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.
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