Neuroscience Sunday

am2009_logo4:00 PM – What Makes a Man, Mr. Lebowski?

Sex differences appeared to be the unintentional theme of the day, as the press conference I sat in on focused on biology and behavior specific to males. This is an interesting scientific double-reverse – as Arthur Arnold had said earlier in his special lecture, most of neuroscience (and science in general) has experimented on males, which has created occasional problems in applying those results to females. For at least the past decade, that imbalance has been remedied, with most animal studies including both male and female subjects. But that doesn’t meant that aren’t interesting questions remaining about the male brain, and this conference brought together Arnold and four researchers working in that sub-field.

Despite the message of Arnold’s talk earlier (“sex difference is more than just hormones”), the research largely focused on how testosterone – the hormone produced by the male testes – affects behavior. Two of the studies (both from the University of Wisconsin) utilized an interesting animal model, California mice, whose males display two curious behaviors. One, presented by Matthew Fuxjager, is “the winner effect,” a phenomenon where mice that have won fights with other mice are more likely to win subsequent fights. Fuxjager found that the brains of California mice are full of triggers for testosterone, including areas normally associated with reward. “Winning can in fact change the brain,” Fuxjager concluded, a relevant message for an NFL Sunday.

Erin Gleason also uses California mice in her research, but instead of focusing on their fighting habits, she looks at their parenting. The mice are one of the few rodent species where the father and mother share in the care of their pups, and Gleason looked at the role testosterone plays in this behavior. Surprisingly, removing testosterone (by, well, castration) actually decreased the mouse fathers’ parenting skills – the same hormone so intricately involved in making a mouse a good fighter also made them a good Dad, it seems. Moreover, when Gleason looked at the offspring of those castrated dads later in life, they themselves were bad fathers despite no experimenter manipulation of their hormones. Lax parenting was inherited, and hormonal effects rippled down a generation.

2:00 PM – Autism: Faulty Wiring in the Brain?

As I said in my preview, I was looking forward to Thomas Sudhof’s talk about gene mutations associated with the diagnosis of one of the autism spectrum disorders. Sudhof, an MD from Stanford, said that over 100 such mutations have been discovered to date in humans, associated with autism-like symptoms like impaired social communication, repetitive behaviors, or restricted language. The big question, Sudhof asked, is whether all of these genes act upon a common pathway, suggesting a common mechanism for autism that could be the focus of a legitimate therapy.

The answer, Sudhof said, may lie in molecules called neurexins and neuroligins that help neurons connect to each other. Discovered by Sudhof when he went looking for how a black widow spider’s toxin wreaks havoc upon the nervous system, neurexin and neuroligin form a connection between two neurons where neurotransmitters can be released and received. Without those signals, synapses form, but don’t work properly, making the brain like a building where the electrical wiring was installed improperly and the internet doesn’t work (an experience I’ve had today at McCormick Place).

Many of the mutations scientists have associate with autism impact some component of this neurexin-neuroligin system, suggesting that the behaviors of autistic children can be traced back to faulty wiring of the brain. Sudhof has taken some of these human mutations and expressed them in mice, finding that some of them cause social deficits in animals that resemble humans (a preference for interacting with an inanimate object rather than another mouse, for instance).  Sudhof doesn’t think that neurexin and neuroligin are the entire story for autism, but he’s collaborating with other prominent researchers to nail down the genetic culprits most promising for developing therapies that could help autistic children.

12:30 PM – Sex Differences in the Rockstar Room

After wandering through the labyrinth of the massive scientific poster and vendor exhibit room for my first hour at the meeting, I settled into what I dubbed the “rockstar room” back at my first Neuroscience meeting, the location for all of the conference’s featured speakers. Every year, this room appears to grow larger – this year’s space looks like it can hold about 10,000 audience members in identical cushioned chairs, and the 100-foot ceilings and huge black curtains make the staging even more stadium-like. It’s surely the biggest talk any particular neuroscientist ever has to give, and while it’s no competition for U2 at Soldier Field, with 10 video screens, stage-lighting, and headset microphones you usually see on infomercial hosts, the speakers fully live out their on-stage dream.

Only the biggest subjects earn rockstar room status, and the first talk I took in there was focused on a basic element of neuroscience remains poorly understood – sexual differences. There is plenty of evidence for differences between male and female brains, and men and women show vastly different rates of neurological diseases like multiple sclerosis (higher in women) or Parkinson’s (higher in men). But research into how these sexual differences arise – and how to capitalize upon those differences to improve medicine, is still in its early days.

Arthur Arnold, a neuroscientists from UCLA, was one of the first to find a structural difference between the brains of males and females. Yet he didn’t find it in humans, but rather in zebra finches, songbirds where only the males sing as part of their mating ritual. Sure enough, male zebra finches have a much larger area of the brain devoted to song production compared to female finches.

But what tells these brain regions to grow to different sizes? The obvious suspect would be the testes, which circulate testosterone and cause most examples of sexual differentiation. But recently, Arnold’s lab stumbled upon an especially odd bird: a male who lays eggs, dubbed the “e-male.” Although this male has ovaries rather than testes, and thus no circulating testosterone, his brain looks like a male brain, with an enlarged area for song production.

Hence, Arnold has begun studying genes that may influence sexual differences without working through via the testes and ovaries. With specially designed mouse models that tease apart the influence of the gonads versus the influence of other genes on the X or Y chromosomes, Arnold’s group has observed non-hormonal related sex differences in blood pressure, body weight, autoimmune function and pain sensitivity. Now they’ll try to identify the specific genes on the sex chromosomes that may mediate these differences.

10:00 AM – It Begins (A Little Late)

After a day where circumstances got in the way of attending the meeting (long story), I have finally made it down to McCormick Place, successfully picked up my badge, and am ready to binge on science. Even though I’ve been to this meeting several times by now, it’s still intimidating when you first take in the full breadth of the conference in person – badge-wearing conventioneers coalescing on trains and buses and spilling en masse into the MC Escher escalator layout of the convention center and the cathedral-size main room. My schedule doesn’t show any noteworthy big talks until 11:30, so I’m going to spend the first part of my day wandering the endless aisles of exhibitors and poster presentations, and will be back later with the first full report. Stay tuned, updates will be placed in this post.

About Rob Mitchum (526 Articles)

Rob Mitchum is communications manager at the Computation Institute, a joint initiative between The University of Chicago and Argonne National Laboratory.

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