Why do some people appear to be natural parents, while others smother their children, ignore them altogether or become outright abusive?
Part of the answer, Catherine Dulac believes, may be found in the brains of mice.
The Higgins Professor of Molecular and Cellular Biology and a Howard Hughes Medical Institute investigator, Dulac and a team of scientists described, for the first time, how separate pools of neurons control individual aspects of parenting behavior in mice. The work is described in an April 11 paper published in Nature.
"Any social behavior - whether it's fighting or mating or parenting - it's not one thing, it's multiple things," Dulac said. "What's fascinating is no one had ever determined how social behaviors are controlled. With this particular example of parenting, we showed that each discrete step is controlled by a different set of neural projections.
"Because this complex behavior is built from smaller parts, each of those pools can be regulated differently," Dulac added. "So you can imagine circumstances where those parts may be working better or worse, leading to differences in parenting."
The new study, Dulac said, grew out of her 2014 discovery that galanin neurons in the brain's medial preoptic area (MPOA) were responsible for regulating parental behavior.
When activated, the earlier study found, sexually inexperienced male mice - who would normally attack pups - instead began grooming them. Conversely, when researchers turned the neurons off in virgin females, they ignored pups rather than grooming them.
Using that information as a starting point, Dulac and her team used genetic tools to understand precisely how those galanin neurons control the various aspects of parenting behavior by tracing which brain areas send signals to the neurons.
"What we found is these neurons get information from all over the brain," Dulac said. "But we also found they send projections to multiple brain areas, including four that each appear to regulate a particular aspect of parenting behavior."
One projection, Dulac said, stimulates the brain region responsible for controlling the motor aspects of parenting - sniffing and grooming of pups, retrieving pups to the nest and more.
"If we activate this particular set of projections in an animal that is not a parent, they begin to act like a parent - they retrieve the pups and groom them," she said. "And if we inhibit them in animals which are parents, there's no longer any parenting behavior."
A second set of projections, researchers found, had no effect on motor behavior, but instead controlled the motivation of mice to interact with pups.
"If you put a barrier between an animal and the pups, stimulating that particular projection will enhance their desire to get across the barrier to the pups," Dulac said.
That region, however, controls only the mouse's desire to reach the pups, Dulac said, not motor behaviors like grooming, so while exciting the neurons will make mice work furiously to reach pups, once there, they largely ignore them.
The third area, Dulac said, alters the way mice with pups react to other mice - when activated mice are less likely to interact with intruders, while lower activation causes mice to ignore pups in favor of interacting with other mice. The fourth area, meanwhile, is responsible for hormone changes that appear in parent mice.
Perhaps most importantly, Dulac said, because each of those projections are controlled by separate pools of galanin neurons, each can be individually regulated, leading to a wide varitety of parenting behaviors.
"This particular configuration or architecture is very similar to what has been found in the spinal column for the control of motor behaviors," Dulac said. "When you walk or you run, different muscles are engaged, and each does something different. In the motor system, each muscle is controlled by a different pool of motor neurons. What we found here is a where each component of a social behavior is also controlled by different pools of neurons."
Going forward, Dulac said, she hopes to explore ways to manipulate each of those projections to understand exactly what their roles are in controlling behavior, and whether similar systems of neurons are preserved in humans.
"Every time people have identified a population of neurons doing something in the hypothalamus it's preserved across all vertebrates," Dulac said. "The neurons involved in reproduction, they're found in everything from fish to humans. The same for areas involved in everything from stress to sleep to feeding behavior.
"I would bet the same neurons are going to be found in the human brain doing the same thing," she continued. "And they may potentially be effected by disorders of one sort or another."
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This research was supported with funding from Human Frontier Long-Term Fellowship, an EMBO Long-Term Fellowship, a Sir Henry Wellcome Fellowship, the Fondation pour la Recherche Médicale, a NIH K99 Award, a NARSAD Young Investigator Award, a Howard Hughes Gilliam Fellowship, a Harvard Mind Brain and Behavior faculty grant, the NIH and the Howard Hughes Medical Institute.
Journal
Nature