Sleep Boosts Production of Brain Support Cells

Animal study shows genes involved in brain repair, growth turned on during slumber

Sleep increases the reproduction of the cells that go on to form the insulating material on nerve cell projections in the brain and spinal cord known as myelin, according to an animal study published in the September 4 issue of The Journal of Neuroscience. The findings could one day lead scientists to new insights about sleep’s role in brain repair and growth.

Scientists have known for years that many genes are turned on during sleep and off during periods of wakefulness. However, it was unclear how sleep affects specific cells types, such as oligodendrocytes, which make myelin in the healthy brain and in response to injury. Much like the insulation around an electrical wire, myelin allows electrical impulses to move rapidly from one cell to the next.

In the current study, Chiara Cirelli, MD, PhD, and colleagues at the University of Wisconsin, Madison, measured gene activity in oligodendrocytes from mice that slept or were forced to stay awake. The group found that genes promoting myelin formation were turned on during sleep. In contrast, the genes implicated in cell death and the cellular stress response were turned on when the animals stayed awake.

“These findings hint at how sleep or lack of sleep might repair or damage the brain,” said Mehdi Tafti, PhD, who studies sleep at the University of Lausanne in Switzerland and was not involved with this study.

Additional analysis revealed that the reproduction of oligodendrocyte precursor cells (OPCs) — cells that become oligodendrocytes — doubles during sleep, particularly during rapid eye movement (REM), which is associated with dreaming.

“For a long time, sleep researchers focused on how the activity of nerve cells differs when animals are awake versus when they are asleep,” Cirelli said. “Now it is clear that the way other supporting cells in the nervous system operate also changes significantly depending on whether the animal is asleep or awake.”

Additionally, Cirelli speculated the findings suggest that extreme and/or chronic sleep loss could possibly aggravate some symptoms of multiple sclerosis (MS), a disease that damages myelin. Cirelli noted that future experiments may examine whether or not an association between sleep patterns and severity of MS symptoms exists.

Creating a ‘Window to the Brain’

A team of University of California, Riverside researchers have developed a novel transparent skull implant that literally provides a “window to the brain”, which they hope will eventually open new treatment options for patients with life-threatening neurological disorders, such as brain cancer and traumatic brain injury.

The team’s implant is made of the same ceramic material currently used in hip implants and dental crowns, yttria-stabilized zirconia (YSZ). However, the key difference is that their material has been processed in a unique way to make it transparent.

Since YSZ has already proven itself to be well-tolerated by the body in other applications, the team’s advancement now allows use of YSZ as a permanent window through which doctors can aim laser-based treatments for the brain, importantly, without having to perform repeated craniectomies, which involve removing a portion of the skull to access the brain.

The work also dovetails with President Obama’s recently-announced BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, which aims to revolutionize the understanding of the human mind and uncover new ways to treat, prevent, and cure brain disorders. The team envisions potential for their YSZ windows to facilitate the clinical translation of promising brain imaging and neuromodulation technologies being developed under this initiative.

“This is a case of a science fiction sounding idea becoming science fact, with strong potential for positive impact on patients,” said Guillermo Aguilar, a professor of mechanical engineering at UC Riverside’s Bourns College of Engineering (BCOE).

Aguilar is part of 10-person team, comprised of faculty, graduate students and researchers from UC Riverside’s Bourns College of Engineering and School of Medicine, who recently published a paper “Transparent Nanocrystalline Yttria-Stabilized-Zirconia Calvarium Prosthesis”  about their findings online in the journal Nanomedicine: Nanotechnology, Biology and Medicine.

Laser-based treatments have shown significant promise for many brain disorders. However, realization of this promise has been constrained by the need for performing a craniectomy to access the brain since most medical lasers are unable to penetrate the skull. The transparent YSZ implants developed by the UC Riverside team address this issue by providing a permanently implanted view port through the skull.

“This is a crucial first step towards an innovative new concept that would provide a clinically-viable means for optically accessing the brain, on-demand, over large areas, and on a chronically-recurring basis, without need for repeated craniectomies,” said team member Dr. Devin Binder, a clinician and an associate professor of biomedical sciences at UC Riverside.

Although the team’s YSZ windows are not the first transparent skull implants to be reported, they are the first that could be conceivably used in humans, which is a crucial distinction. This is due to the inherent toughness of YSZ, which makes it far more resistant to shock and impact than the glass-based implants previously demonstrated by others. This not only enhances safety, but it may also reduce patient self-consciousness, since the reduced vulnerability of the implant could minimize the need for conspicuous protective headgear.

Brain Wiring Quiets the Voice Inside Your Head

Researchers find nerve circuits connecting motion and hearing

During a normal conversation, your brain is constantly adjusting the volume to soften the sound of your own voice and boost the voices of others in the room. This ability to distinguish between the sounds generated from your own movements and those coming from the outside world is important not only for catching up on water cooler gossip, but also for learning how to speak or play a musical instrument.

Now, researchers have developed the first diagram of the brain circuitry that enables this complex interplay between the motor system and the auditory system to occur.

The research, which appears Sept. 4 in The Journal of Neuroscience, could lend insight into schizophrenia and mood disorders that arise when this circuitry goes awry and individuals hear voices other people do not hear.

"Our finding is important because it provides the blueprint for understanding how the brain communicates with itself, and how that communication can break down to cause disease," said Richard Mooney, Ph.D., senior author of the study and professor of neurobiology at Duke University School of Medicine. "Normally, motor regions would warn auditory regions that they are making a command to speak, so be prepared for a sound. But in psychosis, you can no longer distinguish between the activity in your motor system and somebody else’s, and you think the sounds coming from within your own brain are external."

Researchers have long surmised that the neuronal circuitry conveying movement — to voice an opinion or hit a piano key — also feeds into the wiring that senses sound. But the nature of the nerve cells that provided that input, and how they functionally interacted to help the brain anticipate the impending sound, was not known.

In this study, Mooney used a technology created by Fan Wang, Ph.D., associate professor of cell biology at Duke, to trace all of the inputs into the auditory cortex — the sound-interpreting region of the brain. Though the researchers found that a number of different areas of the brain fed into the auditory cortex, they were most interested in one region called the secondary motor cortex, or M2, because it is responsible for sending motor signals directly into the brain stem and the spinal cord.

"That suggests these neurons are providing a copy of the motor command directly to the auditory system," said David M. Schneider, Ph.D., co-lead author of the study and a postdoctoral fellow in Mooney’s lab. "In other words,they send a signal that says ‘move,’ but they also send a signal to the auditory system saying ‘I am going to move.’"

Having discovered this connection, the researchers then explored what type of influence this interaction was having on auditory processing or hearing. They took slices of brain tissue from mice and specifically manipulated the neurons that led from the M2 region to the auditory cortex. The researchers found that stimulating those neurons actually dampened the activity of the auditory cortex.

"It jibed nicely with our expectations," said Anders Nelson, co-lead author of the study and a graduate student in Mooney’s lab. "It is the brain’s way of muting or suppressing the sounds that come from our own actions."

Finally, the researchers tested this circuitry in live animals, artificially turning on the motor neurons in anesthetized mice and then looking to see how the auditory cortex responded. Mice usually sing to each other through a kind of song called ultrasonic vocalizations, which are too high-pitched for a human to hear. The researchers played back these ultrasonic vocalizations to the mice after they had activated the motor cortex and found that the neurons became much less responsive to the sounds.

"It appears that the functional role that these neurons play on hearing is they make sounds we generate seem quieter," said Mooney. "The question we now want to know is if this is the mechanism that is being used when an animal is actually moving. That is the missing link, and the subject of our ongoing experiments."

Once the researchers have pinned down the basics of the circuitry, they could begin to investigate whether altering this circuitry could induce auditory hallucinations or perhaps even take them away in models of schizophrenia.

Primate calls, like human speech, can help infants form categories

Human infants’ responses to the vocalizations of non-human primates shed light on the developmental origin of a crucial link between human language and core cognitive capacities, a new study reports.

Previous studies have shown that even in infants too young to speak, listening to human speech supports core cognitive processes, including the formation of object categories.

Alissa Ferry, lead author and currently a postdoctoral fellow in the Language, Cognition and Development Lab at the Scuola Internationale Superiore di Studi Avanzati in Trieste, Italy, together with Northwestern University colleagues, documented that this link is initially broad enough to include the vocalizations of non-human primates.

"We found that for 3- and 4-month-old infants, non-human primate vocalizations promoted object categorization, mirroring exactly the effects of human speech, but that by six months, non-human primate vocalizations no longer had this effect — the link to cognition had been tuned specifically to human language," Ferry said.

In humans, language is the primary conduit for conveying our thoughts. The new findings document that for young infants, listening to the vocalizations of humans and non-human primates supports the fundamental cognitive process of categorization. From this broad beginning, the infant mind identifies which signals are part of their language and begins to systematically link these signals to meaning.

Furthermore, the researchers found that infants’ response to non-human primate vocalizations at three and four months was not just due to the sounds’ acoustic complexity, as infants who heard backward human speech segments failed to form object categories at any age.

Susan Hespos, co-author and associate professor of psychology at Northwestern said, “For me, the most stunning aspect of these findings is that an unfamiliar sound like a lemur call confers precisely the same effect as human language for 3- and 4-month-old infants. More broadly, this finding implies that the origins of the link between language and categorization cannot be derived from learning alone.”

"These results reveal that the link between language and object categories, evident as early as three months, derives from a broader template that initially encompasses vocalizations of human and non-human primates and is rapidly tuned specifically to human vocalizations," said Sandra Waxman, co-author and Louis W. Menk Professor of Psychology at Northwestern.

Waxman said these new results open the door to new research questions.

"Is this link sufficiently broad to include vocalizations beyond those of our closest genealogical cousins," asks Waxman, "or is it restricted to primates, whose vocalizations may be perceptually just close enough to our own to serve as early candidates for the platform on which human language is launched?"

(Image: Corbis)

Single tone alerts brain to complete sound pattern

The processing of sound in the brain is more advanced than previously thought. When we hear a tone, our brain temporarily strengthens that tone but also any tones separated from it by one or more octaves. A research team from Utrecht and Nijmegen published an article on the subject in the journal PNAS on 2 September.

We hear with our brain. The cochlea picks up sound vibrations but the signals produced as a result are processed by the brain, using known patterns. If, for example, you briefly hear a weak tone, your hearing focuses on that tone and suppresses any frequencies around it. This makes it easier to notice any relevant sounds in your surroundings. The present research has shown that this ‘auditory attention filter’ is much more complex than believed until now: frequencies that have an octave relationship with the target tone are also heard better.

John van Opstal, professor of Biophysics at Radboud University: ‘This test proves that the brain prepares for a more extensive pattern of tones, even if the person just hears a single test tone or if he has a tone in mind. These extra tones in the pattern were not sounded during the experiment, but the brain complements the information received from the cochlea. This is scientifically interesting. Audiology, for example, at present places great emphasis on the cochlea.’

Octave relationship
The subjects undergoing the experiment did not have an easy time. For an hour they listened to unstructured noise containing very soft tones that they had to detect. Every few seconds they were presented with a tone of 1000 Hz, the cue. Then during one of two time intervals, a very quiet, short second tone was sounded. The subject had to indicate in which of the two intervals they had heard the second tone. It became apparent that tones having an octave relationship with the cue were all heard better, and those around the cue were heard less well. An octave is a well-known term in music, indicating the distance between two tones, the frequencies of which have a 2-to-1 relationship. 

Voice
Van Opstal: ‘We wanted to gather data on the auditory attention filter around the target tone. When we made the range larger than other researchers had done previously, more peaks suddenly appeared. This was a complete surprise to us. One possible explanation could be that the hearing system has evolved in order to hear sounds made by members of an animal’s own species (voices in the case of humans) in noisy surroundings. Vocalisations always consist of harmonic complexes of several simultaneous tones having an octave relationship with each other.’

Hearing aid
The researchers, who work at Utrecht University, the UMC Utrecht Brain Center and Radboud University Nijmegen, can easily think up applications for this fundamental research. If, for example, someone no longer hears high tones because of damage to the cochlear hair cells, the hearing aid can be adjusted in such a way that it converts those tones so they sound one or more octaves lower. Since the brain itself ‘fills in’ tones with an octave relationship, that person’s perception should then become more normal. It is also important for commercial sound producers to know how tones are perceived. That is why Philips Research is involved in this research in their department ‘Brain, Body and Behavior’.

A fly’s hearing

UI study shows fruit fly is ideal model to study hearing loss in people

If your attendance at too many rock concerts has impaired your hearing, listen up.

University of Iowa researchers say that the common fruit fly, Drosophila melanogaster, is an ideal model to study hearing loss in humans caused by loud noise. The reason: The molecular underpinnings to its hearing are roughly the same as with people.

As a result, scientists may choose to use the fruit fly to quicken the pace of research into the cause of noise-induced hearing loss and potential treatment for the condition, according to a paper published this week in the online Early Edition of the journal Proceedings of the National Academy of Sciences.

“As far as we know, this is the first time anyone has used an insect system as a model for NIHL (noise-induced hearing loss),” says Daniel Eberl, UI biology professor and corresponding author on the study.

Hearing loss caused by loud noise encountered in an occupational or recreational setting is an expensive and growing health problem, as young people use ear buds to listen to loud music and especially as the aging Baby Boomer generation enters retirement. Despite this trend, “the molecular and physiological models involved in the problem or the recovery are not fully understood,” Eberl notes.

Enter the fruit fly as an unlikely proxy for researchers to learn more about how loud noises can damage the human ear. Eberl and Kevin Christie, lead author on the paper and a post-doctoral researcher in biology, say they were motivated by the prospect of finding a model that may hasten the day when medical researchers can fully understand the factors involved in noise-induced hearing loss and how to alleviate the problem. The study arose from a pilot project conducted by UI undergraduate student Wes Smith, in Eberl’s lab.

“The fruit fly model is superior to other models in genetic flexibility, cost, and ease of testing,” Christie says.

The fly uses its antenna as its ear, which resonates in response to courtship songs generated by wing vibration. The researchers exposed a test group of flies to a loud, 120 decibel tone that lies in the center of a fruit fly’s range of sounds it can hear. This over-stimulated their auditory system, similar to exposure at a rock concert or to a jack hammer. Later, the flies’ hearing was tested by playing a series of song pulses at a naturalistic volume, and measuring the physiological response by inserting tiny electrodes into their antennae. The fruit flies receiving the loud tone were found to have their hearing impaired relative to the control group.

When the flies were tested again a week later, those exposed to noise had recovered normal hearing levels. In addition, when the structure of the flies’ ears was examined in detail, the researchers discovered that nerve cells of the noise-rattled flies showed signs that they had been exposed to stress, including altered shapes of the mitochondria, which are responsible for generating most of a cell’s energy supply. Flies with a mutation making them susceptible to stress not only showed more severe reductions in hearing ability and more prominent changes in mitochondria shape, they still had deficits in hearing 7 days later, when normal flies had recovered.

The effect on the molecular underpinnings of the fruit fly’s ear are the same as experienced by humans, making the tests generally applicable to people, the researchers note.

“We found that fruit flies exhibit acoustic trauma effects resembling those found in vertebrates, including inducing metabolic stress in sensory cells,” Eberl says. “Our report is the first to report noise trauma in Drosophila and is a foundation for studying molecular and genetic conditions resulting from NIHL.”

“We hope eventually to use the system to look at how genetic pathways change in response to NIHL. Also, we would like to learn how the modification of genetic pathways might reduce the effects of noise trauma,” Christie adds.