Imaging Method Reveals Remarkable 'Architecture' of the Working Brain

English
REHOVOT, Israel - December 16, 1997 - With thousands of neurons firing signals in all directions and forming trillions of possible connections, you'd expect the working brain to be a messy place.

Yet a new study conducted by researchers from Max Planck Institute of Psychiatry in Martinsried, Germany, and Israel's Weizmann Institute of Science reveals that brain cells engaged in different tasks in the visual cortex form "mosaics" which are amazingly orderly and elegant.

The study, featured on the cover of December's Journal of Neuroscience, used the optical imaging method developed by Weizmann's Prof. Amiram Grinvald, which has made it possible to provide an extremely detailed map of how the brain is organized when it processes information.
 
"Our maps of the working brain are so orderly they resemble the street map of Manhattan rather than, say, of a medieval European town," says Dr. Mark Huebener of Max Planck.
 
Beyond allowing us to marvel at the beauty of the brain's design, this research may assist in the development of artificial vision systems.

"Over the course of evolution, the mammalian brain developed its sophisticated architecture not in order to provide scientists with pretty pictures but in order to function as efficiently as possible," says Grinvald."Once we fully understand the principles behind this efficiency, we may be able to use them in artificial systems," he says.
 
The research team included Dr. Huebener and Prof. Tobias Bonhoeffer of Max Planck Institute of Psychiatry, and Dr. Doron Shoham and Prof. Grinvald of the Weizmann Institute's Neurobiology Department.


A regular geometric pattern

In the new research and in two preceding studies conducted by Grinvald and colleagues, optical imaging was used to examine the spatial relationship between neurons responsible for three aspects of vision - perception of depth, shape and color - and revealed that they form remarkably orderly interrelated mosaic-like patterns.

 
Groups of neurons responsible for depth perception are organized in parallel columns, while the "shape-savvy" neurons form patterns resembling pinwheels (first visualized by Bonhoeffer and Grinvald). The centers of the pinwheels are aligned along the centers of the columns in relatively straight lines, as are the clusters of neurons responsible for color perception. Moreover, the pinwheels' "spokes" always cross the borders of the columns at a right angle.
 
Obviously, these regular geometric relationships between different groups of working neurons are governed by specific rules that are far from random and apparently serve to maximize the efficiency with which the brain processes visual information.
 

Extremely high resolution

Scientists have long suspected that, despite its overwhelming complexity, there is method to the brain's "madness": as long as 30 years ago, Nobel-winning neuroscientists Torsten Wiesel and David Hubel talked about the "architecture" of the brain at work."Architecture" implies that once we know how to look, we'll discover that the networks of functioning neurons form orderly structures depending on their task.


Yet until recently, brain imaging techniques did not provide sufficient resolution to reveal such structures.It was precisely for this purpose that Grinvald - while working in Prof. Wiesel's laboratory at Rockefeller University - developed the optical imaging method used in the current study.
 
Optical imaging makes it possible to visualize the detailed organization of the brain at work because it can map the brain's functional architecture with an extremely high resolution, allowing scientists to observe structures as small as 0.05 millimeter in size. In contrast, the resolution of other imaging methods is too low to accomplish this kind of mapping: functional magnetic resonance imaging, or f-MRI, provides a resolution of only 1-3 millimeters, and positron emission tomography, approximately 5 millimeters.All of these three imaging techniques are based on the interaction between the brain's electrical activity and the circulation of blood in its microvessels. In fact, optical imaging research is currently being used to improve the resolution of f-MRI.

Prof. Grinvald, who holds the Helen and Norman Asher Professorial Chair in Brain Research, is head of the Murray H. and Meyer Grodetsky Center for Research of Higher Brain Functions and of the Wolfson Center for Applied Scientific Research in Functional Brain Imaging at the Weizmann Institute.

This work was supported by the Max-Planck Gesellschaft and by grants from the Minerva Foundation, the Human Frontier Science Program, the European Commission Biotech Program, and Ms. Margaret Enoch of New York.

 

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.
Life Sciences
English

Windows on your Mind: Weizmann Institute Scientists Reveal That Imagination Can Enhance Visual Perception

English
REHOVOT, Israel - December 9, 1997 - Conjuring up images in the "mind's eye" enhances our ability to see what's really there, Weizmann Institute scientists have found.

However, imagination greases the wheels of perception only when the images are drawn from short-term memory, the researchers report in the current issue of the Journal of Cognitive Neuroscience.

In contrast, reaching into our long-term memory to recall an image may interfere with our ability to perceive visual data. "It seems that, under certain circumstances, activating short-term memory can change the 'hard wiring' of the visual cortex, allowing people to see what they couldn't see before," says Dr. Alumit Ishai, who conducted this research during her doctoral studies under the guidance of Prof. Dov Sagi of the Weizmann Institute's Neurobiology Department.

The research also supports the idea that short- and long-term visual memory may be governed by separate mechanisms in the brain.


Reality and Imagery

Anyone who has looked for a friend in a crowd intuitively knows how visual imagery works: conjuring up a mental image makes it easier to identify the friend when he actually appears.As Prof. Sagi explains, memory and perception constantly work together because whenever we see something, we identify it based on images stored in memory."Without memory, the world we perceive would be incomprehensible." he says. "However, if memory is given too much weight, the result is hallucination."


But does the brain work in the same way when we imagine an object and when we actually see it? And does reaching into our memory to recall an image make it easier or more difficult to complete visual tasks? Philosophers and scientists have long sought answers to these questions, but previous studies have produced conflicting results.

The new research by Ishai and Sagi explains why: previous studies made no distinction between images drawn from short- and long-term memory.


Short-Term Versus Long-Term Memory

The Institute researchers have, for the first time, quantified the effects of visual imagery on perception by creating experiments in which subjects viewed subtle points of light, known as Gabor signals, on a computer screen. By varying the points' intensity, they were able to establish the exact threshold of brightness at which the light became visible to the participant.
 

First, participants viewed a computer display in which three Gabor signals appeared along a straight line, with the flanking signals situated at various distances from the central signal. As the distance between the flanking signals was increased, participants found it more difficult to see the central signal, eventually losing sight of it altogether. Then, the scientists adjusted the brightness of the central signal in order to establish the new threshold at which participants could see the target.
 
At this point, memory was called into action. Sagi and Ishai showed the participants a screen with only one Gabor signal, asking them to imagine the flanking signals they had recently seen. The results were surprising: When participants imagined the flanking signals, they were able to see the target more easily than in the previous trial. By activating their short-term memory, the participants lowered the threshold of brightness at which visual perception could occur. They actually improved their own ability to see.
 
Further experimentation linked this phenomenon specifically to short-term memory. The threshold of perception was lowered only when the participants were asked to imagine the flanking signals soon after seeing them on the screen. As more time elapsed, the flanking signals presumably "slipped" into the participants' long-term memory bank; calling up the image raised the vision threshold, making the target signal more difficult to see.
 
These results indicate that short- and long-term memory are represented differently in the brain and are controlled by different neural mechanisms, although it is not yet clear what these mechanisms are.
 
Sagi and Ishai hope that with further study of this phenomenon, it may someday be possible to harness the natural power of memory to "open the eyes" of those who suffer from vision problems.

This research was supported by the Israel Science Foundation administered by the Israel Academy of Sciences and Humanities, and by the Charles H. Revson Foundation.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.
Life Sciences
English

Tune Into This: Weizmann Institute Study Provides Evidence For a Radio-Like Mechanism in the Brain

English
REHOVOT, Israel - October 14, 1997- Research conducted at the Weizmann Institute of Science may give a whole new meaning to the phrase "stay tuned." Institute scientists have found evidence that when the brain interprets sensory input, it uses a mechanism remarkably similar to that of an FM radio.

In a study reported in the October 14 issue of the Proceedings of the National Academy of Sciences , the researchers describe how the brain uses this radio-like mechanism to "tune in" to a particular frequency, allowing information gathered through touch to be translated into data about external objects.

This research provides a possible new explanation for the way the brain processes sensory information.
 
"We hope that our study will contribute to the deciphering of the neural code, the way in which information is encoded by the sensory organs and decoded by the brain," says research team leader Dr. Ehud Ahissar of the Weizmann Institute's Neurobiology Department. He conducted the study with departmental colleague Dr. Sebastian Haidarliu and Dr. Miriam Zacksenhouse of the Technion-Israel Institute of Technology. "Cracking" the neural code would immensely advance brain research, just as the discovery of the genetic code revolutionized genetics and molecular biology.
 

Like an FM receiver

When we touch an object, the nerve endings in our skin send electric neural signals to the brain. Until now, scientists studying touch - or, for that matter, other senses - have focused on identifying the brain cells that receive these signals and on assessing the signals' intensity.

 
However, according to Weizmann Institute researchers, this is not the whole story of how the brain actually knows what it's being told by the senses. In the new study, they argue that the timing of the signals also plays a crucial role in this process.
 
"We found that certain circuits in the brain can work on the same principle as an FM radio," says Dr. Ahissar.
 
In frequency modulation (FM) receivers, the radio is tuned to a particular frequency, or station. During the broadcast this frequency is being constantly altered, or modulated, and the receiver translates these modulations into different sounds.
 
Similarly, the brain appears to be tuned to its own "radio stations." In the past decade, scientists discovered that the sensory cortical areas of the brain contain cells that oscillate at regular frequencies due to intrinsic mechanisms that do not rely on external stimuli.
 
In their study in PNAS , Ahissar and colleagues show that neural signals generated by touch modulate the oscillation frequency of these cells.
 
Because the cortex oscillations are regular and persistent, they provide the brain with a "yardstick" against which the timing of incoming signals can be compared. The comparison probably takes place in the thalamus, which receives input both from the cortical areas containing the oscillating cells and from the external sensory stimuli.
 
It is this comparison that allows the brain to track the timing, or frequency, of the incoming signals, enabling it to decode the information about the object being touched.
 
Imagine, for example, that you rub your finger against a ribbed surface, such as corduroy fabric. Nerve endings in the skin would send a signal to the brain every time they hit upon one of the fabric's ridges. The thinner and closer-spaced the ridges, the more frequent the signals would be. Thus, the frequency of the signals encodes sensory information about the surface.
 
In fact, this may be the reason we need to move the finger over a surface in order to better assess its texture: movement allows us to assess the distribution of sensory input over time and better define the object being touched.
 
"The timing of the sensory signals appears to be an inherent part of the neural code," says Ahissar. "In fact, this timing contains so much information about the external world that it would be surprising if the brain made no use of it."


Clarifying the mechanism

The researchers conducted their study on rats, that twitch their whiskers when scouring for food. The rats' brains translate the input from their whiskers into data about the location of objects.

 
The whiskers twitch rapidly, at a rate of about eight motions per second. These motions "notify" the oscillating neurons in the cortex to tune in to a "transmission frequency" of about 8 Hz. When the whiskers hit upon an object, they trigger additional neural signals to the brain, which perturb, or modulate, the regular 8 Hz transmission. The timing of these perturbations is determined by the object's location. Therefore, it allows the brain to create an internal representation of the object's whereabouts.
 
"The brains of primates contain similar oscillating cells, which are tuned to the characteristic frequencies generated when the fingertips rub against an external object," says Ahissar. "Thus, the human brain could use similar FM-radio-like mechanisms to process information obtained through touch and perhaps through other senses as well."
 
In an extension of this research, Weizmann scientists are currently seeking to demonstrate that the same principle applies when the brain decodes information perceived through other senses, particularly vision.
 
This research was funded in part by the Minna-James-Heineman Foundation, Germany; the Israel Science Foundation; and the United States-Israel Binational Science Foundation, Israel.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.
Life Sciences
English

Pacman in the Brain: Protein Chews up Vital Memory Chemical

English
What does the human brain have in common with a popular video game and a carnivorous flower? At least one thing, it turns out. A team from Israel's Weizmann Institute of Science and France's Pasteur Institute found that proteins called glutamate receptors, which enable brain cells to absorb glutamate, a chemical vital for memory and learning, are strikingly similar in shape to both Pacman and the Venus flytrap.

In a study reported in Neuron, the scientists created a 3-D computer model of one type of glutamate receptor that can serve as a template for all others. The model revealed that glutamate receptors have two hemispherical lobes facing each other and held together by a hinge of amino acids.

It also showed that these receptors share the characteristic behavior of both Pacman and the Venus flytrap: they sit on cell membranes with their "mouths" wide open and shut their "jaws" to nab passing glutamate molecules. This nabbing leads to the opening of sodium and potassium channels in the cell, which triggers a chain of molecular processes, some of which are involved in memory.

Three-D protein models are extremely important because they not only help clarify the proteins' properties but can also be used in the computerized search for new molecules with therapeutic potential.

"Our model may become a valuable tool for developing drugs for a variety of glutamate-related disorders, including stroke, head trauma, epilepsy and perhaps also for failing memory in Alzheimer disease," says team leader Prof. Vivian Teichberg of Weizmann's Neurobiology Department.

Teichberg's team turned to computers because glutamate receptors do not crystallize and therefore cannot be studied by X-ray crystallography, the usual method of determining 3-D protein structures.

The receptor model was built using a set of computer programs that combined information about the protein's amino acids with the known structure of two bacterial proteins believed to be evolutionary predecessors of glutamate receptors. The scientists then conducted various lab experiments confirming that the model accurately represents the actual receptor.

Computerized drug development, in which the new model may be used, works on the "Cinderella's shoe" principle: the computer program tries to match the receptor's "shoe," or binding site, with the "foot," 3-D models of numerous potentially useful molecules, until it finds one that fits, and the molecule is then tested in the lab.

The model created by Teichberg's team may, for example, help develop new synthetic molecules that would compete with glutamate, blocking its receptors and thereby limiting its activity in cases such as stroke and head trauma, where excessive glutamate is known to cause damage by killing brain cells.

 

Prof. Teichberg, who holds the Louis and Florence Katz-Cohen Chair of Neuropharmacology, worked with doctoral students Yoav Paas and Itzhak Mano of the Weizmann Institute's Neurobiology Department, Dr. Miriam Eisenstein, head of the Molecular Modeling Unit in the Weizmann Institute's Chemical Services, and Prof. Anne Devillers-Thiry and laboratory assistant Fran ois Medevielle of the Pasteur Institute.

The study was supported by the Minerva Foundation, Munich, Germany, the Golden Charitable Trust, and the Weizmann Institute's Leo and Julia Forchheimer Center for Molecular Genetics and the Kimmelman Center for Biomolecular Assembly.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.
Life Sciences
English

New Concept Explains Why Mammals Can't Repair Central Nervous System Damage

English
REHOVOT, Israel -- September 17, 1996 -- Why is it that humans and other mammals are left permanently paralyzed or otherwise handicapped by injuries to the central nervous system, while fish and other lower life forms can repair such injuries and resume normal lives?

A study led by Prof. Michal Schwartz of the Weizmann Institute of Science, reported in the September issue of the FASEB Journal, provides an explanation that links the mammalian inability to repair central nerve damage with evolution -- and offers hope for developing an effective treatment for injuries to the spinal cord and other parts of the central nervous system.

Evolution allowed mammals to have complex brains, capable of acquiring new knowledge throughout a lifetime. But, according to Schwartz, along with this asset came a disadvantage: the brain and the rest of the central nervous system lost their self-healing ability, which exists in lower vertebrates.

Schwartz says this loss probably occurred as a result of the critical need to protect the brain from remodeling by the immune system: while immune cells normally help to heal damaged tissue, their access to the brain would disrupt the complex and dynamic neuronal networks that build up during an individual s lifetime.

There seems to have been an evolutionary trade-off, Schwartz says. Higher animals protected their central nervous system from invasion by the immune system, but paid the price of forfeiting their ability to regenerate injured nerves. Thus, an evolutionary advantage that protects the healthy brain turns into a disadvantage in the case of injury. Generally, when tissue damage occurs, immune cells known as macrophages swarm to the injured site, where they remove damaged cells and release substances that promote healing.

The central nervous system in mammals is an exception in this regard: when damaged, it is not effectively assisted by the immune system. Schwartz s team found that this is because the mammalian central nervous system contains an active component that suppresses the macrophages.

As a result, relatively few macrophages are recruited to central nervous system injuries, and those that are recruited fail to become activated and are ineffective. We have shown that the immune system's assistance is just as vital for the repair of the mammalian central nervous system as it is for any other tissue, Schwartz says. However, because of a suppressive mechanism which seems to have developed in the course of evolution, this assistance does not operate.

The explanation emerged from a series of experiments conducted by a Weizmann Institute Neurobiology Department team that included Orly Lazarov-Spiegler, Adi Ben Zeev-Brann, David Hirschberg and Dr. Vered Lavie, working with Dr. Arieh S. Solomon of the Sheba Medical Center near Tel Aviv.


Educating Immune Cells


The scientists examined whether this obstacle to nerve regeneration could be overcome by using macrophages that had been educated by special treatment outside the body. For this purpose, rat macrophages were first isolated and then activated through incubation with injured sciatic nerves, which, as part of the peripheral nervous system, are capable of regeneration.

The scientists then transplanted the activated macrophages into injured rat optic nerves, which, as part of the central nervous system, normally do not regenerate. The pre-activated macrophages induced the optic nerves to regrow. Macrophages may be the missing link in the process of wound-healing in the central nervous system, Schwartz says.

Transplanting suitably activated macrophages into injured nerves may help overcome the central nervous system s failure to respond after injury. According to Schwartz, the procedure might eventually be developed into a novel, practical and potent treatment to repair central nervous system injuries, and particularly to restore movement in cases of spinal injury although such a development may still take many years. This approach would in effect mean turning the evolutionary clock back to the distant past, Schwartz says.

Prof. Schwartz holds the Maurice and Ilse Katz Chair of Neuroimmunology at the Weizmann Institute. The study was supported in part by the Alan T. Brown Foundation of Nerve Paralysis, and by the donation of Ralph Colton to the Weizmann Institute/University of Michigan scientific exchange program.

The FASEB Journal is the official publication of the Federation of American Societies for Experimental Biology.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.
 
Life Sciences
English

Scientists Brainstorm to Find Cure for Tourette Syndrome

English
REHOVOT, Israel -- July 10, 1996 -- An intensive effort to shed light on Tourette syndrome -- the humiliating genetic disorder known for causing sufferers to twitch and swear repetitively -- brought six Yale University professors to Israel's Weizmann Institute of Science recently for a meeting of leading scientific minds.

The professors from Yale's Child Study Center met with about 130 scientists, neurologists and psychologists from Israel and Holland at a one-day symposium with the aim of encouraging basic research, such as that done at the Weizmann Institute, to merge with clinical research to find a cure for the condition, which is believed to affect up to one in 2,000 people worldwide.

It is the first time that Yale and the Institute have come together to work on Tourette syndrome, although they have a long-standing collaboration agreement which has sponsored other projects. Opening the symposium, Yale's Prof. Donald Cohen said Tourette syndrome was considered an exotic, bizarre disease from the time it was first identified 100 years ago until recently. He said it was only in the past decade that real progress had been made in understanding and controlling it with an explosion of new drugs and advances in understanding brain chemistry.

"Those of us working on Tourette syndrome felt this was a good time for reassessing the state of the field and outlining future new directions," Prof. Cohen said. "We hope that an event like today's will sharpen the focus of research and be a major turning point."

Tourette syndrome is a chronic genetic disorder characterized by bouts of motor and vocal tics -- repetitive, involuntary actions -- that first show up in childhood and grow progressively worse. Although it is best known for causing sufferers to swear uncontrollably, in fact only about 30 percent do so; most vocal tics merely comprise repetitive words or noises. The syndrome is about four times as common in men as in women, and is often accompanied by other conditions such as hyperactivity, obsessive-compulsive behavior and attention problems.

In an introductory overview, Yale's Prof. James Leckman said the latest understanding of the disorder had come from autopsies on Tourette sufferers which showed an imbalance in brain chemicals and a lack of development in one particular section of their brains: in a normal, right-handed adult, the left side of the brain was enlarged, but in a right-handed Tourette sufferer it was not, resembling the brain of a one-year-old child.

Greater understanding of these findings could be gained by performing imaging on the working brain, an area of research in which Weizmann Institute scientists have made important advances.

The Institute's Prof. Amiram Grinvald told the conference about insights into the workings of the brain provided by his optical imaging method, which makes it possible to observe actual brain functions with unprecedented resolution. Another promising new direction is in the study of brain chemicals, particularly dopamine and serotonin -- areas in which the Institute's Profs. Rabi Simantov and Menahem Segal have made prominent contributions.

Such research can help clarify whether pharmaceutical drugs merely suppress the symptoms of Tourette or actually affect the underlying disorder. The Weizmann Institute's Prof. Vivian Teichberg, who was one of the main organizers of the meeting, said it was hoped that creating greater awareness of the disorder among basic researchers would speed the development of a cure.

"Scientists working in their ivory towers of basic research can benefit very much from encounters with clinicians working at the beds of patients, while the clinicians can benefit from the knowledge that accumulates at the benches of scientists involved in basic research," Prof. Teichberg told the symposium. "If what we are doing here does contribute to a possible solution for sufferers of Tourette syndrome and their families, that will be the best reward."

The symposium was sponsored by the Yale-Weizmann endowment fund, Gate Pharmaceuticals, the US Tourette Syndrome Association and the Maurice and Gabriela Goldschleger Conference Foundation at the Weizmann Institute of Science. Prof. Grinvald holds the Helen and Norman Asher Chair of Brain Research; Prof. Segal, the Harry and Leona Levine Chair of Neurosciences; and Prof. Teichberg, the Louis and Florence Katz-Cohen Chair of Neuropharmacology.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot,Tour Israel.
 
Life Sciences
English
Yes

Developing New Therapies for Spinal Cord Injury

English
Prof. Michal Schwartz
 
In the early 1980s, Prof. Michal Schwartz, an immunologist, started to explore the cross-talk between the immune and nervous systems.
 

Application

 
New therapies for spinal cord injury based on original concepts proposed by Schwartz are being developed and tested in clinical trials by Proneuron, a company in Kiryat Weizmann.
 
Prof. Michal Schwartz
Life Sciences
English

How Does the Brain Take Shape?

English
Fluorescent microscope photo of mouse cortical nerve cells (neurons) in culture infected with lentiviruses that express green fluorescent protein
 
 

 

we use our brain to shape the world around us; but first, the basic design of our interior world must unfold in our developing brain. What genetic and neural mechanisms give rise to our personality? Which fine tune our sexual behavior? What code programs a mother’s love or our reaction to stress? Personality already begins to develop in the embryonic brain, though the process continues well after birth. Scientists in the Institute’s Faculty of Biology are investigating various mechanisms that shape our personalities, both in the growing brain and in the genes and nerve networks of the adult brain.

Dr. Alon Chen studies the genetic roots of such phenomena as stress and anxiety. He has found, for instance, that the presence of certain proteins determines an animal’s response to emotional or physiological stress. Other research in Chen’s lab reveals a genetic connection between emotional stress and such disorders as diabetes, obesity and heart disease.

Dr. Gil Levkowitz uses the transparent zebrafish to observe the formation of the hypothalamus – a brain region that regulates, among other things, metabolism, emotional and physical stress, and social behavior. Combining fluorescent imaging with genetic techniques, he follows developing nerve circuits and traces genetic factors that affect physiological function.

Dr. Tali Kimchi is curious about the differences between the male and female brain – as well as the mechanisms for the mutual attraction between them. She has demonstrated how to turn a mothering, feminine mouse into a macho “Casanova” by flipping just one genetic switch. In her lab, which resembles the set of the television show Big Brother, cameras and microphones tape the lives of genetically altered lab mice day and night. Here, the scene reveals how the brain controls such activities as sex recognition, competition for mates and raising pups.

 
Drs. Gil Levkowitz, Tali Kimchi and Alon Chen
 
 

 

Dr. Alon Chen’s research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Irwin Green Alzheimer’s Research Fund; Gerhard and Hannah Bacharach, Fort Lee, NJ; Mark Besen and the Pratt Foundation, Australia; and Roberto and Renata Ruhman, Brazil. Dr. Chen is the incumbent of the Philip Harris and Gerald Ronson Career Development Chair.

Dr. Tali Kimchi’s research is supported by the Carl and Micaela Einhorn-Dominic Brain Research Institute; Rina Mayer, Israel; and Esther Smidof, Switzerland.

Dr. Gil Levkowitz’s research is supported by the Dekker Foundation; the Minna James Heineman Stiftung; the Women’s Health Research Center funded by the Bennett-Pritzker Endowment Fund, the Marvelle Koffler Program for Breast Cancer Research, the Harry and Jeanette Weinberg Women’s Health Research Endowment, and the Oprah Winfrey Biomedical Research Fund. Dr. Levkowitz is the incumbent of the Tauro Career Development Chair in Biomedical Research.

 
 
Fluorescent microscope photo of mouse cortical nerve cells (neurons) in culture infected with lentiviruses that express green fluorescent protein. From the lab of Dr. Alon Chen
Life Sciences
English

The Bat Has Landed

English
 

Dr. Nachum Ulanovsky and Dr. Yossi Yovel. New angle on sonar

 

 

 

 

 

 

 

 

 

 

 

 

 

Need to track a moving object in the dark? The best method might not be shining your flashlight directly at it. New research on bats shows you could do better by angling the beam a bit to the left or right of your object. The illumination will be dimmer toward the edges of the expanding cone of light, but it will be easier to make out the object’s direction as it moves in relation to the brighter center. In research that recently appeared in Science, Dr. Nachum Ulanovsky and postdoctoral fellow Dr. Yossi Yovel of the Weizmann Institute’s Neurobiology Department showed that bats, which “see” with beams of sound waves, locate an object by aiming their sonar beam to either side of an object, catching it on the cone’s fainter slope, rather than at the central peak.

Animal sonar, or echolocation, is a type of active sensing: The animal must send out a signal in order to get back information on its surroundings. It works remarkably like the sonar that submarines use to find enemy ships: The bats (or ships) emit a sound and listen for the echo, accurately judging the type and location of objects around them by the changes in the sound waves as they’re reflected back. This gives biologists studying echolocation a unique research tool: The mathematical formulas that have been worked out by sonar engineers can generally be applied also to animal echolocation. In keeping with this tradition of applying mathematical thinking to animal sonar, the Weizmann scientists theorized that there should be a trade-off in efficiency between the detection of an object and determining its exact location. For a bat, this could mean that a bug hidden among leaves is best found by focusing with the peak intensity of the sound beam, whereas a large moth flitting out in the open – easy to detect but hard to locate – could best be tracked by aiming the beam off-center to make use of its maximum slope; this turns out to be the most sensitive strategy for detecting changes in the moth’s location.

But are the bats actually behaving according to this prediction – that is, are they able to fit their echolocation strategy to the situation? To answer this question, a research team headed by Ulanovsky trained bats to locate and land on a large black sphere placed randomly in a completely dark room. The bats had to rely solely on echolocation to navigate. A string of special microphones arrayed around the room’s walls traced the sound waves the bats emitted, while two infrared video cameras tracked their flight patterns.

The large Egyptian fruit bats in Ulanovsky’s lab have a unique echolocation system. Unlike many smaller bat species that emit regularly-spaced ultrasonic squeaks, these bats produce their signals in clicks, two at a time. The researchers thought that these double clicks might hold some clues to the bats’ localization strategies. Sure enough, the team, which included Prof. Cynthia Moss and research student Ben Falk from the University of Maryland, found a pattern: The first set of double clicks was aimed left and then right, the next set right and then left. As the bats closed in for a landing, they continued to throw their sound beams to alternate sides of the sphere, just where the mathematical formula predicted they would be most effective. The sphere was designed to be easily detectable, meaning the bat’s optimal strategy was one of localization. To create a situation in which detection was needed as well as localization, the scientists installed a large panel behind the sphere that echoed the sound waves back to the bats’ ears. Now, instead of identifying the sphere’s echo in a quiet room, they had to pick it up out of a battery of noise. This time, as the bats approached their target, they began to narrow their sweep and aim the beams more or less directly toward the sphere.

Large Egyptian fruit bat
 

Ulanovsky: “We were surprised to find that no one had asked these questions before us. Not only did we show that the optimal method for tracking an object is to catch it off-center, on the slope of a beam, we also demonstrated that bats are capable of balancing between detection and localization, and adopting the best strategy according to the particular need.” Active sensing takes place in many situations: Sonar and radar bounce off moving vessels or airplanes, dolphins and whales echolocate in the oceans, dogs track objects by sniffing, and our eyes move in all directions as they interact with our surroundings. Even bacteria use a type of chemical sensing to move toward or away from nearby substances. Ulanovsky and Yovel believe that what works for bats may well work for other organisms: In the future, scientists might find that “sensing on the slope” could be a useful strategy for any or all of these.


Dr. Nachum Ulanovsky’s research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the J&R Foundation; and Rita and Steven Harowitz, Tiburon, CA.

 
 
Dr. Nachum Ulanovsky and Dr. Yossi Yovel. New angle on sonar
Life Sciences
English

Scents and Sensibility

English
 
Prof. Noam Sobel and Yaara Yeshurun. Remembering the smell
 
 
From Proust’s madeleines to the overbearing food critic in the movie Ratatouille who’s transported back to his childhood by the aroma of stew, artists have long been aware that some odors spontaneously evoke strong memories. Why do smells figure this way in the memory?
 
Graduate student Yaara Yeshurun, together with Profs. Noam Sobel and Yadin Dudai of the Weizmann Institute’s Neurobiology Department, thought that the key might lie not necessarily in childhood but rather in the first time a smell is encountered in the context of a particular object or event. In other words, the initial association of a smell with an experience will somehow leave a unique and lasting impression in the brain.
 
To test this idea, the scientists devised an experiment: First, in a special smell laboratory, subjects viewed images of 60 objects, each presented simultaneously with either a pleasant or an unpleasant odor generated by a machine called an olfactometer. Next, the subjects were put in an fMRI scanner to measure their brain activity as they reviewed the images they’d seen and attempted to remember which odor was associated with each. The whole test was then repeated – images, odors and fMRI – with the same images but different odors accompanying each. Finally, the subjects came back a week later to be scanned in the fMRI again. They viewed the objects one more time and were asked to recall the odors they associated with them.
 
The scientists found that after one week, even if the subject recalled both odors equally, the first association revealed a distinctive pattern of brain activity. The effect was seen whether the smell was pleasant or unpleasant. This unique representation showed up in the hippocampus, a brain structure involved in memory, and in the amygdala, a brain structure involved in emotion. The pattern was so profound, that just by looking at the brain activity within these regions following the initial exposure, the scientists could predict which associations would come up a week later. To see if other sensory experiences might share this tendency, the scientists repeated the entire experiment using sounds rather than smells; they found that sounds did not arouse a similar distinctive first-time pattern of activity. In other words, these results were specific to the sense of smell. “For some reason, the first association with smell gets etched into memory,” says Sobel, “and this phenomenon allowed us to predict what would be remembered one week later, solely on the basis of brain activity.”
 
Yeshurun: “As far as we know, this phenomenon is unique to smell. Childhood olfactory memories may be special not because childhood is special, but simply because those years may be the first time we associate something with an odor.”

 
Prof. Noam Sobel’s research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the J&R Foundation; the Eisenberg-Keefer Fund for New Scientists; and Regina Wachter, New York, NY.
Prof. Noam Sobel and Yaara Yeshurun.
Life Sciences
English

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