A step forward in regenerating and repairing damaged nerve cells

A team of IRCM researchers, led by Dr. Frédéric Charron, recently uncovered a nerve cell’s internal clock, used during embryonic development. The discovery was made in collaboration with Dr. Alyson Fournier’s laboratory at the Montreal Neurological Institute. Published in the prestigious scientific journal Neuron, this breakthrough could lead to the development of new tools to repair and regenerate nerve cells following injuries to the central nervous system.

Researchers in Dr. Charron’s laboratory study neurons, which are the nerve cells that make up the central nervous system (brain and spinal cord). They want to better understand how neurons navigate through the developing embryo to arrive at their correct destination.

“To properly form neural circuits, developing axons (long extensions of neurons that form nerves) follow external signals to reach the right targets,” says Dr. Frédéric Charron, Director of the Molecular Biology of Neural Development research unit at the IRCM. “We discovered that nerve cells also have an internal clock, which changes their response to external signals as they develop over time.”

For this research project, IRCM scientists focused on the Sonic Hedgehog (Shh) protein, which gives cells important information for the embryo to develop properly and plays a critical role in the development of the central nervous system.

“It is known that axons follow the Shh signal during their development,” explains Dr. Patricia Yam, research associate in Dr. Charron’s laboratory and first author of the study. “However, axons change their behaviour once they reach this protein, and this has been a mystery for the scientific community. We found that a nerve cell’s internal clock switches its response to external signals when it reaches the Shh protein, at which time it becomes repelled by the Shh signal rather than following it.”

“Our findings therefore showed that more than one system is involved in directing axon pathfinding during development,” adds Dr. Yam. “Not only do nerve cells respond to external signals, but they also have an internal control system. This discovery is important because it offers new possibilities for developing techniques to regenerate and repair damaged nerve cells. Along with trying to modify external factors, we can now also consider modifying elements inside a cell in order to change its behaviour.”

Researchers define key events early in the process of cellular aging

For the first time, scientists at Fred Hutchinson Cancer Research Center have defined key events that take place early in the process of cellular aging.

Together the discoveries, made through a series of experiments in yeast, bring unprecedented clarity to the complex cascade of events that comprise the aging process and pave the way to understanding how genetics and environmental factors like diet interact to influence lifespan, aging and age-related diseases such as cancer and neurodegenerative disorders.

The findings, including unexpected results that link aspects of aging and lifespan to a mechanism cells use to store nutrients, are described in the Nov. 21 issue of Nature by co-authors Daniel Gottschling, Ph.D., a member of the Hutchinson Center’s Basic Sciences Division, and Adam Hughes, Ph.D., a postdoctoral fellow in the Gottschling Lab.

The work began with Hughes and Gottschling searching for the source of age-related damage in mitochondria.

“Normally, mitochondria are beautiful, long tubes, but as cells get older, the mitochondria become fragmented and chunky,” said Gottschling, also an affiliate professor in the Department of Genome Sciences at the University of Washington. “The changes in shape seen in aging yeast cells are also observed in certain human cells, such as neurons and pancreatic cells, and those changes have been associated with a number of age-related diseases in humans.”

What causes mitochondria to become distorted and dysfunctional as cells age had long been a mystery, but Gottschling and Hughes have discovered that specific changes in the vacuole lead directly to their malfunctioning.The researchers found the acidity of a structure in yeast cells known as the vacuole is critical to aging and the functioning of mitochondria – the power plants of the cell. They also describe a novel mechanism, which may have parallels in human cells, by which calorie restriction extends lifespan.

The Future of Memory: Remembering, Imagining, and the Brain

During the past few years, there has been a dramatic increase in research examining the role of memory in imagination and future thinking. This work has revealed striking similarities between remembering the past and imagining or simulating the future, including the finding that a common brain network underlies both memory and imagination. Here, we discuss a number of key points that have emerged during recent years, focusing in particular on the importance of distinguishing between temporal and nontemporal factors in analyses of memory and imagination, the nature of differences between remembering the past and imagining the future, the identification of component processes that comprise the default network supporting memory-based simulations, and the finding that this network can couple flexibly with other networks to support complex goal-directed simulations. This growing area of research has broadened our conception of memory by highlighting the many ways in which memory supports adaptive functioning.

Sophisticated worms
One cell does it all: Sensory input to motor output in extraordinary neuron

It’s one of the basic tenets of biological research — by studying simple “model” systems, researchers hope to gain insight into the workings of more complex organisms.

Caenorhabditis elegans — a tiny, translucent worm with just 302 neurons — has long been studied to understand how a nervous system is capable of translating sensory input into motion and behavior.

New research by the laboratory of Professor Aravi Samuel in the Harvard Physics Department and the Center for Brain Sciences, however, is uncovering surprising sophistication in the individual neurons of the worm’s “simple” nervous system.

Quan Wen, a postdoctoral fellow in the Samuel lab who spearheaded the research, has shown that a single type of neuron in the C. elegans nerve cord (the worm equivalent of the spinal cord) packs both sensory and motor capabilities. The locomotory systems of most creatures, including humans, use different neurons to gather sensory information about animal movement or to send signals to muscle cells. C. elegans encodes an entire sensorimotor loop into one particularly sophisticated type of motor neuron. The work is described in the journal Neuron.

“This type of circuit is completely new — this is not the way people think about any motor circuit,” Samuel said.

The discovery arose from researchers asking a simple question: How does C. elegans organize its movements?

“What sent us down this road was a phenomenon that we’ve observed in the lab,” Samuel explained. “If we place the worms in a wet environment, they will swim. On surfaces, however, they crawl. The question was how the animal ‘knew’ to do each. The answer had to be feedback: Something is telling the worm that it’s in a low-viscous environment here, and a high-viscous environment there.

“The general name for this is ‘proprioceptive feedback,’ ” Samuel continued. “It’s that process that allows your brain to understand what each of your legs is doing and coordinate your ability to walk, it gives you an awareness of your body posture. The real puzzle in this case, however, was that C. elegans has so few neurons … we didn’t understand how proprioceptive feedback could come back into the system.”

(Image credit: snickclunk)

Re-Timer ready to reset sleep

Today saw the launch of Re-Timer, a wearable green light device invented by Flinders University sleep researchers to reset the body’s internal clock.

The portable device, which is worn like a pair of sunglasses and emits a soft green light onto the eyes, will help to counter jet lag, keep shift workers more alert and get teenagers out of bed by advancing or delaying sleeping patterns.

Psychologist Professor Leon Lack, the device’s chief inventor, said that the light from Re-Timer stimulates the part of the brain responsible for regulating the 24-hour body clock.

The device has been designed with the benefit of 25 years of sleep research at Flinders University.

“Body clocks or circadian rhythms influence the timing of all our sleeping and waking patterns, alertness, performance levels and metabolism,” Professor Lack said.

“Photoreceptors in our eyes detect sunlight, signal our brain to be awake and alert, and set our rhythms accordingly. These rhythms vary regularly over a 24-hour cycle. However, this process is often impaired by staying indoors, traveling to other times zones, working irregular hours, or a lack of sunlight during winter months.

“Our extensive research studies have shown that green light is one of the most effective wavelengths for advancing or delaying the body clock, and to date is the only wearable device using green light.”

Professor Lack recommended wearing the glasses for three days for 50 minutes each day either after awakening in the morning to advance the body clock, or before bed for those wanting to delay the body clock to wake up later.

He said that Re-Timer’s light therapy offers a safer and, in many cases, more effective treatment for mistimed sleep than drug alternatives.

The device is being produced by local manufacturing firm SMR Components.

Glowing Vulcan ears reveal brain’s lost neurons

These glowing shapes aren’t the ears of a rave-happy Vulcan - they’re slices from a mouse’s brain.

The slice on the right is from a mouse that lacks a gene called Arl13b - the same gene whose mutation causes Joubert syndrome in humans. This is a rare neurological condition that is linked with autism-spectrum disorders and brain structure malformations.

Without Arl13b, the nerve cells known as interneurons can’t find the right destination in the cerebral cortex during the brain’s development. Since the interneurons don’t end up in the right places, they can’t be wired up properly later on. This causes the disrupted brain development, typical of Joubert syndrome, visible in the image on the right.

The researchers hope that their findings will lead to better treatments for people who have the syndrome. 

"Ultimately, if you’re going to come up with therapeutic solutions, it’s important to understand the biology of the disease," says Eva Anton of the University of North Carolina in Chapel Hill, who worked on the research, which was published in Developmental Cell last week.

Follow-up study finds lasting benefit from MDMA for people with PTSD

The follow-up study was based on an original trial held in 2010 where 20 patients suffering from long term PTSD were given MDMA (the main ingredient in the party drug ecstasy) as part of their psychotherapy sessions. The researchers reported at the time that 83% of the participants showed improvements in their condition two months later.

In this new work, the researchers revisited the original patients three and a half years later (one refused to participate leaving just 19) to see how well they were doing. They found that just two of the patients had suffered a relapse – the rest they say maintained the relief they had found in the original trial.

The research was sponsored by the group Multidisciplinary Association for Psychedelic Studies (MAPS), whose mission is to seek out treatments for a variety of mental ailments using non-traditional drug therapies. In addition to providing funds for the trials they also worked out agreements with the government to allow for legal testing of the drug (it currently has as a Schedule I status.)

Study leads Michael and Ann Mithoefer conducted the original trial out of their private practice office. Each trial was conducted with a single patient at a time and involved a non-pharmaceutical therapy session followed by one where the patient was given a dose of MDMA. Another traditional session was held later – the sessions that included use of the drug lasted up to eight hours because the effects of the drugs last that long.

The researchers believe that MDMA helps PTSD sufferers by allowing them to relive the emotionally traumatic experience that led to their condition in a more relaxed and receptive way. Because of the promising results, MAPS is calling on the government to relax its rules on the testing and use of MDMA for medical applications.

Brain waves encode rules for behavior

One of the biggest puzzles in neuroscience is how our brains encode thoughts, such as perceptions and memories, at the cellular level. Some evidence suggests that ensembles of neurons represent each unique piece of information, but no one knows just what these ensembles look like, or how they form.

A new study from researchers at MIT and Boston University (BU) sheds light on how neural ensembles form thoughts and support the flexibility to change one’s mind. The research team, led by Earl Miller, the Picower Professor of Neuroscience at MIT, identified groups of neurons that encode specific behavioral rules by oscillating in synchrony with each other.

The results suggest that the nature of conscious thought may be rhythmic, according to the researchers, who published their findings in the Nov. 21 issue of Neuron.

“As we talk, thoughts float in and out of our heads. Those are all ensembles forming and then reconfiguring to something else. It’s been a mystery how the brain does this,” says Miller, who is also a member of MIT’s Picower Institute for Learning and Memory. “That’s the fundamental problem that we’re talking about — the very nature of thought itself.”

An antidote for hypersomnia

Researchers at Emory University School of Medicine have discovered that dozens of adults with an elevated need for sleep have a substance in their cerebrospinal fluid that acts like a sleeping pill.

The results are scheduled for publication online Wednesday by the journal Science Translational Medicine.

Some members of this patient population appear to have a distinct, disabling sleep disorder called “primary hypersomnia,” which is separate from better-known conditions such as sleep apnea or narcolepsy. They regularly sleep more than 70 hours per week and have difficulties awakening. When awake, they still have reaction times comparable to someone who has been awake all night. Their sleepiness often interferes with work or school attendance, and conventional treatments such as stimulants bring little relief.

"These individuals report feeling as if they’re walking around in a fog — physically, but not mentally awake," says lead author David Rye, professor of neurology at Emory University School of Medicine and director of research for Emory Healthcare’s Program in Sleep. "When encountering excessive sleepiness in a patient, we typically think it’s caused by an impairment in the brain’s wake systems and treat it with stimulant medications. However, in these patients, the situation is more akin to attempting to drive a car with the parking brake engaged. Our thinking needs to shift from pushing the accelerator harder, to releasing the brake."

In a clinical study with seven patients who remained sleepy despite above-ordinary sleep amounts and treatment with stimulants, Emory researchers showed that treatment with the drug flumazenil can restore alertness, although flumazenil’s effectiveness was not uniform for all seven. Alertness was gauged through the psychomotor vigilance test, a measurement of reaction time.

Neural interaction in periods of silence

While in deep dreamless sleep, our hippocampus sends messages to our cortex and changes its plasticity, possibly transferring recently acquired knowledge to long-term memory. But how exactly is this done? Scientists from the Max Planck Institute for Biological Cybernetics have now developed a novel multimodal methodology called “neural event-triggered functional magnetic resonance imaging” (NET-fMRI) and presented the very first results obtained using it in experiments with both anesthetized and awake, behaving monkeys. The new methodology uses multiple-contact electrodes in combination with functional magnetic resonance imaging (fMRI) of the entire brain to map widespread networks of neurons that are activated by local, structure-specific neural events.