When Activated, ‘Social’ Brain Circuits Inhibit Feeding Behavior In Mice

When Activated, ‘Social’ Brain Circuits Inhibit Feeding Behavior In Mice

Researchers at Stanford demonstrated that direct stimulation of fewer than two dozen neurons linked to social interaction was enough to suppress a mouse’s drive to feed itself.

Feeding behavior and social stimulation activate intermingled but distinct brain circuits, and activating one circuit can inhibit the other, according to a new study by researchers at Stanford University.

The researchers demonstrated in mice that direct stimulation of fewer than two dozen nerve cells, or neurons, linked to social interaction was enough to suppress the animals’ drive to feed themselves — a finding with potential clinical significance for understanding and treating eating disorders such as anorexia.

The researchers made these findings by developing a technique for teasing apart separate but closely intertwined sets of neurons in the brain.

A paper detailing the findings and the method used to obtain them was published online Jan. 16 in Nature . The senior author is Karl Deisseroth, MD, PhD, the D.H. Chen Professor and professor of bioengineering and of psychiatry and behavioral sciences and a Howard Hughes Medical Instituteinvestigator. Lead authorship is shared by postdoctoral scholars Joshua Jennings, PhD, and Christina Kim, PhD, along with staff scientist James Marshel, PhD.

Social curbs on eating behavior

“We know social situations can inhibit the urge to eat,” Deisseroth said. “One example is the behavior of people at different levels of dominance in a social hierarchy. You’re not going to dive into that plate of ribs when you’re dining in the presence of royalty.”

Anorexia is another example. “People with anorexia report that a powerful driver, at the disorder’s onset, was feedback from others indicating they’d be rewarded for restricting their food intake,” said Deisseroth.

Virtually nothing is known about the neural underpinnings of this inhibition, he said. “We sought to understand, at the level of individual neurons, how these potentially competing drives may negotiate with each other, and how the brain circuits associated with feeding versus social behavior may interact.”

Deisseroth’s group focused on a part of the brain called the orbitofrontal cortex, a sheet of cells that, in both mice and humans, lies on the brain’s outer surface toward the front of the organ. This brain region, which is similar in the two species, has been shown in human imaging studies to be active when subjects are wishing for, seeking, obtaining and consuming food, or when they’re socially engaged.

Exploring the interactions of feeding and social drives was guaranteed to be tricky.

“It’s not as if there is a cluster of ‘feeding’ neurons’ and another cluster of ‘social’ neurons sitting in two neatly labeled clumps in the orbitofrontal cortex, so you can just position an electrode in one or the other cluster and find out all you need to know,” Deisseroth said. The neurons driving and responding to these different activities are interspersed, scarce and scattered throughout the orbitofrontal cortex like sprinkles on a cupcake. Plus, they all look pretty much the same.

So the researchers designed a sophisticated system for simultaneously stimulating and monitoring activity in multiple designated neurons. This let them determine which orbitofrontal-cortex neurons were active during feeding-associated or social activities, or both, or neither. The technology also allowed them to stimulate on the order of 20 neurons identified as dedicated to one or the other activity and watch what behavior resulted.

Over the past decade and a half, Deisseroth has pioneered the development of an experimental approach called optogenetics, in which a gene for a light-sensitive protein called an opsin is inserted into neurons so they can be activated by pulses of laser light reaching them via an implanted optical fiber. Recent advances in his lab have optimized one such opsin to the point where his team can stimulate numerous selected, behaviorally categorized neurons at a time in a mammal.

“This study builds on our initial demonstration in mammals of single cell control with optogenetics in 2012, but now marks the first demonstration of control of mammalian behavior by the manipulation of multiple, individually specified neurons,” he said.