2 helps mice remember whether past encounters with other people were threatening or safe. The results are also consistent with previous research detailing how CA1 harbors location cells, which encode locations.
Previous research has implicated CA2 in various neuropsychiatric conditions such as schizophrenia and autism. The new study suggests that further investigating CA2 could help scientists better understand social anxiety, post-traumatic stress disorder, and other conditions that can lead to social isolation.
“It is possible that social withdrawal symptoms are related to the inability to discriminate between who is a threat and who is not,” said Dr. Siegelbaum, who is also a professor and chair of the department of neuroscience at the Vagelos College of Physicians and Surgeons in Columbia. . “Targeting CA2 could be a useful way to diagnose or treat disorders related to fear of others.”
The article, “The CA2 region of the hippocampus discriminates social threat from social security,” was published online at Nature Neuroscience on October 15, 2024.
The full list of authors includes Pegah Kassraian, Shivani K. Bigler, Diana M. Gilly, Neilesh Shrotri, Anastasia Barnett, Heon-Jin Lee, W. Scott Young, and Steven A. Siegelbaum.
The authors report no conflicts of interest.