NEWLY DISCOVERED BRAIN CELLS EXPLAIN A PROSOCIAL EFFECT OF OXYTOCIN
Oxytocin, the body's
natural love potion, helps couples fall in love, makes mothers bond with their
babies, and encourages teams to work together. Now new research at Rockefeller
University reveals a mechanism by which this prosocial hormone has its effect
on interactions between the sexes, at least in certain situations. The key, it
turns out, is a newly discovered class of brain cells.
"By identifying
a new population of neurons activated by oxytocin, we have uncovered one way
this chemical signal influences interactions between male and female
mice," says Nathaniel Heintz, James and Marilyn Simons Professor and head
of the Laboratory of Molecular Biology.
The findings,
published today in Cell (October 9), had their beginnings in a
search for a new type of interneuron, a specialized neuron that relays messages
to other neurons across relatively short distances. As part of her doctoral
thesis, Miho Nakajima began creating profiles of the genes expressed in
interneurons using a technique known as translating ribosome affinity
purification (TRAP) previously developed by the Heintz lab and Paul Greengard's
Laboratory of Molecular and Cellular Neuroscience at Rockefeller. Within some
profiles from the outer layer of the brain known as the cortex, she saw an
intriguing protein: a receptor that responds to oxytocin.
"This raised
the question: What is this small, scattered population of interneurons doing in
response to this important signal, oxytocin?" Nakajima says. "Because
oxytocin is most involved in social behaviors of females, we decided to focus
our experiments on females."
To determine how
these neurons, dubbed oxytocin receptor interneurons or OxtrINs, affected
behavior when activated by oxytocin, she silenced only this class of
interneurons and, in separate experiments, blocked the receptor's ability to
detect oxytocin in some females. She then gave them a commonly used social
behavior test: Given the choice between exploring a room with a male mouse or a
room with an inanimate object -- in this case a plastic Lego block -- what
would they do? Generally, a female mouse will go for the non-stackable choice.
Legos just aren't that interesting to rodents. But Nakajima's results were
confusing: Sometimes the mice with the silenced OxtrINs showed an abnormally
high interest in the Lego, and sometimes they responded normally.
This led her to
suspect the influence of the female reproductive cycle. In another round of
experiments, she recorded whether the female mice were in estrus, the sexually
receptive phase, or diestrus, a period of sexual inactivity. Estrus, it turned
out, was key. Female mice in this phase showed an unusual lack of interest in
the males when their receptors were inactivated. They mostly just sniffed at
the Lego. There was no effect on mice is diestrus, and there was no effect if
the male love interest was replaced with a female. When Nakajima tried the same
alteration in males, there was also no effect.
"In general,
OxtrINs appear to sit silently when not exposed to oxytocin," says Andreas
Görlich, a postdoc in the lab who recorded the electrical activity of these
neurons with and without the hormone. "The interesting part is that when
exposed to oxytocin these neurons fire more frequently in female mice than they
do in male mice, possibly reflecting the differences that showed up in the
behavioral tests."
"We don't yet
understand how, but we think oxytocin prompts mice in estrus to become
interested in investigating their potential mates," Nakajima says.
"This suggests that the social computation going on in a female mouse's
brain differs depending on the stage of her reproductive cycle."
Oxytocin has similar
effects for humans as for mice, however, it is not yet clear if the hormone influences
the human version of this mouse interaction, or if it works through a similar
population of interneurons. The results do, however, help explain how humans,
mice and other mammals respond to changing social situations, Heintz says.
"Oxytocin
responses have been studied in many parts of the brain, and it is clear that
it, or other hormones like it, can impact behavior in different ways, in
different contexts and in response to different physiological cues," he
says. "In a general sense, this new research helps explain why social
behavior depends on context as well as physiology."
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