Home Dog senses Amylin peptide in the brain detects isolation and drives social contact-seeking behavior

Amylin peptide in the brain detects isolation and drives social contact-seeking behavior

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As we have experienced during the COVID pandemic, loneliness or perceived social isolation is a major stressor for social animals and increases the risk of various mental and physical health issues such as depression, substance abuse, obesity and premature death. In an effort to understand the neural basis of loneliness, Kansai Fukumitsu and others at the RIKEN Center for Brain Science (CBS) in Japan found a molecular indicator and regulator of social isolation in female mice. The new study, published in Nature Communicationreports that social contact-seeking behavior in mice is driven by the peptide amylin in the medial preoptic area (MPOA) of the forebrain, and that being alone decreases the amount of amylin in this region of the brain.

Previous research by the RIKEN CBS group led by Kumi Kuroda has shown that in mammals, the desire for maternal care also stems from the MPOA. Specifically, amylin-responsive neurons in the central MPOA (cMPOA) are required for maternal motivation. As is often the case in scientific discovery, the original link between amylin and loneliness was unintentional. “Studying amylin signaling in maternal care, we noticed that the amount of amylin in cMPOA was dependent on the housing conditions of the mice,” Kuroda explains.

This observation led to the new study which examined behavioral and neural responses to social isolation and social gathering in female mice. The researchers found that six days of isolation resulted in an almost complete disappearance of amylin, which returned to normal two weeks after the mice were reunited with their cagemates. This was true even when mice were separated from cagemates by a windowed divider in the same cage, indicating that female mice needed to establish free physical contact with other mice to maintain amylin expression in cMPOA. . Next, the researchers carefully ruled out the possibility that amylin levels were regulated by other factors such as boredom, general stress, physical contact with humans, or contact with other mice for defensive purposes. . They also found that amylin-expressing neurons in cMPOA are turned off when isolating and turned on when reuniting.

When the female mice were separated from their cagemates by the window separator, they first vigorously bit the bars of the separator. This biting behavior was only observed when other mice were on the other side of the divider, and so the mice appeared to be trying to break the window and reunite with the other mice. This contact-seeking behavior was augmented by specifically activating amylin-expressing neurons using chemogenetics, a biotechnology that allows artificial control of neuronal activity. In contrast, contact-seeking behavior decreased after knocking down amylin in cMPOA. “Of the other molecules reported, amylin is the most responsive to isolation and reunion, and itself facilitates contact-seeking behaviors,” says Kuroda. “With all of these results, we have become convinced that amylin is the main brain player needed for social contact detection and tracing.”

Since the time of Darwin, scientists have postulated that social affiliation in adults stems primarily from parental care. This study provides molecular evidence that supports this notion. “Parental care and female-female social contact are dependent on amylin and increase its expression,” Kuroda says, “This synergy could facilitate cooperative parenting, in which multiple females care for young together, as observed in mice and humans.

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