An emotional mechanism at the heart of most of our social behaviors, empathy is our ability to take into account the suffering of others. Associated for several years with the insular cortex, a brain region located at the heart of the two lobes of our brain, its biological functioning remains nonetheless mysterious. Among the many gray areas of the subject: the role of the neural regulatory systems of this region of the brain; a question that a team of Japanese researchers from Kobe University has been investigating as part ofa new study published in the newspaper Cell Reports.
“The insular cortex is a particularly interesting area because it is responsible for integrating a wide variety of emotions and sensations, explains Professor Toru Takumi, neurobiologist and first author of the study interviewed by Science and Future. Clinically, its dysfunction has been implicated in many neuropsychiatric disorders such as autism.”
Parvalbumin interneurons, builders of familiarity
The core target of this study is the interneurons parvalbumin: a specific category of inhibitory neurons capable of creating multiple connections and distinguished by their ability to secrete parvalbumin, a protein involved in ion transport. Present throughout the brain, those located in the insular cortex seem more directly linked to social behaviors: a theory that seems to be confirmed by the Kobe team's experiments.
To better understand their role, the Japanese study, as in any self-respecting study, inhibited the interneurons to identify the mechanisms that would stop functioning in their absence. Once the receptors of their parvalbumin interneurons were blocked, preventing any possibility of activating them during social interactions, the test mice then underwent various tests to assess their level of empathy. Highly gregarious, the social behaviors of mice are indeed well known to researchers, and while the level of sociability of the inhibited mice does not seem to change—no dark and misanthropic mice to report—their behaviors do, however, present a number of anomalies.
During the first test, a simple repeated contact with an unknown mouse, the uninhibited mice should, for example, spend less and less time with their new congener and go explore their environment once the other mouse has become familiar. This behavior is completely absent from the inhibited mice, which will always seem to “discover” their companion, regardless of the number of interactions.
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At the neuronal level, this results in the recruitment of so-called "social" neurons, which are only activated when the mouse is about to play with a new conspecific. In normal mice, this number tends to decrease from one session to the next, but also to involve different neurons from one interaction to the next, with very few neurons common to each occurrence. In inhibited mice, however, this number varies much less, as if the encounter was always the first.
A reaction that can be explained by the already proven role of parvalbumin interneurons in the reorganization of neurons and the creation of the feeling of familiarity. “The inhibited mouse might not even remember it.”, Professor Takumi theorizes cautiously.
Understanding the pain of others
But if recognizing others is an essential part of social relationships, what about empathy? Inhibited mice do indeed approach their peers, but do they really care about them? And how can this be proven?
To answer these questions, especially the last one, knowledge of the behavior of laboratory mice comes into play again: when placed in the presence of a fellow mouse showing signs of stress, characterized by a lack of activity in the stressed subject, the mice will naturally interact with them to try to console them. A behavior that is reminiscent of that of laboratory rats, who, when faced with a companion locked in a cage, will prefer to free it rather than eat.
But what about inhibited mice? When placed in the presence of a mouse stressed by a previous test, the latter will indeed go to see them... but spend much less time with it than a control mouse. Similarly, when placed in the presence of mice presenting different levels of stress - obtained through a 1 or 3 minute swim - the inhibited mice do not seem to show any distinction between their congeners, while a control mouse would spend significantly more time with the mouse that moves the least. Result: while the inhibited mice do indeed display social behaviors, their differentiation of the emotions of their congeners seems reduced.
These results suggest an important role for parvalbumin interneurons in creating feelings of familiarity, but also in recognizing the emotions of others; one of the most important components of empathy.
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