“It’s all in your head” is more than a catchy phrase; it’s a fairly accurate description of how the human body functions. From blood pressure to appetite to food metabolism, much of the body’s chemistry is controlled by the brain. In a study published recently in Developmental Cell, a team of scientists led by Dr. Gil Levkowitz of the Weizmann Institute has revealed the exact structure of one crucial brain area in which biochemical commands are passed from the brain cells to the bloodstream, and from there to the body.

 

The brain area in question, the neurohypophysis, is located at the base of the brain, where it is an interface between nerve fibers and blood vessels. Here, some of the major brain-body interactions take place: the nerve cells release into the blood vessels the hormones that regulate a series of vital body processes, including the balance of fluids and uterine contractions in childbirth. The neurohypophysis has been studied for more than a century; but now, in the Weizmann Institute-led study, the scientists have developed new genetic tools that allowed them to re-examine the exact three-dimensional arrangement of this brain structure, along with clarifying the cellular and molecular processes leading to its formation.

 

Since the human neurohypophysis, composed of tens of thousands cells, is exceedingly complex, the scientists performed the research on live embryos of zebrafish, which offer a unique model for studying the vertebrate brain. As these embryos are entirely transparent and lend themselves to genetic manipulation with relative ease, the scientists could observe the actual formation of the fish neurohypophysis under a microscope. The findings apply to humans because this part of the brain is built similarly in all vertebrates. The research was conducted in Dr. Levkowitz’s lab in the Molecular Cell Biology Department by Ph.D. student Amos Gutnick together with Dr. Janna Blechman. The Weizmann scientists worked in collaboration with Dr. Jan Kaslin of Monash University, Australia; Drs. Lukas Herwig, Heinz-Georg Belting and Markus Affolter of the University of Basel, Switzerland; and Dr. Joshua L. Bonkowsky of the University of Utah, United States.

 

 

But does the fact that the two periodicities – spatial and temporal – always occur together mean that one causes the other? In rats, it is impossible to separate them; but Ulanovsky suspected that the bats he studies – Egyptian fruit bats – might not exhibit such a neat correlation. In a previous study of bat place cells, he had noted oscillations that were very different from those of rats, and he hypothesized that this dissimilarity might apply to grid-cell activity, as well.

To find out, the researchers first had to locate the bats’ entorhinal cortex and pinpoint the exact location of the grid cells – a long process undertaken by the Weizmann researchers in collaboration with the Trondheim lab of Witter, a noted expert on brain anatomy. Ulanovsky and Yartsev then carefully inserted tiny electrodes into the area containing grid cells and recorded their activity as the bats crawled around the floor of a box, replicating the rat experiments as closely as possible.
 

Their findings showed that the bat grid cells fired in a neat hexagonal array nearly identical to that of rats; the similarity extended to the smallest details of the hexagons’ properties. But the oscillations in time were completely different: Instead of regular waves, the bats’ brains revealed short bouts of oscillation interspersed with longer quiescent periods – putting them at odds with the model. Further mathematical analysis showed that the grid patterns remain unchanged even if oscillations are identified and removed from the analysis. In other words, there is no real correlation between the oscillations and the grids; oscillations cannot be the cause of the grid cells’ unique ordered patterns.

By disproving the first model, Ulanovsky and his colleagues have lent strong support to the second, alternative model, which proposes that the pattern arises because the cells work as a network. The hexagonal layout is explained by the fact that a hexagon is the one formation in which all the activity nodes are equidistant, leading to the minimum-energy, most stable pattern of the network model. This principle is seen elsewhere in nature, for instance in honeycombs, in which the hexagon shape provides a strong structure that yields a minimum-energy, stable configuration.
 

Dr. Nachum Ulanovsky's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Clore Center for Biological Physics; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Irving B. Harris Foundation; the estate of Fannie Sherr; Mr. and Mrs. Steven Harowitz, San Francisco, CA; and the European Research Council.
 

 

The fact that certain smells cause us pleasure or disgust would seem to be a matter of personal taste. But new research at the Weizmann Institute shows that odors can be rated on a scale of pleasantness, and this turns out to be an organizing principle for the way we experience smell. The findings, which appeared today in Nature Neuroscience, reveal a correlation between the response of certain nerves to particular scents and the pleasantness of those scents. Based on this correlation, the researchers could tell by measuring the nerve responses whether a subject found a smell pleasant or unpleasant.

Our various sensory organs have evolved patterns of organization that reflect the type of input they receive. Thus the receptors in the retina, in the back of the eye, are arranged spatially for efficiently mapping out visual coordinates. The structure of the inner ear, on the other hand, is set up according to a tonal scale. But the organizational principle for our sense of smell has remained a mystery: Scientists have not even been sure if there is a scale that determines the organization of our smell organ, much less how the arrangement of smell receptors on the membranes in our nasal passages might reflect such a scale.

A team headed by Prof. Noam Sobel of the Weizmann Institute’s Neurobiology Department set out to search for the principle of organization for smell. Hints that the answer could be tied to pleasantness had been seen in research labs around the world, including that of Sobel, who had previously found a connection between the chemical structure of an odor molecule and its place on a pleasantness scale. Sobel and his team thought that smell receptors in the nose – of which there are some 400 subtypes – could be arranged on the nasal membrane according to this scale. This hypothesis goes against the conventional view, which claims that the various smell receptors are mixed -- distributed evenly, but randomly, around the membrane.

In the experiment, the researchers inserted electrodes into the nasal passages of volunteers and measured the nerves’ responses to different smells in various sites. Each measurement actually captured the response of thousands of smell receptors, as these are densely packed on the membrane. The scientists found that the strength of the nerve signal varies from place to place on the membrane. It appeared that the receptors are not evenly distributed, but rather, that they are grouped into distinct sites, each engaging most strongly with a particular type of scent. Further investigation showed that the intensity of a reaction was linked to the odor’s place on the pleasantness scale. A site where the nerves reacted strongly to a certain agreeable scent also showed strong reactions to other pleasing smells and vice versa: The nerves in an area with a high response to an unpleasant odor reacted similarly to other disagreeable smells. The implication is that a pleasantness scale is, indeed, the organizing principle for our smell organ.

But does our sense of smell really work according to this simple principle? Natural odors are composed of a large number of molecules – roses, for instance, release 172 different odor molecules. Nonetheless, says Sobel, the most dominant of those determine which sites on the membrane will react the most strongly, while the other substances make secondary contributions to the scent.

“We uncovered a clear correlation between the pattern of nerve reaction to various smells and the pleasantness of those smells. As in sight and hearing, the receptors for our sense of smell are spatially organized in a way that reflects the nature of the sensory experience,” says Sobel. In addition, the findings confirm the idea that our experience of smells as nice or nasty is hardwired into our physiology, and not purely the result of individual preference. Sobel doesn’t discount the idea that individuals may experience smells differently. He theorizes that cultural context and personal experience may cause a certain amount of reorganization in the smell membrane over a person’s lifetime.
 

 

This research was carried out by Hadas Lapid, Drs. Sagit Shushan and Anton Plotkin in the group of Prof. Noam Sobel, together with Dr. Elad Schneidman of the Weizmann Institute’s Neurobiology Department and Dr. Yehudah Roth of Wolfson Hospital in Holon, Prof. Hillary Voet of the Hebrew University of Jerusalem and Prof. Thomas Hummel of Dresden University, Germany.