Suspect List Shortens For Maternal Aggression's Brain Origins

The findings will be presented by Johns Hopkins University postdoctoral researcher Stephen Gammie at this week's annual meeting of the Society for Neuroscience in New Orleans. Gammie says the results are an important step towards pinning down the origins of this type of aggressive behavior in the mouse brain, an accomplishment that could help scientists better probe aggression's origins in humans. To prevent strange male mice from harming their offspring, female mice with pups normally attack any such mouse who comes into their area. A few mouse moms, however, fail to show this response. Gammie divided mice into groups based on this distinction, compared the two groups for presence of compounds related to brain activity, and was able to identify four brain areas that were active in the aggressive moms but not in the non-aggressives.

Given the mouse brain's small size, cutting down the list of suspects for production of aggression might seem an unlikely or unimportant step. But even the humble mouse brain has sufficient structural and biochemical complexity to resist giving up its secrets easily, Gammie says.

"By taking advantage of natural variation in aggression, our study decreased the odds of confusing aggression control mechanisms with other areas of the brain activated when a strange male mouse approaches," says Gammie. "For example, areas of the brain that are involved in seeing and smelling the males become active in both groups of mouse moms. Areas that become active only in the aggressive moms have a good chance of being linked to production of the primary difference in behavior, the aggression."

Gammie's postdoctoral mentor, Hopkins psychology and neuroscience professor Randy Nelson, was one of a group of several Hopkins scientists who discovered a link five years ago between the brain neurotransmitter nitric oxide and aggression in male mice. In an attempt to greatly reduce or eliminate nitric oxide in the mice's brains, scientists had given them a defective copy of a gene involved in nitric oxide production. They found that this led to a dramatic increase in aggression levels among the male mice.

Working with Nelson, Gammie showed last year that the genetic change had the opposite effect on females, decreasing their aggression when they were exposed to strange males after giving birth.

In the new experiments, funded by the National Institutes of Health and the National Institute of Mental Health, Gammie and Nelson exposed normal, non-altered mouse moms to strange males and tested their brains for transcription factors known as pCREB and cFOS. Both pCREB and cFOS have been linked to nerve cell activity by other labs. Some of the regions highlighted in the new experiment have shown up before in experiments by Gammie and other researchers.

For example, the paraventricular nucleus has been linked to aggression in related research into the behavior of prairie voles. Voles are also rodents and look like a stout mouse or rat, but are more closely related to lemmings and muskrats than to mice. The paraventricular nucleus is located in the hypothalamus, a brain area where environmental stimuli are integrated with internal signals from the brain, and a response to the stimuli begins to be produced. "We're not there yet, but the pieces of the puzzle are starting to come together," Gammie says. With a list of likely suspects based on the research of Gammie and others, neuroscientists can begin to consider more precise pharmacological manipulation of the brain to zero in on the brain circuitry that produces aggression.

"Maternal aggression occurs in almost all mammals. It is a highly adaptive behavior because it helps keep offspring alive," Gammie says, noting that highly adaptive characteristics tend to be preserved by evolution. "If we gain a detailed understanding of the neural circuitry underlying maternal aggression in rodents, then it may be possible later on to use that information to help understand how maternal aggression is controlled in humans."