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June 20, 2013
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Sex in the Brain


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In the Beginning Was the Worm

Worm Atlas



   10.25.07
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By turning on a gene in the brain, scientists have shown they can reverse sexual orientation in worms. As this ScienCentral News video explains, they did it to prove they could gain control of an organism's brain circuitry.


The Worms Turn

Microscopic nematode worms are among the most-studied organisms in biology and genetics-- revealing the role of genes in addiction, obesity, and even longevity. Now researchers at the University of Utah have demonstrated they can make them behave like the opposite sex by activating a gene in their brains.

"A female avoids other females and males are attracted to females. And so what we can do is swap those behaviors," says Howard Hughes Medical Institute investigator Erik Jorgensen. "But what's really important is that we can identify the circuits in the brain that underlie that behavior. So we have a group of cells that we can now manipulate and demonstrate how this whole process works-- how does the brain work."





Worms Pointed Out
C. elegans is pointed out on monitor
While the worm, C. elegans, only has 302 nerve cells, "The nerve cell in a worm is exactly how a nerve cell in the human brain works," Jorgensen says. "So if we can understand it in a worm we'll be able to understand how the brain works in the human and that is our goal."

As Jorgensen, Jamie White and their colleagues wrote in the journal, Current Biology, the study showed that in worms, sexuality is hard-wired in the brain and is not affected by the body or hormones.

"So that means that we can now study the brain and the brain alone and understand how this behavior arises," says Jorgensen. He says that's not true in people, where hormones as well as thinking and consciousness play a role.






Worm Tracks

In a series of elegant experiments, the researchers first had to identify which nerve cells were responsible for the behavior. "We took a jellyfish protein and expressed it in these cells, so now we could see that cell in the brain, and using a laser we can then perform microsurgery and kill that cell and basically eliminate that part of the circuit and then test those animals," he explains. "And we can ask whether those males are still attracted to females. If they weren't, we knew we had identified the correct cells."

The test for attraction, or lack thereof? Simple -- wash some female worms. The females' odors, or pheromones, end up in the wash solution, which they put onto a spot on a petri dish coated with agar. The worms' tracks in the agar record whether they head towards the odor spot or away from it.

Surprisingly, even though male nematodes have some nerve cells that differ from females, White could kill those cells and still get males that were attracted to females. "That tells us that the cells in the brain that are shared by males and females [are] responsible for sexual behaviors," Jorgensen says.

Worms on Monitor
Closer image of C. elegans worms
They then performed the genetics switching to prove they could control these cells.
Jorgensen says their discoveries don't address whether there's any natural variation in sexual orientation in worms, because they use worms bred in the lab, not the wild.




"Whether differences in this gene activity could control diversity in worms is not something that we see in our experiments," Jorgensen says. "We're not taking a population of worms you would see in nature. We're taking animals that have been bred to be the same, and this behavior is robust and reliable. So it's possible that there is diversity in nature. We wouldn't see it in the lab."


Genes, Brains and Behaviors

Jorgensen says their findings are consistent with findings in flies and other animals that there are groups of brain cells that are dedicated to sexual behaviors.

But he says that finding out that sexual attraction in worms is hard-wired into the brain doesn't tell anything about human sexual orientation -- or any other human behaviors.

"I think that these, what we consider complicated behaviors, sexual attraction, are wired into that brain, so that worms really are hard-wired," he says. "Are humans hard-wired? Are we simply the output of our genes? That's not true-- our brains are much larger, there are phenomena that arise from having such a complicated brain, such as will and consciousness, and we don't understand those things. And it's going to be hundreds of years, I think, before we finally understand these emergent properties of the human brain."

But to ever understand human brains and behaviors, the researchers say the place to start is the wiring of a brain circuit in a tiny worm.

Even though they are primitive compared to humans, nematode worms have most of the same genes as we do. But unlike with humans, scientists possess the complete wiring diagram of these worms' brains.

"Just open up the book and it has this cell is connected to this cell, and so we know exactly how all of the components are connected, and we can begin to figure out how that wiring diagram works, how does a circuit of the brain work," Jorgensen says.

This research was published in Current Biology online ahead of print, October 25, 2007 and funded by the National Science Foundation.


 
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