HMN 2025: How Mouse neurons identify friends in need and friends indeed

A special set of neurons directs mice’s attention to or away from their peers, depending on the situation. The Kobe University discovery has implications for finding causes for neuropsychiatric conditions such as autism spectrum disorder or schizophrenia.

Social interactions abound with decisions: How much time do we spend with a friend? Do we prioritize time with a friend who looks distressed? Like for all behavior, there are specialized clusters of neurons in the brain that are responsible for fine-tuning such complex behavior, and it is known that developmental defects in these areas are related to neuropsychiatric disorders such as autism spectrum disorder or schizophrenia.

Kobe University neuroscientist Takumi Toru has a long history of research on discovering the neurological basis of these disorders. He says, “We have previously identified in mice a neuron cluster that’s active during social interaction and now we wanted to clarify the role of a specific kind of signal-modulating cell, so-called ‘PV interneurons,’ that we knew are there.”

Using an endoscopic camera with its lens implanted directly into the brain of genetically modified mice, Takumi’s team was able to record in real time which neurons were active during different activities. In addition, they also introduced genetic modifications that allowed them to specifically tune down the activity of the target neurons.

In the journal Cell Reports, the Kobe University neuroscientists, in collaboration with Sato Masaaki of Kyoto Institute of Technology, report that mice whose PV interneurons were inhibited exhibited two interesting behavioral characteristics.

First, they failed to become familiar with their peers. Normal mice spend less time with individuals they already know than with strangers they meet for the first time, but the ones with inhibited PV interneurons would spend just as much time with peers as with strangers. And second, normal mice, when given the choice between two peers, one stressed and one unstressed, would spend more time with the stressed one. The inhibited mice, however, did not exhibit this consolation behavior.

“Our findings are the first to demonstrate that these particular cells act as a switch in the ‘social cell’ network to control empathetic behavior,” explains Takumi.

In a separate experiment, where mice were allowed to freely interact with individuals they met for the first time, inhibited mice did not exhibit any differences from normal ones. This demonstrates that the role of PV interneurons is not so much connected to social behavior in general, but in modulating the preference for social targets and thus in making social choices.

Takumi says, “This finding is an important step toward understanding the neural basis of human sociality. Abnormalities in PV interneurons have been reported in model animals and patient brains with autism spectrum disorder and schizophrenia. In the future, further comparative studies between mice and humans may lead to new treatment strategies.”