Scientists solve birth and migration mysteries of cortex’s powerful inhibitors, ‘chandelier’ cells

The cerebral cortex of the human brain has been called “the crowning achievement of evolution.” Ironically, it is so complex that even our greatest minds and most sophisticated science are only now beginning to understand how it organizes itself in early development, and how its many cell types function together as circuits.

A major step toward this great goal in neuroscience has been taken by a team led by Professor Z. Josh Huang, Ph.D., at Cold Spring Harbor Laboratory (CSHL). Today they publish research for the first time revealing the birth timing and embryonic origin of a critical class of inhibitory brain cells called chandelier cells, and tracing the specific paths they take during early development into the cerebral cortex of the mouse brain. 

These temporal and spatial sequences are regarded by Huang as genetically programmed aspects of brain development, accounting for aspects of the brain that are likely identical in every member of a given species, including humans. Exceptions to these stereotypical patterns include irregularities caused by gene mutations or protein malfunctions, both of which are now being identified in people with developmental disorders and neuropsychiatric illnesses.

Chandelier cells were first noticed only 40 years ago, and in the intervening years frustratingly little has been learned about them, beyond the fact that they “hang” individually among great crowds of excitatory cells in the cortex called pyramidal neurons, and that their relatively short branches make contact with these excitatory cells.  Indeed, a single chandelier cell connects, or “synapses,” with as many as 500 pyramidal neurons. Noting this, the great biologist Francis Crick decades ago speculated that chandelier cells exerted some kind of “veto” power over the messages being exchanged by the much more numerous excitatory cells in their vicinity.

Call that a ball? Dogs learn to associate words with objects differently than humans do

Previous studies have shown that humans between the ages of two to three typically learn to associate words with the shapes of objects, rather than their size or texture. For example, toddlers who learn what a ‘ball’ is and are then presented other objects with similar shapes, sizes or textures will identify a similarly-shaped object as ‘ball’, rather than one of the same size or texture.

Earlier research with dogs has shown that they can learn to associate words with categories of objects (such as ‘toy’), but whether their learning process was the same as that of humans was unknown.

In this new study, the scientists presented Gable, a five year old Border Collie, with similar choices to see if this ‘shape bias’ exists in dogs. They found that after a brief training period, Gable learned to associate the name of an object with its size, identifying other objects of similar size by the same name. After a longer period of exposure to both a name and an object, the dog learned to associate a word to other objects of similar textures, but not to objects of similar shape.

According to the authors, these results suggest that dogs (or at least Gable) process and associate words with objects in qualitatively different ways than humans do. They add that this may be due to differences in how evolutionary history has shaped human and dog senses of perceiving shape, texture or size.

Forget All-Night Studying, a Good Night’s Sleep Is Key to Doing Well on Exams

As fall semesters wind down at the country’s colleges and universities, students will be pulling all-night study sessions to prepare for final exams. Ironically, the loss of sleep during these all-nighters could actually work against them performing well, says a Harris Health System sleep specialist.

Dr. Philip Alapat, medical director, Harris Health Sleep Disorders Center, and assistant professor, Baylor College of Medicine, recommends students instead study throughout the semester, set up study sessions in the evening (the optimal time of alertness and concentration) and get at least 8 hours of sleep the night before exams.

“Memory recall and ability to maintain concentration are much improved when an individual is rested,” he says. “By preparing early and being able to better recall what you have studied, your ability to perform well on exams is increased.”

Alapat’s recommendations:
• Get 8-9 hours of sleep nightly (especially before final exams)

• Try to study during periods of optimal brain function (usually around 6-8 p.m.)

• Avoid studying in early afternoons, usually the time of least alertness

• Don’t overuse caffeinated drinks (caffeine remains in one’s system for 6-8 hours)

• Recognize that chronic sleep deprivation may contribute to development of long-term diseases like diabetes, high blood pressure and heart disease

If suffering from bouts of chronic sleep deprivation or nightly insomnia that lasts for more than a few weeks, Alapat suggests consulting a sleep specialist.

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.