Friday, April 22, 2011

The Personal is Professional?

Last summer, when I was developing the curriculum for my ORDER teaching module, I started with a plan that hit the highlights of every biology course I've ever taken and every popular science book I've ever read: cool experiments, wacky phenotypes, stories about the history of science, elegant examples of fundamental concepts. I wanted to borrow from the best in order to supplement the story of my own research. At an early course development meeting, Dr. Lynn listened to my ideas and then gently suggested that I rethink the entire curriculum. He reminded me that I was supposed to design a unique new course. "You are the selling point," he told the Teacher-Scholars. He strongly encouraged all of us to spend class time discussing our personal journeys into academia and our reasons for choosing to study the things that we study. We were positioned as models and mentors for our undergraduate students, and he wanted them to learn about our lives as well as our dissertations.

I was initially resistant to the idea. Why spend time on my undergraduate research experiences when I could be talking about Nobel laureates? But, ultimately, I heeded Dr. Lynn's advice and centered my classes squarely on my thesis and the topics surrounding it (including a day on animal research, during which I told personal stories about how that aspect of my work makes me feel, in addition to more formal discussions of ethics and regulations). It's impossible to say whether my students would have preferred my original plan, but I think they enjoyed the module. And, I've noticed that my own blog reading habits seem to confirm what Dr. Lynn was emphasizing: science is more compelling when scientists feel like real people rather than detached manuscript authors. I love Research Blogging, but I find myself more likely to skim those posts on other blogs, and I've noticed that my own posts attract more comments when I talk about my personal experiences than when I review an article.

Sometimes I skip writing here because I don't feel like I have time to compose a well-researched scholarly analysis on whatever topic has popped into my head. I feel pressure to meet a high standard because I blog under my real name and I want future professional contacts who read this to think of me as a Serious Scientist. Especially after learning that my adviser regularly includes links to this blog when she writes me letters of recommendation! (The realization left me feeling both proud and terrified, which seems to be the optimal emotional state for PIs to evoke in their trainees.)

But, what I value most about science blogs is the community, and how fellow bloggers give me a window into the lives of my peers and near-peer role models. If that's what I'm getting out of it, perhaps I should put more in, and write more of that sort of content.

I hope to follow through with more self-reflective writing in the future, although the thought still weirds me out a little. I am debating whether or not to write a series of posts on my experiences with some neurologically-relevant phenomena (I swear this is not code for recreational drug use). Many of my favorite bloggers who write about the intersection of science with family responsibilities, personal crises, and social factors are pseudonymous. Given my... "nymity?"... I'd appreciate thoughts on the line where community-building crosses into over-sharing.

Friday, April 15, 2011

Hunger Hormone Enhances Sense of Smell

ResearchBlogging.orgThe smell of coffee wafting through the air this morning may have inspired me to write about this Journal of Neuroscience paper from Dr. Jenny Tong and colleagues at the University of Cincinnati. Their work showed the effects of the appetite-stimulating hormone ghrelin on the olfactory system. It seems only logical that hunger should have effects on food-seeking behavior, including the detection of food smells. This study sheds light on the mechanisms through which ghrelin modulates olfactory processing in both rats and humans.

But first, a little background on the wonders of the olfactory system. I am not a systems or behavioral neuroscientist, but if I was, I would totally study olfaction. The olfactory system appeals to my interests in cellular, molecular, and developmental neuroscience. We all have tons of olfactory receptor neurons (ORNs), each of which somehow expresses only a single odorant receptor gene (out of approximately 1000, in humans). And each ORN, depending on which receptor it expresses, sends its axon into the olfactory bulb, where it joins up with the axons of all other ORNs expressing that receptor in a beautiful structure called a glomerulus. To get a sense of how cool that is, observe this image from Feinstein and Mombaerts (2004) showing mouse ORNs expressing an olfactory receptor called M71, labelled in blue:

Mouse ORNs, from Feinstein and Mombaerts, 2004

Check it out: neurons in the olfactory epithelium inside the nose (left side of the image) are exposed to the air, which allows them to bind to inhaled odorant molecules. They send their axons through a bone (the ethmoid) in olfactory nerve fibers that converge on the appropriate glomerulus (near the upper right corner). Glomeruli occur in stereotyped locations, residing in the same part of the olfactory bulb in every individual. What's not shown here is that there are ~2000 distinct glomeruli in the bulb, and ORNs always find the right ones. The olfactory system, in short, is really cool.

Studying olfaction doesn't just provide a great excuse to say words like "glomerulus" (Latin for "a small ball;" from the same root as "conglomerate," as in to roll a bunch of disparate things into a ball). The system is a minor miracle of carefully regulated gene expression, axon pathfinding, and tricky neural coding used to translate the activation of ORNs into a downright Proustian experience. Perhaps that's why the first people to figure some of this stuff out received a Nobel Prize.

But enough of my olfactory fangirling. Back to Dr. Tong and her colleagues, who were interested in how this elegant system functions after the glomeruli have formed and the animal is out there in the world, sniffing for food. Specifically, they wanted to know how changes in nutritional state affect olfaction. Do hungry animals differ from satiated animals in their food-seeking olfactory processes? To test this, the researchers specifically measured two factors important for functional olfaction: sniffing behavior and olfactory detection thresholds (that is, how sensitive are the ORNs to very low levels of an odorant?). They found that ghrelin enhances both.

Neuroendocrinologists have identified a bunch of hormones and neuropeptides that contribute to sensations of hunger and satiety, but the main "hunger hormone" is ghrelin. Ghrelin is produced in the stomach and circulates throughout the body to stimulate feelings of hunger and increase food intake. (After learning about ghrelin in our first year systems neuroscience course, my classmates and I frequently invoked it at lunch time. "Are you ghrelin?" "Yeah, I'm ghrelin like a felon!" ... it was a timely joke in 2008, okay?) Interestingly, ghrelin receptors are found on facial motor neurons involved in sniffing movements, which implies that this hormone may regulate food-seeking behavior in part by inducing animals to start sniffing for their next meal.

For this study, the researchers first showed that ghrelin receptors are found not only in "sniff neurons" in the facial motor nuclei, but also in the olfactory bulb itself. This provides a mechanism through which ghrelin can modulate not just sniffing but also olfactory sensitivity. They confirmed that ghrelin increases olfactory sensitivity in rats by measuring whether the rats could detect very low levels of an odor in their drinking water. After rats were conditioned to avoid an odor (odorized water was paired with a drug that made the rats feel sick), Dr. Tong and colleagues measured how much the rats drank from a bottle of pure water versus a bottle containing very low concentrations of the odor. Rats that were given an infusion of ghrelin avoided the odorized water, even when the odor was diluted by a factor of 10-10. Untreated rats still drank from the most dilute odorized water bottles, indicating that they were unable to detect the odor at such low concentrations. This implies that ghrelin binding to olfactory brain regions lowers the threshold of odor detection -- in other words, 'hungry' animals are more sensitive to smells. There does seem to be a maximum level of ghrelin-mediated olfactory sensitivity, however: rats that fasted overnight were more sensitive to odors than rats that had recently eaten, but treating the fasting rats with ghrelin did not further improve their ability to detect very weak odors.

Dr. Tong et al. also showed that ghrelin increased exploratory sniffing in rats "using a video-based, fully automated behavior analysis system (HomeCageScan, Clever Sys) that recognizes, records, and quantifies the movement of the nose tip while the animal was either fully or partially reared in a home-cage environment." (That is not even close to the funniest/weirdest sentence from an olfaction paper, either. My favorite is from Stowers et al., 2002: "The time required to discover a hidden cookie (latency) is similar in mutant and wild-type mice," followed by a graph of "cookie latency." Cookie latency is a standard measure in the olfactory behavior literature. This particular paper contains other LOLs, though -- it's about how mice that lack a certain ion channel lose the ability to distinguish between males and females, and thus display indiscriminate mating behavior. End immature parenthetical.)

The researchers also measured sniffing behavior in humans. Here, I think, is where the Materials and Methods section of the paper becomes really awesome:

Sniffing behavior was evaluated using the sniff magnitude test (SMT) as described previously. Briefly, a canister was placed ∼2 cm beneath the nose, and subjects were instructed to take a single, natural sniff as would be taken when sampling a perfume or food. The stimuli used were as follows: nonodorized air, baby power odor (baby power fragrance oil, 50% dilution, The Good Scents Co.), banana odor (isoamyl acetate, 1% dilution, Sigma-Aldrich), and tomato odor and rosemary chicken odor (both undiluted, formulated by Givaudan). Three sniffing trials were collected for each odorant and six for air. A specialized software program identified the initiation of sniffing, recorded sniff pressure at 10 ms intervals, summed sniff pressures, and measured each sniff's duration during a 5 s sampling period. The sum of the pressure values was defined as the sniff magnitude. The subjects were also asked to rate the pleasantness of the odors immediately after each trial using a visual analog scale [scores ranging from −5 (slightly unpleasant) to 15 (best smell ever)]. The order of stimulus presentation was randomized. The average sniff magnitude and odor pleasantness ratings were used for data analysis.

Subjects were given the SMT after an infusion of saline or of varying levels of ghrelin. The result was that the cumulative sniff magnitude was significantly increased by all doses of ghrelin, but not by saline. Ghrelin treatment had no significant effect on the pleasantness rating of any odor, however. (I wonder why the scale doesn't go below -5? Artificial banana odor sounds more than "slightly unpleasant" to me. Certainly nowhere near "best smell ever.")

In sum, ghrelin increases an olfactory food-seeking behavior (sniffing) in both rats and humans, as well as olfactory sensitivity in rats. No measurements of odor detection threshold were made in humans, however, which I found a bit disappointing. It would be unethical to induce conditioned odor aversions in humans, but it seems like it should be possible to ask people to discriminate between scented and unscented samples, or between two different odors at very low concentrations. Perhaps it was too difficult to design that study, or to recruit enough participants interested in receiving i.v. ghrelin infusions. (Perhaps a "ghrelin like a felon" TV commercial would be helpful?)

One surprising result of this study was that ghrelin levels had no effect on sniffing for food odors vs. non-food orders, nor on how participants rated the pleasantness of individual odors. Other studies have shown that feelings of hunger increase human preferences for food odors, but these results imply that those effects are not due specifically to the action of ghrelin. Rather, ghrelin seems to upregulate food-seeking behaviors like sniffing without necessarily affecting the hedonic value (pleasantness) of food-related cues. Perhaps other appetite and satiety hormones, like orexin and leptin, are involved in food odor preferences in hungry individuals. This just goes to show that even the most basic biological drives (everyone eats!) aren't as simple as we might expect.

References

Tong J, Mannea E, Aimé P, Pfluger PT, Yi CX, Castaneda TR, Davis HW, Ren X, Pixley S, Benoit S, Julliard K, Woods SC, Horvath TL, Sleeman MM, D'Alessio D, Obici S, Frank R, & Tschöp MH (2011). Ghrelin enhances olfactory sensitivity and exploratory sniffing in rodents and humans. Journal of Neuroscience, 31 (15), 5841-5846 PMID: 21490225

Feinstein P, & Mombaerts P (2004). A contextual model for axonal sorting into glomeruli in the mouse olfactory system. Cell, 117 (6), 817-31 PMID: 15186781

Stowers L, Holy TE, Meister M, Dulac C, & Koentges G (2002). Loss of sex discrimination and male-male aggression in mice deficient for TRP2. Science, 295 (5559), 1493-500 PMID: 11823606

Wednesday, April 6, 2011

OIST Developmental Neurobiology Short Course

I'm very pleased to announce that I will be spending two weeks of my summer in Okinawa, Japan to participate in the Okinawa Institute of Science and Technology's Developmental Neurobiology Course. Given how much fun I had at last summer's Gordon Conference on Neural Development, I'm sure I'll return with a head full of ideas for exciting new experiments, just in time to have them shot down at my next committee meeting. No, but seriously, it sounds really cool. And as a bonus, all my travel expenses are covered by OIST.

I have to admit that I am a little hesitant about traveling to a far-off location for several weeks by myself. It's not like I'll be wandering around lost in a foreign country -- science conferences and courses are very structured, and all of our sight-seeing will be supervised. But I've never traveled to a meeting without classmates or labmates before, and I've never traveled internationally for work at all. My nervousness has reminded me that I'm privileged to live in close proximity to most major scientific conferences. I don't envy the jet-lagged folks from around the world at SfN each year, and now I'll get to walk a mile in their shoes.

Despite my qualms about the travel, I'm excited about the course. I'm especially looking forward to the lectures and labs on invertebrate development, since most of my research experience is in mammalian systems. I have wondered if I should try to do a postdoc using flies or worms instead of mice, but my only experience with Drosophila was in sophomore year bio lab, and I've never even seen a C. elegans nematode in person. The course will provide some hands-on experience and a lot of interaction with experts in these systems, so I hope to come away with a better idea of what it would be like to work in an invertebrate lab.

In general I'm left a little stunned that someone wants to give me an all-expense-paid science vacation. I'm pulling a 13-hour work day today (not typical; it's a long story) and haven't had a work-free weekend in quite a while, but I have to say that the perks of being a grad student are pretty cool.

Monday, April 4, 2011

Wicked Burn, PhD

Me (giving lab meeting): I'm not sure if this protein motif is important or not. It seems conserved, but then again, if you stare at the amino acid sequence long enough, you start to see all kinds of stuff.
Labmate: Like the face of Jesus?
Me: I've never looked for Jesus in a protein sequence. But I did BLAST my own name once, to look for MARIANI peptides.
Adviser: ...Wow.
Me: Bet you didn't know I was that much of a dork, huh?
Adviser: Oh, no. I knew you were that much of a dork.