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Vol. LXV, No. 20
September 27, 2013
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Bargmann’s Roundworm Studies Yield Insights About Brain Circuitry

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Dr. Cori Bargmann kicks off the 2013-2014 Wednesday Afternoon Lecture Series on Sept. 9.

Dr. Cori Bargmann kicks off the 2013-2014 Wednesday Afternoon Lecture Series on Sept. 9.

Although the much-studied roundworm is about 5,000 genes short of the human total—the official score is around 25,000 for us and 20,000 for them—neuroscientists such as Dr. Cori Bargmann, who is co-leading the working group that is defining the goals of the recently announced NIH BRAIN Initiative, have been able to map out basic neural circuits that we likely share with Caenorhabditis elegans.

At a special Monday kickoff of the 2013-2014 Wednesday Afternoon Lecture Series on Sept. 9, Bargmann shared painstaking investigations of roundworm behavior—they dwell, they roam, they twist and turn (but they write neither country tunes nor, as Bargmann noted, Shakespeare)—that has been linked to the activation of specific neural circuits.

In his introduction to Bargmann’s talk, NIH director Dr. Francis Collins expressed gratitude for her support of a brain-mapping effort due to begin in FY 2014: “We are particularly grateful to Cori for putting her lab work on hold for the last 3 months” so she could co-lead the BRAIN Initiative working group and help determine its scientific goals. “Next summer, we hope to announce a 5-year plan for the initiative. It is a very exciting time in neuroscience.”

Continued...

The excitement is founded on reasoning that Bargmann, a professor at Rockefeller University, made explicit for a Masur Auditorium audience: break a problem down to its simplest elements in an effort to discover the biological basis of behavior.

Animals are always learning and exploring, and display a range of different behaviors, Bargmann explained, but “there are common themes, even when the outward manifestations appear different.”

For example, there appear to be underlying rules, across species, regulating when and how mating and courtship behavior is expressed. Once a bundle of joy emerges, there are additional rules—based on biology and expressed at a molecular level—that govern caring for offspring.

“Like all neurobiologists, I would like to understand the human brain,” Bargmann quipped, “particularly my husband’s.”

“Like all neurobiologists, I would like to understand the human brain,” Bargmann quipped, “particularly my husband’s.”

Photos: Bill Branson

It just so happens that the first mammalian neuropeptides ever discovered and purified—oxytocin and vasopressin—are crucial to such basic behaviors. Bargmann went so far as to call oxytocin the “one-stop shopping of mammalian behavior at birth.” It turns out that C. elegans has a molecule like oxytocin, which investigators have dubbed nematocin (nematode oxytocin).

But you don’t get to the warmth and nurturing associated with oxytocin without a related peptide linked to mating and aggression—vasopressin, the “She’s mine—beat it!” (or, alternately, the “You Ain’t Woman Enough to Take My Man”) neuropeptide.

In an effort to understand how neuropeptides regulate mating behavior, scientists have conducted experiments showing, Bargmann said, that both oxytocin and vasopressin are “elements of all aspects of mating behavior.” This happened “very early on in animal evolution,” she said, and extends across the animal kingdom, all the way to man.

“Like all neurobiologists, I would like to understand the human brain,” Bargmann quipped, “particularly my husband’s.”

Bargmann is convinced that, with the complete neural wiring diagram of C. elegans already in hand, science is primed for an ascent of that Everest of biology, the human brain, with its 10 billion neurons and 10 trillion synapses. “Worm studies will help us along the path to the brain,” she said.

Her own recent focus has been on roundworm foraging behavior as a lens through which one can learn about the structure of neuromodulatory circuits. Like a federal worker along about noontime, worms have bouts of high activity and exploration as they roam around seeking nourishment. This is punctuated with periods of rest or quiet wakefulness once sated.

Neuroscientists have discovered that two important molecules drive these states: serotonin, which promotes “dwelling,” and PDF (pigment dispersing factor), a sort of reciprocal to serotonin that makes a critter restless.

Bargmann and a team of investigators that she credits as the real reason she has won such recent scientific honors as the 2013 Breakthrough Award in Life Sciences and the 2012 Kavli Prize in Neuroscience (“My success in science has been due to my good taste in people,” she said), are meticulously linking specific molecules to specific behaviors, discerning elemental circuitry and discovering important new neuromodulators.

“We’re never going to teach the worm to play the piano or speak French,” she allowed, but C. elegans will serve as an essential base camp on the way to the summit of the human brain.

Bargmann’s entire talk, “Neuromodulatory Circuits and Motivated Behavior,” may be viewed at http://videocast.nih.gov/summary.asp?Live=13153.


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