Pediatricians and parents — and, really, anyone who works with children — have long known that a child’s social needs evolve with age. Yale researchers have now discovered the neurological signaling that marks this process.
In experiments with mice, researchers observed that Agrp neurons, a type of cell in the brain’s hypothalamus region, play a key role in controlling social behavior in young animals but not in adults. The neurons — which regulate primary survival needs like hunger and maintaining body temperature — drive social needs during youth but slowly lose this role in adulthood.
The findings illustrate the importance of social interaction in developing mammals. They also shed new light on how this need is biologically regulated and why it changes as we age and may help scientists better understand developmental social disorders in humans.
The study was published in the journal Current Biology.
“This is the first time you have a neurobiological finding that shows something we already know from experience, and psychologists know from observation,” said Marcelo Dietrich, a professor of comparative medicine and of neuroscience at the Yale School of Medicine, and a faculty member at the Yale Wu Tsai Institute, one of the study’s authors.
Marcelo Dietrich
“While sociability is definitely a primary need of developing mammals, it isn’t a static need,” Dietrich explained. “Childhood sociability focused on caregivers turns into intense adolescent, peer-to-peer sociability that then transitions into more adult social behaviors. We can now see these changing needs in the neuron activity.”
In addition to Dietrich, the authors included researchers from the Yale School of Medicine’s departments of comparative medicine and neuroscience, and from the Yale Center for Molecular and Systems Metabolism.
In their work, researchers measured Agrp activity in mice at different ages, from weanlings through adulthood. Specifically, they sought to observe how Agrp activity would be affected by social connection with others, and if the correlation changed over a lifecycle.
In a series of experiments, the researchers measured Agrp activity after socially isolating mice and then after reuniting them with other mice. They used methods like calcium imaging, which tracks calcium ions to understand neural signaling and communication; and optogenetics, which uses light to influence neuron activity.
They found that social isolation strongly activates Agrp neurons in juveniles, and that social reunions bring their activity back to low levels. But when researchers silenced the Agrp neuron activity in young, isolated mice, the mice were less social overall. Reactivating the neurons renewed their social impulses.
In adult mice, however, none of the Agrp manipulations had any effect, leading researchers to conclude that while these neurons help regulate the drive for social contact during development, the effect stops in adulthood.
“Adults still have social needs, but they’re of a different type,” Dietrich said. “They’re not signaled to Agrp neurons. There are other neurons in the brain, other circuits, that take care of the adult needs.”
The researchers were surprised to find that Agrp signals don’t just stop in childhood, however, but in late adolescence.
“This tells us that these social signals are critical to an animal’s healthy development,” Dietrich said. “You have an attachment to caretakers in your early life, and then during adolescence you transition more to peers, so it’s important to build peer relationships. These characteristics are unique to mammals and present in almost all mammals that we know.”
Agrp neurons also exist in the brains of reptiles, amphibians, and fish, where they regulate messaging related to survival issues, such as hunger, as they do in mammals. “But in mammalian evolution there was a need for connection with caretakers and peers in the juveniles,” Dietrich said.
In 2019, Dietrich’s team published a paper showing that this “need” wasn’t all about satisfying hunger, either. Juveniles also craved connection and comfort from their caregivers. At the time, the researchers found that the neurons were activated when baby mice were separated from their mothers.
“But we found that being away from the mother is what activates these neurons — not missing the mother’s milk,” Dietrich said. “When we separated the babies from the mother and kept giving the milk, the neurons still got activated. Our new research goes deeper into just how critical these social needs really are.”
