You know that situation when you run into someone from your past, but it takes a while to register how you know them? I had this experience a couple of weeks ago at the DECODE Summit, an ambitious event hosted by Inscopix that brought together stakeholders across the neuroscience community, from academia, government, non-profits, industry, and pharma to grapple with big questions on translating the circuit basis of disease (search #DECODESummit for live tweets from the event). With so many minds meeting from different sectors, a lot of us were seeing folks we hadn’t seen in quite some time, which meant in addition to thinking about the big questions in neuroscience, our brains were constantly discerning familiar faces during the event. According to exciting new research on social memory in mice, we can thank a very specific circuit in our hippocampus for holding the memory –or engram– of whether someone is familiar or a stranger.
In a tour de force, neuroscientists asked whether and how the hippocampus, a brain area long known to be involved in remembering events, or episodic memory, was also involved in social memory. Previous research, mainly by using lesion methods, gave conflicting results about the role of the hippocampus, and whether all or just part of the hippocampus was involved. Researchers from the lab of Dr. Susumu Tonegawa at RIKEN-MIT tested the role of the hippocampus in social recognition by using optogenetics in mice. They engineered excitatory neurons of the CA1 of the hippocampus to express light-sensitive proteins that gave them the ability to activate or inhibit neurons by shining light on the brain while a mouse interacted with familiar and novel mice.
Usually, a mouse interacts more frequently with other mice that are novel to them. But when researchers Okuyama et al. inhibited select neurons of the ventral CA1, and their axonal projections to a specific target, the nucleus accumbens, they shut down the ability of mice to differentiate familiar and novel mice. With repeated “on-off” testing, they showed the result was robust and reversible, indicating the ventral CA1 cells and their projections to the nucleus accumbens make up a neural circuit signature of familiarity.
To see how these same populations of neurons are activated when mice encounter familiar and novel mice, they employed another viral method to express a calcium indicator in the hippocampus. They performed calcium imaging of neural activity by targeting a probe lens to the ventral hippocampus, and then coupling the Inscopix nVista miniature fluorescence microscope. The microscope allows the mice to freely behave. They found that ventral CA1 neurons responded specifically to familiar mice. Plus, the patterns of activity persisted, even after mice behaved as though they had forgotten a once-familiar mouse. The same effect wasn’t seen for novel or familiar objects, indicating it was specific to a social context.
As if the researchers hadn’t already done plenty to show both a necessary and sufficient role of the ventral CA1 neurons of the hippocampus in processing familiarity, they used optogenetics to “re-awaken” memories in mice that seemed to have forgotten that another mouse was familiar. By using a light-sensitive protein called a channelrhodopsin targeted to ventral CA1 cells, they could re-activate the memory, and even artificially link the memory of the familiar mouse with positive or negative emotions.
This study is truly on the cutting-edge of neuroscience, and delves into an area of critical impact to humans. In future work, the researchers are investigating a possible link between social memory and autism. Specifically, some people with autism carry a mutation in the receptor for the social hormone oxytocin, which happens to be abundantly expressed on the surface of ventral CA1 cells. As stated in MIT News, “Tonegawa’s lab hopes to uncover whether these mutations might impair social interactions.”
Oh, and speaking of social, there’s one more thing I want to mention about social media, and your chance to leverage your social connections to make some cash. We love this image of hippocampal pyramidal neurons that Teruhiro Okuyama shared with Inscopix on Twitter. We want to see more beautiful images and videos of data on social media! Post your videos/images on Twitter/FB/Instagram, and tag Inscopix for the chance to win $500. We’re running the #ShowYourData campaign through November 7th, and plan to announce the winners at SfN. Enter today!
Citation: Okuyama T, et. al. Ventral CA1 neurons store social memory. Science. 2016 DOI: 10.1126/science.aaf7003