AUTISM NEURONS CONTROLLING SOCIAL BEHAVIOR FOUND

Humans  with autism often show a reduced frequency of social interactions and an increased tendency to engage in repetitive solitary behaviors. Autism has also been linked to dysfunction of the amygdala, a brain structure involved in processing emotions. Now Caltech researchers have discovered antagonistic neuron populations in the mouse amygdala that control whether the animal engages in social behaviors or asocial repetitive self-grooming. This discovery may have implications for understanding neural circuit dysfunctions that underlie autism in humans

This discovery, which is like a "seesaw circuit," was led by postdoctoral scholar Weizhe Hong in the laboratory of David J. Anderson, the Seymour Benzer Professor of Biology at Caltech and an investigator with the Howard Hughes Medical Institute. The work was published online on September 11 in the journalCell.

"We know that there is some hierarchy of behaviors, and they interact with each other because the animal can't exhibit both social and asocial behaviors at the same time. In this study, we wanted to figure out how the brain does that," Anderson says.

Anderson and his colleagues discovered two intermingled but distinct populations of neurons in the amygdala, a part of the brain that is involved in innate social behaviors. One population promotes social behaviors, such as mating, fighting, or social grooming, while the other population controls repetitive self-grooming -- an asocial behavior.

Interestingly, these two populations are distinguished according to the most fundamental subdivision of neuron subtypes in the brain: the "social neurons" are inhibitory neurons (which release the neurotransmitter GABA, or gamma-aminobutyric acid), while the "self-grooming neurons" are excitatory neurons (which release the neurotransmitter glutamate, an amino acid).

To study the relationship between these two cell types and their associated behaviors, the researchers used a technique called optogenetics. In optogenetics, neurons are genetically altered so that they express light-sensitive proteins from microbial organisms. Then, by shining a light on these modified neurons via a tiny fiber optic cable inserted into the brain, researchers can control the activity of the cells as well as their associated behaviors.

Using this optogenetic approach, Anderson's team was able to selectively switch on the neurons associated with social behaviors and those linked with asocial behaviors.

With the social neurons, the behavior that was elicited depended upon the intensity of the light signal. That is, when high-intensity light was used, the mice became aggressive in the presence of an intruder mouse. When lower-intensity light was used, the mice no longer attacked, although they were still socially engaged with the intruder -- either initiating mating behavior or attempting to engage in social grooming.

When the neurons associated with asocial behavior were turned on, the mouse began self-grooming behaviors such as paw licking and face grooming while completely ignoring all intruders. The self-grooming behavior was repetitive and lasted for minutes even after the light was turned off.

The researchers could also use the light-activated neurons to stop the mice from engaging in particular behaviors. For example, if a lone mouse began spontaneously self-grooming, the researchers could halt this behavior through the optogenetic activation of the social neurons. Once the light was turned off and the activation stopped, the mouse would return to its self-grooming behavior.

Surprisingly, these two groups of neurons appear to interfere with each other's function: the activation of social neurons inhibits self-grooming behavior, while the activation of self-grooming neurons inhibits social behavior. Thus these two groups of neurons seem to function like a seesaw, one that controls whether mice interact with others or instead focus on themselves. It was completely unexpected that the two groups of neurons could be distinguished by whether they were excitatory or inhibitory. "If there was ever an experiment that 'carves nature at its joints,'" says Anderson, "this is it."

This seesaw circuit, Anderson and his colleagues say, may have some relevance to human behavioral disorders such as autism.

"In autism," Anderson says, "there is a decrease in social interactions, and there is often an increase in repetitive, sometimes asocial or self-oriented, behaviors" -- a phenomenon known as perseveration. "Here, by stimulating a particular set of neurons, we are both inhibiting social interactions and promoting these perseverative, persistent behaviors."

Studies from other laboratories have shown that disruptions in genes implicated in autism show a similar decrease in social interaction and increase in repetitive self-grooming behavior in mice, Anderson says. However, the current study helps to provide a needed link between gene activity, brain activity, and social behaviors, "and if you don't understand the circuitry, you are never going to understand how the gene mutation affects the behavior." Going forward, he says, such a complete understanding will be necessary for the development of future therapies.

But could this concept ever actually be used to modify a human behavior?

"All of this is very far away, but if you found the right population of neurons, it might be possible to override the genetic component of a behavioral disorder like autism, by just changing the activity of the circuits -- tipping the balance of the see-saw in the other direction," he says.

CHILDS POOR DECISION MAKING SKILLS CAN PREDICT LATER BEHAVIOR PROBLEMS

Children who show poor decision-making skills at age 10 or 11 may be more likely to experience interpersonal and behavioral difficulties that have the potential to lead to high-risk health behavior in their teen years, according to a new study from Oregon State University psychology professor.

These findings suggest that less-refined decision skills early in life could potentially be a harbinger for problem behavior in the future," said Joshua Weller, an assistant professor in the School of Psychological Science in OSU's College of Liberal Arts.

However, if poor decision-making patterns can be identified while children are still young, parents, educators and health professionals may have an opportunity to intervene and help those children enhance these skills, said Weller, who studies individual differences in decision-making.

"This research underscores that decision-making is a skill and it can be taught," he said. "The earlier you teach these skills, the potential for improving outcomes increases."

His findings were published recently in the Journal of Behavioral Decision Making. Co-authors are Maxwell Moholy of Idaho State University and Elaine Bossard and Irwin P. Levin of the University of Iowa. The research was supported by a grant from the National Science Foundation.

The researchers wanted to better understand how pre-adolescent children's decision-making skills predicted later behavior. To do so, they conducted follow-up assessments with children who had participated in a previous decision-making study.

About 100 children, ages 10 and 11, participated in the original study, where they answered questions that helped assess their decision-making skills. They were evaluated based on how they perceived the risks of a decision, their ability to use appropriate decision-making rules and whether their confidence about a decision matched their actual knowledge on a subject.

For the new study, researchers invited the original study participants -- now 12 and 13 years old -- and their parents back for a follow-up. In all, 76 children ages participated in the second study, which included a behavior assessment that was completed by both the parent and the child.

The behavior assessment included questions about emotional difficulties, conduct issues such as fighting or lying and problems with peers. Those kinds of behavioral issues are often linked to risky health behavior for teens, including substance abuse or high-risk sexual activity, Weller said.

Researchers compared each child's scores from the initial decision-making assessment to the child's and their parent's behavioral reports. They found that children who scored worse on the initial decision-making assessment were more likely to have behavioral problems two years later.

"Previous studies of decision-making were retrospective," Weller said. "To our knowledge, this is the first research to suggest how decision-making competence is associated with future outcomes."

The research provides new understanding about the possible links between decision-making and high-risk behavior, Weller said. It also underscores the value of teaching decision-making and related skills such as goal-setting to youths. Some interventions have demonstrated promise in helping children learn to make better decisions, he said.

In another recent study, Weller and colleagues studied the decision-making tendencies of at-risk adolescent girls who had participated in an intervention program designed to reduce substance abuse and other risky behavior. The program emphasized self-regulation, goal-setting and anger management.

The study found that girls who received the intervention in fifth-grade demonstrated better decision-making skills when they were in high school than their at-risk peers who did not participate in the intervention program.

"Most people can benefit from decision-making training. Will it always lead to the outcome you wanted? No," Weller said. "However, it boils down to the quality of your decision-making process."

That is something that parents and other adults can help children learn. For instance, a parent can talk about difficult decisions with a child. By exploring multiple points of view or showing other people's perspectives on the issue, the child learns to consider different perspectives, he said.

"Following a good process when making decisions can lead to more favorable outcomes over time," Weller said. "Focus on the quality of the decision process, rather than the outcome."