Sense and Body Function 2007


January, 2007

Advanced technology has allowed scientists to peer deeper than ever before into the inner workings of the brain, expanding our understanding of the complex relationship between the brain, the senses, and body function. This vast area extends from specialized genomic tools to explore the mechanics of rapid-eye-movement sleep to studies of the influence of circadian clocks on feeding, as well as identifying a section of the brain devoted solely to face recognition. Other studies in 2006 revealed new information about hearing, smell, taste, and sight, answering old questions and raising new ones.

Hearing: Regenerating Hair Cells in Mammals

Sensorineural hearing loss, currently an irreversible condition, is the most common type of deafness in the United States. It is caused by damage to specialized inner-ear hair cells, from  aging, exposure to loud noises, and side effects from certain medications. Scientists interested in developing new therapies for certain types of hearing loss got a boost in 2006 from research that suggests that these specialized hair cells, vital to hearing, may be able to regenerate. 
Although damaged sensory cells in the inner ear, or cochlea, of birds and other lower vertebrates can regenerate, cells in cochlea in mammals, including humans, cannot. Hair cells have long been a target of research aimed at developing new treatments for sensorineural hearing loss. In a study reported in Nature, Neil Segil, Andy Groves, and colleagues at the House Ear Institute in Los Angeles discovered that a gene known as p27Kip1 prevents cell division in the inner ear.1

The researchers studied mouse sensory cells in culture. They found that this gene was switched off in newborn mice, allowing the supporting cells to proliferate and differentiate into hair cells. Studies of cultures from two-week-old mice, however, revealed that this gene, p27 for short, was now switched on, halting cell division. However, cells from two-week-old mice genetically altered to lack the p27 gene were able to make hair cells, suggesting that by silencing the gene, researchers may be able to stimulate inner ear hair cell growth to restore hearing.

Hair cell 
Hear, hair: An image of a hair cell from a high-power scanning electron microscope shows hair bundles projecting from the surface of the cell. Researchers have found in mice that silencing a gene allows hair cell growth that could restore hearing.  (Image courtesy of the House Ear Institute) 

While this process has been shown only in mouse cultures, the work holds promise for the development of new therapeutics to reverse deafness in humans.  

Why Faces Are Familiar

A study published in Science adds weight to one side of a long-standing debate among neuroscientists about whether the brain is divided into specialized areas dedicated to performing a specific task.2 In the study, scientists at Harvard Medical School and the University of Bremen in Germany have identified an area of the visual cortex in which almost all of the neurons are specialized for just one task: face perception.

Using functional magnetic resonance imaging, a team led by Margaret Livingstone identified three areas of the cortex in macaque monkeys believed to be important in face recognition. Monkeys were shown 96 images, including pictures of faces, bodies, fruits, gadgets, hands, and scrambled grid patterns. Scientists then recorded neuronal impulses from individual cells in the largest of these three brain regions. They found that almost all (97 percent) of visually responsive neurons were 50 times more likely to respond to faces than to the other visual stimuli. In fact, the only other images that sparked a response from these neurons were round objects similar to the shape of faces.

Strong physiological similarities between the macaque brain and the human brain suggest that humans may have the same specialized cells solely devoted to facial recognition. Using imaging to analyze the process of face detection could lead to newer methods for lie detection (see also Neuroethics).

Pheromone Detection

The brain systems of many animals allow for detection of pheromones, chemical signals that help animals attract mates. However, the human brain appears to lack this ability, a scientific mystery given recent findings that suggest that humans can respond to pheromones. One possibility is that the olfactory epithelium, which contains neurons that recognize ordinary odors, may also detect pheromones.

Scientists at the Fred Hutchinson Cancer Research Center in Seattle set out to explore the epithelium’s potential role in pheromone detection in mice. In research reported in Nature, Stephen Liberles and Linda Buck identified a set of olfactory receptors in the mouse nose called trace amine-associated receptors, or TAARs.3  

The receptors are different from those that sense odors, and earlier studies suggest that some are activated by compounds in pheromone-rich mouse urine. In their study, Liberles and Buck found that one of the compounds TAARs recognize, isoamylamine, is thought to act as a pheromone that accelerates puberty in female mice.

This, coupled with other findings, suggests that TAARs may provide an alternate pheromone-detection method. Because the genes that encode TAARs are also found in fish and humans, it is possible that humans use these receptors to detect pheromones.

REM Sleep Circuitry

Scientists discovered rapid-eye-movement (REM) sleep, associated with dreaming, more than 50 years ago. But just how the brain switches from REM to non-REM sleep remains unknown.

Researchers from Harvard Medical School released findings in 2006 that suggest a new model for how the brain controls the switch into and out of REM sleep. The study, reported in Nature by Clifford Saper and colleagues, also examines how the dream states and loss of muscle tone seen during REM sleep are activated.4

Previous models stressed interactions between cholinergic neurons, which are active during REM sleep, and monoaminergic neurons, which are silent during REM sleep. However, the model the Harvard team developed, which the scientists call the “flip-flop switch,” found that deactivating these two types of neurons had little effect on REM sleep. 
Rather, they found that a reciprocal interaction between neurons releases a chemical messenger called gamma-aminobutyric acid, which is widely distributed in the brain, binds to neurons, and reduces their activity.
Problems in regulating this interaction may explain a number of puzzling sleep disorders, such as REM behavior disorder, in which patients act out their dreams, and hypnagogic hallucinations, in which they have dreamlike hallucinations while still awake.

Attempts to develop sleep-inducing drugs have generally ignored the various stages of sleep. Understanding the regulation of these stages could lead to better treatments for sleep disorders.

Circadian Clocks and Feeding

Scientists have long known that when animals are given access to food only during their normal sleep cycles, they will alter their sleep patterns and biological functions to be awake and active when food is available. Two independent studies published in 2006 by teams at Harvard Medical School and the University of Texas Southwestern Medical Center may explain what enables animals to make this switch.

One team, led by Saper at Harvard, focused on a region of the brain called the dorsomedial nucleus of the hypothalamus, or DMH, which communicates with parts of the brain involved in feeding, energy consumption, the regulation of sleep and wakefulness, and body temperature, among other processes. The scientists, reporting in Nature Neuroscience, found that the DMH can override the brain’s biological clock and establish a new clock time to take advantage of food availability.5  

The second study, published by Masashi Yanagisawa and colleagues in Proceedings of the National Academy of Sciences, shows that the DMH neurons contain a normally nonfunctional clock that, when faced with restricted food availability, synchronizes itself to the time the food is available, allowing the DMH to establish its own circadian rhythms that override the brain’s biological clock.6 

The findings from both studies offer new targets for future research on circadian clocks and feeding, work that one day could have implications for treating obesity.

Hypothalamus illustration 

Eating and sleeping to survive: The dorsomedial nucleus of the hypothalamus (DMH) coordinates cycles of sleep and wakefulness, feeding, and body temperature, among others. Research shows that this region can override the brain’s clock, the suprachiasmatic nucleus (SCN), according to when food is available. (Illustration by Benjamin Reece) 

 

Sour-Taste Receptor Identified

Humans savor foods with the aid of taste buds on the tongue that detect five specific tastes: bitter, sweet, salty, sour, and umami (the flavor of monosodium glutamate). Scientists have identified receptors that detect three of these: bitter, sweet, and umami.

Studies in 2006 by two independent research teams identified a protein that allows humans and some animals to sense sour tastes, including flavors that warn against eating spoiled or unripe food. The research, reported in Nature and Proceedings of the National Academy of Sciences, identified the protein as PKD2L1. It is present in some taste buds but absent in those that recognize sweet, bitter, and umami tastes.7,8

A group led by Charles Zuker at the University of California, San Diego, who reported the work in Nature, genetically engineered mice lacking PKD2L1. The animals responded to other tastes, but when given citric acid, vinegar, and other sour flavors, the mice did nothing.

Meanwhile, a team led by Duke University researcher Hiroaki Matsunami suggested in Proceedings of the National Academy of Sciences that the findings could lead to a better understanding of how the brain processes sensory information and could one day be used by the manufacturing industry to alter the taste of foods.

Stem Cells and Vision

In vision research, findings point to embryonic stem cells as a possible treatment for age-related macular degeneration. The disease, the leading cause of blindness among people over 65, is caused by a deterioration of the retina and macula, which is located at the center of the retina and allows for detailed, central vision.

Retinal pigment epithelium cells, which line the base of the retina, can be damaged in some types of macular degeneration. In the study, reported in Cloning and Stem Cells, a team at Oregon Health and Science University led by Raymond Lund transformed embryonic stem cells into these retinal pigment epithelium cells, and then injected the cells into the eyes of rats with eye disease.9 About six weeks later, the scientists examined the rats’ vision and found that those that received the transformed stem cells had retained much of their sight, while the untreated rats were nearly blind.

In a similar study, researchers led by Robin Ali at University College London transplanted the cells that form the receiving cells of the retina, the photoreceptors.10 Taken together, these studies indicate a possible application of stem cells and other primitive cells to the treatment of macular degeneration.

Although the findings are promising, the scientists cautioned that the rat eye disease is unlike macular degeneration in humans, and that more studies are needed to determine whether stem cells can be used to treat the human form of the disease.