Sorting out Stroking Sensations: Biologists Find Individual Neurons in Skin That React to Massage

Jan. 30, 2013 — The skin is a human being’s largest sensory organ, helping to distinguish between a pleasant contact, like a caress, and a negative sensation, like a pinch or a burn. Previous studies have shown that these sensations are carried to the brain by different types of sensory neurons that have nerve endings in the skin. Only a few of those neuron types have been identified, however, and most of those detect painful stimuli. Now biologists at the California Institute of Technology (Caltech) have identified in mice a specific class of skin sensory neurons that reacts to an apparently pleasurable stimulus.

Left: An image of fluorescent nerve fibers in the spinal cord, viewed through the microscope prior to stimulation. Right: A magnified view showing the increase in fluorescence signal in one specific fiber (boxed area, red color) during stroking with the brush. (Credit: Anderson Lab / Caltech)

More specifically, the team, led by David J. Anderson, Seymour Benzer Professor of Biology at Caltech, was able to pinpoint individual neurons that were activated by massage-like stroking of the skin. The team’s results are outlined in the January 31 issue of the journal Nature.

“We’ve known a lot about the neurons that detect things that make us hurt or feel pain, but we’ve known much less about the identity of the neurons that make us feel good when they are stimulated,” says Anderson, who is also an investigator with the Howard Hughes Medical Institute. “Generally it’s a lot easier to study things that are painful because animals have evolved to become much more sensitive to things that hurt or are fearful than to things that feel good. Showing a positive influence of something on an animal model is not that easy.”

In fact, the researchers had to develop new methods and technologies to get their results. First, Sophia Vrontou, a postdoctoral fellow in Anderson’s lab and the lead author of the study, developed a line of genetically modified mice that had tags, or molecular markers, on the neurons that the team wanted to study. Then she placed a molecule in this specific population of neurons that fluoresced, or lit up, when the neurons were activated.

“The next step was to figure out a way of recording those flashes of light in those neurons in an intact mouse while stroking and poking its body,” says Anderson. “We took advantage of the fact that these sensory neurons are bipolar in the sense that they send one branch into the skin that detects stimuli, and another branch into the spinal cord to relay the message detected in the skin to the brain.”

The team obtained the needed data by placing the mouse under a special microscope with very high magnification and recording the level of fluorescent light in the fibers of neurons in the spinal cord as the animal was stroked, poked, tickled, and pinched. Through a painstaking process of applying stimuli to one tiny area of the animal’s body at a time, they were able to confirm that certain neurons lit up only when stroked. A different class of neurons, by contrast, was activated by poking or pinching the skin, but not by stroking.

“Massage-like stroking is a stimulus that, if were we to experience it, would feel good to us, but as scientists we can’t just assume that because something feels good to us, it has to also feel good to an animal,” says Anderson. “So we then had to design an experiment to show that artificially activating just these neurons — without actually stroking the mouse — felt good to the mouse.”

The researchers did this by creating a box that contained left, right, and center rooms connected by little doors. The left and right rooms were different enough that a mouse could distinguish them through smell, sight, and touch. In the left room, the mouse received an injection of a drug that selectively activated the neurons shown to detect massage-like stroking. In the room on the right, the mouse received a control injection of saline. After a few sessions in each outer room, the animal was placed in the center, with the doors open to see which room it preferred. It clearly favored the room where the massage-sensitive neurons were activated. According to Anderson, this was the first time anyone has used this type of conditioned place-preference experiment to show that activating a specific population of neurons in the skin can actually make an animal experience a pleasurable or rewarding state — in effect, to “feel good.”

The team’s findings are significant for several reasons, he says. First, the methods that they developed give scientists who have discovered a new kind of neuron a way to find out what activates that neuron in the skin.

“Since there are probably dozens of different kinds of neurons that innervate the skin, we hope this will advance the field by making it possible to figure out all of the different kinds of neurons that detect various types of stimuli,” explains Anderson. The second reason the results are important, he says, “is that now that we know these neurons detect massage-like stimuli, the results raise new sets of questions about which molecules in those neurons help the animal detect stroking but not poking.”

The other benefit of their new methods, Anderson says, is that they will allow researchers to, in principle, trace the circuitry from those neurons up into the brain to ask why and how activating these neurons makes the animal feel good, whereas activating other neurons that are literally right next to them in the skin makes the animal feel bad.

“We are now most interested in how these neurons communicate to the brain through circuits,” says Anderson. “In other words, what part of the circuit in the brain is responsible for the good feeling that is apparently produced by activating these neurons? It may seem frivolous to be identifying massage neurons in a mouse, but it could be that some good might come out of this down the road.”

Allan M. Wong, a senior research fellow in biology at Caltech, and Kristofer K. Rau and Richard Koerber from the University of Pittsburgh were also coauthors on the Nature paper, “Genetic identification of C fibers that detect massage-like stroking of hairy skin in vivo.” Funding for this research was provided by the National Institutes of Health, the Human Frontiers Science Program, and the Helen Hay Whitney Foundation.


Story Source:

The above story is reprinted from materials provided byCalifornia Institute of Technology. The original article was written by Katie Neith.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Sophia Vrontou, Allan M. Wong, Kristofer K. Rau, H. Richard Koerber, David J. Anderson. Genetic identification of C fibres that detect massage-like stroking of hairy skin in vivoNature, 2013; 493 (7434): 669 DOI: 10.1038/nature11810
California Institute of Technology (2013, January 30). Sorting out stroking sensations: Biologists find individual neurons in skin that react to massage. ScienceDaily. Retrieved January 31, 2013, from http://www.sciencedaily.com/releases/2013/01/130130152908.htm

Why Are There Redheads? Birds Might Hold the Clues

Jan. 28, 2013 — Red coloration — historically seen as costly in vertebrates — might represent some physiological benefit after all, according to research published in the journal Physiological and Biochemical Zoology.

Barn Swallow, Hirundo rustica, perched on a wire. (Credit: © Eric Isselée / Fotolia)

 

Pheomelanin, which is responsible for red hair and freckles in humans and orange and chestnut coloration in other animals, is known to increase the damage to skin cells and melanoma risk when present in large amounts. Furthermore, its creation involves the consumption of glutathione, a beneficial antioxidant.

In an attempt to unearth the factors favoring the evolution of pheomelanin in spite of its costs, Ismael Galván and Anders P. Møller of the University of Paris-Sud examined the survival from one breeding season to the next of a wild European population of barn swallows, as well as the annual survival rates of 58 species of American birds.

A recent hypothesis claims that the consumption of cysteine (a component of glutathione) that occurs when pheomelanin is produced can be beneficial under conditions of low stress. Cysteine, which is mainly acquired through diet, can be toxic at high levels, so the production of pheomelanin may help to sequester excess quantities of this amino acid.

Galván and Møller measured birds’ blood levels of uric acid and analyzed the coloration of their chestnut throat feathers (an indication of pheomelanin content). When they compared birds that had similar uric acid levels (and therefore similar capacities to excrete excess amino acids), they found that both the European barn swallows and the American birds with larger amounts of pheomelanin in their feathers survived better.

This study is the first to propose that the costs/benefits of pheomelanin may depend on prevailing environmental conditions, and its results suggest that the production of this pigment may even be beneficial in some circumstances. Given that all higher vertebrates, including humans, present pheomelanin in skin, pelage, and plumage, Galván and Møller’s findings increase the scant current knowledge on the physiological consequences of pheomelanin and open new avenues for research that will help us understand the evolution of pigmentation.


Story Source:

The above story is reprinted from materials provided byUniversity of Chicago Press Journals.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Ismael Galván, Anders P. Møller. Pheomelanin-Based Plumage Coloration Predicts Survival Rates in Birds.Physiological and Biochemical Zoology, 2013; : 000 DOI:10.1086/668871
University of Chicago Press Journals (2013, January 28). Why are there redheads? Birds might hold the clues. ScienceDaily. Retrieved January 30, 2013, from http://www.sciencedaily.com/releases/2013/01/130128151930.htm

Skin Has an Internal Clock

ScienceDaily (July 19, 2012) — A research team at Charité – Universitätsmedizin Berlin together with scientists at a company in Hamburg has now discovered that human skin has an internal clock responsible for the time-based steering of its repair and regeneration, among other things.


 

The team published its first results from their basic research in the current issue of Proceedings of the National Academy of Sciences (PNAS).
Our skin is one of the body’s essential organs and perhaps the most versatile: Besides representative, communicative and sensory functions, it serves as our body’s boundary to the environment, forms an active and passive barrier against germs and helps keeping conditions constant for other important systems of the body, even though environmental conditions can change drastically. Frost, heat, sunlight and moisture — a variety of challenges for our skin — have different effects depending on the time of day.
Prof. Achim Kramer’s research team from the field of chronological biology at Charité and Dr. Thomas Blatt from the Skin Research Center in Hamburg have now found out that skin adapts to these time-dependent conditions.
The researchers took cell samples (keratinocytes) from the uppermost layer of skin from young, healthy test persons at various times of the day. Analysis of numerous genes in the keratinocytes showed that important factors for the regeneration and repair of skin cells are regulated by a biological clock. One of these factors, the molecule called the Krüppel-like-factor (Klf9) slows down cell division in the keratinocytes: When the researchers reduced the activity of this factor, they observed faster growth in the skin cell cultures. On the other hand, increased activity of Klf9 was connected with slower cell division. At the same time, it was shown that the stress hormone cortisol also controls the activity of Klf9 and can thus deploy a medical effect on common skin diseases like psoriasis.
The job of the biological clock is to control the exact timing of various processes like cell division, cell differentiation and DNA repair in skin. Prof. Kramer is already looking to the future: “If we understand these processes better, we could target the use of medication to the time of day in which they work best and have the fewest side effects.”

 

Journal Reference:

  1. F. Sporl, S. Korge, K. Jurchott, M. Wunderskirchner, K. Schellenberg, S. Heins, A. Specht, C. Stoll, R. Klemz, B. Maier, H. Wenck, A. Schrader, D. Kunz, T. Blatt, A. Kramer. Kruppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes. Proceedings of the National Academy of Sciences, 2012; 109 (27): 10903 DOI: 10.1073/pnas.1118641109

 

Charité – Universitätsmedizin Berlin (2012, July 19). Skin has an internal clock. ScienceDaily. Retrieved July 21, 2012, from http://www.sciencedaily.com­ /releases/2012/07/120719103608.htm