Mice have brain cells that are dedicated to storing memories of other mice, according to a new study from MIT neuroscientists. These cells, found in a region of the hippocampus known as the ventral CA1, store "social memories" that help shape the mice's behavior toward each other.
The researchers also showed that they can suppress or stimulate these memories by using a technique known as optogenetics to manipulate the cells that carry these memorytraces, or engrams.
"You can change the perception and the behavior of the test mouse by either inhibiting or activating the ventral CA1 cells," says the senior author and Nobel laurate.
In a well-known study published in 2005, researchers at Caltech identified neurons in the human brain that respond specifically to images of celebrities such as Halle Berry or Brad Pitt, leading them to conclude that the brain has cells devoted to storing memories of people who are familiar.
Many of these cells were found in and around the hippocampus, which is also where the brain stores memories of events, known as episodic memories. The MIT team suspected that in mice, social memories may be stored in the hippocampus' ventral CA1, in part because previous studies have suggested that this region is not involved in storing episodic memories.
The researchers set out to test this hypothesis using optogenetics: By engineering neurons of the ventral CA1 to express light-sensitive proteins, they could artificially activate or inhibit these cells by shining light on them as the mice interacted with each other.
First, the researchers allowed one mouse, known as the "test mouse," to spend time with another mouse for two hours, letting the mice become familiar with each other. Soon after, the test mouse was placed in a cage with the familiar mouse and a new mouse.
Under normal circumstances, mice prefer to interact with mice they haven't seen before. However, when the researchers used light to shut off a circuit that connects the ventral CA1 to another part of the brain called the nucleus accumbens, the test mouse interacted with both of the other mice equally, because its memory of the familiar mouse was blocked.
"The inhibition of ventral CA1 leads to impairment of the social memory," another author says. "They cannot show any preference for the novel mouse. They approach both mice equally."
On the other hand, when the researchers stimulated ventral CA1 cells while the test mouse was interacting with a novel mouse, the test mouse began to treat the novel mouse as if they were already acquainted.
This effect was specific to social interactions: Interfering with the ventral CA1 did not have any effect on the mice's ability to recognize objects or locations that they had previously seen.
When the researchers monitored activity of neurons in the ventral CA1, they found that after a mouse was familiarized with another mouse, a certain population of these neurons began to respond specifically to the familiar mouse.
These patterns could be seen even after the mice appeared to "forget" the once-familiar mice. After about 24 hours of separation, the test mice began to treat their former acquaintances as strangers, but the neurons that had been tuned to the familiar mice still fired, although not as frequently. This suggests that the memories are still being stored even though the test mice no longer appear to remember the mice they once knew.
Furthermore, the researchers were able to "re-awaken" these memories using optogenetics. In one experiment, when the test mouse first interacted with another mouse, the researchers used a light-sensitive protein called channel rhodopsin to tag only the ventral CA1 cells that were turned on by the familiarization treatment. When these neurons were re-activated with light 24 hours later, the memory of the once-familiar mouse returned. The researchers were also able to artificially link the memory of the familiar mouse with a positive or negative emotion.
The MIT researchers are now investigating a possible link between social memory and autism. Some people with autism have a mutation of the receptor for a hormone called oxytocin, which is abundant on the surface of ventral CA1 cells. The lab hopes to uncover whether these mutations might impair social interactions.
Neurons devoted to social memory identified!
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