olfactory-bulb

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“The smell of a walk”.

A man who was completely paralysed from the waist down can walk again after a British-funded surgical breakthrough which offers hope to millions of people who are disabled by spinal cord injuries.

Polish surgeons used nerve-supporting cells from the nose of Darek Fidyka, a Bulgarian man who was injured four years ago, to provide pathways along which the broken tissue was able to grow. The 38-year-old, who is believed to be the first person in the world to recover from complete severing of the spinal nerves, can now walk with a frame and has been able to resume an independent life, even to the extent of driving a car, while sensation has returned to his lower limbs.

The cells from the patient’s olfactory bulb in the brain were removed and grown in the lab. The olfactory bulb is on the inferior side of the brain and it transmits smell information from the nose to the brain, and is thus necessary for a proper sense of smell. The olfactory bulb is, with the subventricular zone, one of only two structures in the brain observed to undergo continuing neurogenesis in adult mammals. In most mammals, new neurons are born from neural stem cells in the sub-ventricular zone and migrate rostrally towards the main and accessory olfactory bulbs. 

The cells taken from the nasal cavity were injected into the spinal cord above and below the damaged site and strips of nerve fibres were taken from the patient’s ankle to form a bridge for the cells to grow across.

Professor Geoffrey Raisman, whose team at University College London’s institute of neurology discovered the technique, said: “We believe that this procedure is the breakthrough which, as it is further developed, will result in a historic change in the currently hopeless outlook for people disabled by spinal cord injury.” Raisman said he had never believed the “observed wisdom” that the central nervous system cannot regenerate damaged connections. He added: “Nerve fibres are trying to regenerate all the time. But there are two problems – crash barriers, which are scars, and a great big hole in the road. “In order for the nerve fibres to express that ability they’ve always had to repair themselves, first the scar has to be opened up, and then you have to provide a channel that will lead them where they need to go.”

He stressed that what had been achieved was a leap forward beyond promoting “plasticity” – the rewiring of remaining connections. The professor added: “The number of patients who are completely paralysed is enormous. There are millions of them in the world. “If we can convince the global neurosurgeon community that this works then it will develop very rapidly indeed.”

(To read more).

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Smell Turns Up in Unexpected Places

Smell is one of the oldest human faculties, yet it was one of the last to be understood by scientists. It was not until the early 1990s that biologists first described the inner workings of olfactory receptors — the chemical sensors in our noses — in a discovery that won a Nobel Prize.

Since then, the plot has thickened. Over the last decade or so, scientists have discovered that odor receptors are not solely confined to the nose, but found throughout body — in the liver, the heart, the kidneys and even sperm — where they play a pivotal role in a host of physiological functions.

Now, a team of biologists at Ruhr University Bochum in Germany has found that our skin is bristling with olfactory receptors. “More than 15 of the olfactory receptors that exist in the nose are also found in human skin cells,” said the lead researcher, Dr. Hanns Hatt. Not only that, but exposing one of these receptors (colorfully named OR2AT4) to a synthetic sandalwood odor known as Sandalore sets off a cascade of molecular signals that appears to induce healing in injured tissue.

In a series of human tests, skin abrasions healed 30 percent faster in the presence of Sandalore, a finding the scientists think could lead to cosmetic products for aging skin and to new treatments to promote recovery after physical trauma.

The presence of scent receptors outside the nose may seem odd at first, but as Dr. Hatt and others have observed, odor receptors are among the most evolutionarily ancient chemical sensors in the body, capable of detecting a multitude of compounds, not solely those drifting through the air.

“If you think of olfactory receptors as specialized chemical detectors, instead of as receptors in your nose that detect smell, then it makes a lot of sense for them to be in other places,” said Jennifer Pluznick, an assistant professor of physiology at Johns Hopkins University who in 2009 found that olfactory receptors help control metabolic function and regulate blood pressure in the kidneys of mice.

Think of olfactory receptors as a lock-and-key system, with an odor molecule the key to the receptor’s lock. Only certain molecules fit with certain receptors. When the right molecule comes along and alights on the matching receptor, it sets in motion an elaborate choreography of biochemical reactions. Inside the nose, this culminates in a nerve signal being sent to brain, which we perceive as odor. But the same apparatus can fulfill other biological functions as well.

Dr. Hatt was one of the first scientists to study these functions in detail. In a study published in 2003, he and his colleagues reported that olfactory receptors found inside the testes function as a kind of chemical guidance system that enables sperm cells to find their way toward an unfertilized egg, giving new meaning to the notion of sexual chemistry.

He has since identified olfactory receptors in several other organs, including the liver, heart, lungs, colon and brain. In fact, genetic evidence suggests that nearly every organ in the body contains olfactory receptors.

“I’ve been arguing for the importance of these receptors for years,” said Dr. Hatt, who calls himself an ambassador of smell, and whose favorite aromas are basil, thyme and rosemary. “It was a hard fight.”

But researchers have gradually awakened to the biological importance of these molecular sniffers and the promise they hold for the diagnosis and treatment of disease.

In 2009, for instance, Dr. Hatt and his team reported that exposing olfactory receptors in the human prostate to beta-ionone, a primary odor compound in violets and roses, appeared to inhibit the spread of prostate cancer cells by switching off errant genes.

The same year, Grace Pavlath, a biologist at Emory University, published a study on olfactory receptors in skeletal muscles. She found that bathing the receptors in Lyral, a synthetic fragrance redolent of lily of the valley, promoted the regeneration of muscle tissue. Blocking these receptors (by neutralizing the genes that code for them), on the other hand, was found to inhibit muscular regeneration, suggesting that odor receptors are a necessary component of the intricate biochemical signaling system that causes stem cells to morph into muscles cells and replace damaged tissue.

“This was totally unexpected,” Dr. Pavlath said. “When we were doing this, the idea that olfactory receptors were involved in tissue repair was not out there.” No doubt, few scientists ever imagined that a fragrance sold at perfume counters would possess any significant medical benefits.

But it may not be all that surprising. Olfactory receptors are the largest subset of G protein-coupled receptors, a family of proteins, found on the surface of cells, that allow the cells to sense what is going on around them. These receptors are a common target for drugs — 40 percent of all prescription drugs reach cells via GPCRs — and that augurs well for the potential of what might be called scent-based medicine.

But because of the complexity of the olfactory system, this potential may still be a long way off. Humans have about 350 different kinds of olfactory receptors, and that is on the low end for vertebrates. (Mice, and other animals that depend heavily on their sense of smell for finding food and evading predators, have more than 1,000.)

Despite recent advances, scientists have matched just a handful of these receptors to the specific chemical compounds they detect — an effort further complicated by the fact that many scent molecules may activate the same receptor and, conversely, multiple receptors often react to the same scent. Little is still known about what most of these receptors do — or, for that matter, how they ended up scattered throughout the body in the first place.

Nor is it even clear that olfactory receptors have their evolutionary origins in the nose. “They’re called olfactory receptors because we found them in the nose first,” said Yehuda Ben-Shahar, a biologist at Washington University in St. Louis who published a paper this year on olfactory receptors in the human lung, which he found act as a safety switch against poisonous compounds by causing the airways to constrict when we inhale noxious substances. “It’s an open question,” he said, “as to which evolved first.”

Camillo Golgi, Olfactory Bulb, 1875. “This 1875 drawing of a dog’s olfactory bulb by Camillo Golgi is but one of the many astonishing architectures that were revealed by a staining method that bears his name. Its application to the study of nervous tissue marks the beginning of modern neuroscience.” — Carl Schoonover, Portraits of the Mind: Visualizing the Brain from Antiquity to the 21st Century

Odor receptors discovered in lungs

Your nose is not the only organ in your body that can sense cigarette smoke wafting through the air. Scientists at Washington University in St. Louis and the University of Iowa have shown that your lungs have odor receptors as well.

Unlike the receptors in your nose, which are located in the membranes of nerve cells, the ones in your lungs are in the membranes of neuroendocrine cells. Instead of sending nerve impulses to your brain that allow it to “perceive” the acrid smell of a burning cigarette somewhere in the vicinity, they trigger the flask-shaped neuroendocrine cells to dump hormones that make your airways constrict.

The newly discovered class of cells expressing olfactory receptors in human airways, called pulmonary neuroendocrine cells, or PNECs, were found by a team led by Yehuda Ben-Shahar, PhD, assistant professor of biology, in Arts & Sciences, and of medicine at Washington University in St. Louis, and including colleagues Steven L. Brody, MD, and Michael J. Holtzman, MD, of the Washington University School of Medicine, and Michel J. Welsh, MD, of the University of Iowa Carver College of Medicine.

“We forget,” said Ben-Shahar, “that our body plan is a tube within a tube, so our lungs and our gut are open to the external environment. Although they’re inside us, they’re actually part of our external layer. So they constantly suffer environmental insults,” he said, “and it makes sense that we evolved mechanisms to protect ourselves.”

In other words, the PNECs, described in the March issue of the American Journal of Respiratory Cell and Molecular Biology, are sentinels, guards whose job it is to exclude irritating or toxic chemicals.

The cells might be responsible for the chemical hypersensitivity that characterizes respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Patients with these diseases are told to avoid traffic fumes, pungent odors, perfumes and similar irritants, which can trigger airway constriction and breathing difficulties.

The odor receptors on the cells might be a therapeutic target, Ben-Shahar suggests. By blocking them, it might be possible to prevent some attacks, allowing people to cut down on the use of steroids or bronchodilators.

Every breath you take
When a mammal inhales, volatile chemicals flow over two patches of specialized epithelial tissue high up in the nasal passages. These patches are rich in nerve cells with specialized odorant-binding molecules embedded in their membranes.

If a chemical docks on one of these receptors, the neuron fires, sending impulses along the olfactory nerve to the olfactory bulb in the brain, where the signal is integrated with those from hundreds of other similar cells to conjure the scent of old leather or dried lavender.

Aware that airway diseases are characterized by hypersensitivity to volatile stimuli, Ben-Shahar and his colleagues realized that the lungs, like the nose, must have some means of detecting inhaled chemicals.

Earlier, a team at the University of Iowa, where Ben-Shahar was a postdoctoral research associate, had searched for genes expressed by patches of tissue from lung transplant donors. They found a group of ciliated cells that express bitter taste receptors. When offending substances were detected, the cilia beat more strongly to sweep them out of the airway. This result was featured on the cover of the Aug. 28, 2009, issue of Science.

But since people are sensitive to many inhaled substances, not just bitter ones, Ben-Shahar decided to look again. This time he found that these tissues also express odor receptors, not on ciliated cells but instead on neuroendocrine cells, flask-shaped cells that dump serotonin and various neuropeptides when they are stimulated.

This made sense. “When people with airway disease have pathological responses to odors, they’re usually pretty fast and violent,” said Ben-Shahar. “Patients suddenly shut down and can’t breathe, and these cells may explain why.”

Ben-Shahar stresses the differences between chemosensation in the nose and in the lung. The cells in the nose are neurons, he points out, each with a narrowly tuned receptor, and their signals must be woven together in the brain to interpret our odor environment.

The cells in the airways are secretory, not neuronal, cells, and they may carry more than one receptor, so they are broadly tuned. Instead of sending nerve impulses to the brain, they flood local nerves and muscles with serotonin and neuropeptides. “They are possibly designed,” he said, “to elicit a rapid, physiological response if you inhale something that is bad for you.”

The different mechanisms explain why cognition plays a much stronger role in taste and smell than in coughing in response to an irritant. It is possible, for example, to develop a taste for beer. But nobody learns not to cough; the response is rapid and largely automatic.

The scientists suspect these pulmonary neuroscretory cells contribute to the hypersensitivity of patients with COPD to airborne irritants. COPD is a group of diseases, including emphysema, that is characterized by coughing, wheezing, shortness of breath and chest tightness.

When the scientists looked at the airway tissues from patients with COPD, they discovered that they had more of these neurosecretory cells than airway tissues from healthy donors.

Of mice and men
As a geneticist, Ben-Shahar would like to go farther, knocking out genes to make sure that the derangement of neurosecretory cells isn’t just correlated with airway diseases but instead suffices to produce it.

But there is a problem. “For example, a liver from a mouse and a liver from a human are pretty similar, they express the same types of cells. But the lungs from different mammalian species are often very different; you can see it at a glance,” Ben-Shahar said.

“Clearly, primates have evolved distinct cell lineages and signaling systems for respiratory-specific functions.”

This makes it challenging to unravel the biomolecular mechanisms of respiratory diseases. 

Still, he is hopeful that the PNEC pathways will provide targets for drugs that would better control asthma, COPD and other respiratory diseases. They would be welcome. There has been a steep rise in these diseases in the past few decades, treatment options have been limited, and there are no cures.

Figure 1. Reproduction of an original Cajal drawing from a Golgi stained horizontal section from 20-days-old mice, showing some morphological features of the accessory and main olfactory bulb. (A) Accessory olfactory bulb; (B) Main olfactory bulb; © Cortex; (D) Vomeronasal nerve; (a) Glomerular layer; (b) mitral/tufted layer; © Plane of the lateral olfactory tract; (d) granule cells [Ramon y Cajal (1901)].

Eduardo Martín-López et al. Postnatal characterization of cells in the accessory olfactory bulb of wild type and reeler mice; Front. Neuroanat., 22 May 2012

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Memory Accuracy and Strength Can Be Manipulated During Sleep

The sense of smell might seem intuitive, almost something you take for granted. But researchers from NYU Langone Medical Center have found that memory of specific odors depends on the ability of the brain to learn, process and recall accurately and effectively during slow-wave sleep — a deep sleep characterized by slow brain waves.

The sense of smell is one of the first things to fail in neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Indeed, down the road, if more can be learned from better understanding of how the brain processes odors, researchers believe it could lead to novel therapies that target specific neurons in the brain, perhaps enhancing memory consolidation and memory accuracy.

Reporting in the Journal of Neuroscience online April 9, researchers in the lab of Donald A. Wilson, PhD, a professor in the departments of Child and Adolescent Psychiatry and Neuroscience and Physiology at NYU Langone, and a research scientist at the NYU-affiliated Nathan Kline Institute for Psychiatric Research, showed in experiments with rats that odor memory was strengthened when odors sensed the previous day were replayed during sleep. Memories deepened more when odor reinforcement occurred during sleep than when rats were awake.

When the memory of a specific odor learned when the rats were awake was replayed during slow-wave sleep, they achieved a stronger memory for that odor the next day, compared to rats that received no replay, or only received replay when they were awake.

However, when the research team exposed the rats to replay during sleep of an odor pattern that they had not previously learned, the rats had false memories to many different odors. When the research team pharmacologically prevented neurons from communicating to each other during slow-wave sleep, the accuracy of memory of the odor was also impaired.

The rats were initially trained to recognize odors through conditioning. Using electrodes in the olfactory bulb, a part of the brain responsible for perceiving smells, the researchers stimulated different smell perceptions, according to precise patterns of electrical stimulation. Then, by replaying the patterns electrically, they were able to test the effects of slow-wave sleep manipulation.

Replay of learned electrical odors during slow-wave sleep enhanced the memory for those odors. When the learned smells were replayed while the rats were awake, the strength of the memory decreased. Finally, when a false pattern that the rat never learned was incorporated, the rats could not discriminate the smell accurately from the learned odor.

“Our findings confirm the importance of brain activity during sleep for both memory strength and accuracy,” says Dr. Wilson, the study’s senior author. “What we think is happening is that during slow-wave sleep, neurons in the brain communicate with each other, and in doing so, strengthen their connections, permitting storage of specific information.”

New Research on what the Nose ‘Knows’ Reveals an Unexpected Simplicity

Read the full article New Research on what the Nose ‘Knows’ Reveals an Unexpected Simplicity at NeuroscienceNews.com.

In rats, olfactory bulb neurons use simple ‘linear summation’ to make sense of fluctuating odor inputs from the surrounding environment.

The research in in Nature Neuroscience. (full access paywall)

Research: “Olfactory bulb coding of odors, mixtures and sniffs is a linear sum of odor time profiles” by Priyanka Gupta, Dinu F Albeanu and Upinder S Bhalla in Nature Neuroscience. doi:10.1038/nn.3913 (http://dx.doi.org/10.1038/nn.3913)

Image: The investigators discovered that two types of neuronal processors found in the rat olfactory bulb solve the difficult problem of identifying fluctuating environmental odors (which travel in plumes, depicted here) through linear summation. It’s an operation no less straightforward than the one a child uses to add or multiply numbers. Credit Albeanu Lab, CSHL.

Memory Accuracy and Strength Can Be Manipulated During Sleep

The sense of smell might seem intuitive, almost something you take for granted. But researchers from NYU Langone Medical Center have found that memory of specific odors depends on the ability of the brain to learn, process and recall accurately and effectively during slow-wave sleep — a deep sleep characterized by slow brain waves.

The sense of smell is one of the first things to fail in neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Indeed, down the road, if more can be learned from better understanding of how the brain processes odors, researchers believe it could lead to novel therapies that target specific neurons in the brain, perhaps enhancing memory consolidation and memory accuracy.

Reporting in the Journal of Neuroscience online April 9, researchers in the lab of Donald A. Wilson, PhD, a professor in the departments of Child and Adolescent Psychiatry and Neuroscience and Physiology at NYU Langone, and a research scientist at the NYU-affiliated Nathan Kline Institute for Psychiatric Research, showed in experiments with rats that odor memory was strengthened when odors sensed the previous day were replayed during sleep. Memories deepened more when odor reinforcement occurred during sleep than when rats were awake.

When the memory of a specific odor learned when the rats were awake was replayed during slow-wave sleep, they achieved a stronger memory for that odor the next day, compared to rats that received no replay, or only received replay when they were awake.

However, when the research team exposed the rats to replay during sleep of an odor pattern that they had not previously learned, the rats had false memories to many different odors. When the research team pharmacologically prevented neurons from communicating to each other during slow-wave sleep, the accuracy of memory of the odor was also impaired.

The rats were initially trained to recognize odors through conditioning. Using electrodes in the olfactory bulb, a part of the brain responsible for perceiving smells, the researchers stimulated different smell perceptions, according to precise patterns of electrical stimulation. Then, by replaying the patterns electrically, they were able to test the effects of slow-wave sleep manipulation.

Replay of learned electrical odors during slow-wave sleep enhanced the memory for those odors. When the learned smells were replayed while the rats were awake, the strength of the memory decreased. Finally, when a false pattern that the rat never learned was incorporated, the rats could not discriminate the smell accurately from the learned odor.

“Our findings confirm the importance of brain activity during sleep for both memory strength and accuracy,” says Dr. Wilson, the study’s senior author. “What we think is happening is that during slow-wave sleep, neurons in the brain communicate with each other, and in doing so, strengthen their connections, permitting storage of specific information.”

Dr. Wilson says these findings are the first to demonstrate that memory accuracy, not just memory strength, is altered during short-wave sleep. In future research, Dr. Wilson and his team hope to examine how sleep disorders affect memory and perception.

Smells Shape the Brain

The olfactory bulb — the brain structure that receives smell input from the nose — changes substantially over the course of early development. This image shows how the olfactory bulbs of the zebrafish Danio rerio grow in both size and complexity (from the youngest at top to oldest at bottom).

The spherical structures that appear in red, called glomeruli, receive input from nerve fibers that carry information about smells. Scientists found out that while some of these glomeruli remained relatively unchanged over the course of early development, others emerged and developed in response to different scents. This discovery is providing new insight into how experiences can physically affect the development of sensory systems.

Beautiful Image.

Credit: Braubach, et al. The Journal of Neuroscience, 2013.

Scientists Sniff Out Unexpected Role for Stem Cells in the Brain

Read the full article Scientists Sniff Out Unexpected Role for Stem Cells in the Brain at NeuroscienceNews.com.

NIH scientists find that restocking new cells in the brain’s center for smell maintains crucial circuitry.

The research is in Journal of Neuroscience. (full access paywall)

Research: “Adult Neurogenesis Is Necessary to Refine and Maintain Circuit Specificity” by Diana M. Cummings, Jason S. Snyder, Michelle Brewer, Heather A. Cameron, and Leonardo Belluscio in Journal of Neuroscience. doi:10.1523/JNEUROSCI.2463-14.2014

Image: Adult-born cells travel through the thin rostral migratory stream before settling into the olfactory bulb, the large structure in the upper right of the image. Credit Belluscio Lab, NINDS.

Sugar solution makes tissues see-through

Japanese researchers have developed a new sugar and water-based solution that turns tissues transparent in just three days, without disrupting the shape and chemical nature of the samples. Combined with fluorescence microscopy, this technique enabled them to obtain detailed images of a mouse brain at an unprecedented resolution.

The team from the RIKEN Center for Developmental biology reports their finding today in Nature Neuroscience.

Over the past few years, teams in the USA and Japan have reported a number of techniques to make biological samples transparent, that have enabled researchers to look deep down into biological structures like the brain.

“However, these clearing techniques have limitations because they induce chemical and morphological damage to the sample and require time-consuming procedures,” explains Dr. Takeshi Imai, who led the study.

SeeDB, an aqueous fructose solution that Dr. Imai developed with colleagues Drs. Meng-Tsen Ke and Satoshi Fujimoto, overcomes these limitations.

Using SeeDB, the researchers were able to make mouse embryos and brains transparent in just three days, without damaging the fine structures of the samples, or the fluorescent dyes they had injected in them.

They could then visualize the neuronal circuitry inside a mouse brain, at the whole-brain scale, under a customized fluorescence microscope without making mechanical sections through the brain.

They describe the detailed wiring patterns of commissural fibers connecting the right and left hemispheres of the cerebral cortex, in three dimensions, for the first time. They also report that they were able to visualize in three dimensions the wiring of mitral cells in the olfactory bulb, which is involved the detection of smells, at single-fiber resolution.

“Because SeeDB is inexpensive, quick, easy and safe to use, and requires no special equipment, it will prove useful for a broad range of studies, including the study of neuronal circuits in human samples,” explain the authors.

For decades, scientists didn’t believe that adult brains could replenish themselves with neurons. Recent research has shown that adult-born neuroprogenitor cells do exist and a new study in the Journal of Neuroscience shows that newly formed brain cells in the olfactory system of mice help to maintain connections between neurons. When researchers at the National Institutes of Health prevented the formation of new olfactory neurons in adult mice, the brain circuitry in the olfactory region began to break down. When the cells were allowed to divide as normal, they traveled through a thin rostral migratory stream before arriving in the olfactory bulb (pictured, upper right). The researchers are currently testing whether neurogenesis in other brain regions, such as the hippocampus, has a similar function.

Read more: http://bit.ly/1sO7eGQ
Journal article: Adult Neurogenesis Is Necessary to Refine and Maintain Circuit Specificity. Journal of Neuroscience, 2014. doi:10.1523/JNEUROSCI.2463-14.2014

Researchers observe stem cell specialization in the brain

Adult stem cells are flexible and can transform themselves into a wide variety of special cell types. Because they are harvested from adult organisms, there are no ethical objections to their use, and they therefore open up major possibilities in biomedicine. For instance, adult stem cells enable the stabilization or even regeneration of damaged tissue. Neural stem cells form a reservoir for nerve cells. Researchers hope to use them to treat neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. Tübingen researchers led by Professor Olga Garaschuk of the University of Tübingen’s Institute for Physiology, working with colleagues from Yale University, the Max Planck Institute of Neurobiology in Martinsried and the Helmholtz Center in Munich, studied the integration of these cells into the pre-existing neural network in the living organism. The results of their study have been published in the latest edition of Nature Communications.

There are only two places in the brains of adult mammals where stem cells can be found – the lateral ventricles and the hippocampus. These stem cells are generating neurons throughout life. The researchers focused on a stem cell zone in the lateral ventricle, from where progenitors of the nerve cells migrate towards the olfactory bulb. The olfactory nerves which start in the nasal tissue run down to this structure, which in mice is located at the frontal base of the brain. It is there that the former stem cells specialized in the task of processing information on smells detected by the nose. “Using the latest methods in microscopy, we were for the first time able to directly monitor functional properties of migrating neural progenitor cells inside the olfactory bulb in mice,” says Olga Garaschuk. The researchers were able to track the cells using special fluorescent markers whose intensity changes according to the cell’s activity.

The study showed that as little as 48 hours after the cells had arrived in the olfactory bulb, around half of them were capable of responding to olfactory stimuli. Even though the neural progenitor cells were still migrating, their sensitivity to odorants and their electrical activity were similar to those of the surrounding, mature neurons. The mature pattern of odor-evoked responses of these cells strongly contrasted with their molecular phenotype which was typical of immature, migrating neuroblasts. “Our data reveal a remarkably rapid functional integration of adult-born cells into the pre-existing neural network,” says Garaschuk, “and they show that sensory-driven activity is in a position to orchestrate their migration and differentiation as well as their decision of when and where to integrate.”

Research reveals first glimpse of a brain circuit that helps experience to shape perception

Odors have a way of connecting us with moments buried deep in our past. Maybe it is a whiff of your grandmother’s perfume that transports you back decades. With that single breath, you are suddenly in her living room, listening as the adults banter about politics. The experiences that we accumulate throughout life build expectations that are associated with different scents. These expectations are known to influence how the brain uses and stores sensory information. But researchers have long wondered how the process works in reverse: how do our memories shape the way sensory information is collected?

In work published today in Nature Neuroscience, scientists from Cold Spring Harbor Laboratory (CSHL) demonstrate for the first time a way to observe this process in awake animals. The team, led by Assistant Professor Stephen Shea, was able to measure the activity of a group of inhibitory neurons that links the odor-sensing area of the brain with brain areas responsible for thought and cognition. This connection provides feedback so that memories and experiences can alter the way smells are interpreted. 

The inhibitory neurons that forget the link are known as granule cells. They are found in the core of the olfactory bulb, the area of the mouse brain responsible for receiving odor information from the nose. Granule cells in the olfactory bulb receive inputs from areas deep within the brain involved in memory formation and cognition. Despite their importance, it has been almost impossible to collect information about how granule cells function. They are extremely small and, in the past, scientists have only been able to measure their activity in anesthetized animals. But the animal must be awake and conscious in order to for experiences to alter sensory interpretation. Shea worked with lead authors on the study, Brittany Cazakoff, graduate student in CSHL’s Watson School of Biological Sciences, and Billy Lau, Ph.D., a postdoctoral fellow. They engineered a system to observe granule cells for the first time in awake animals. 

Granule cells relay the information they receive from neurons involved in memory and cognition back to the olfactory bulb. There, the granule cells inhibit the neurons that receive sensory inputs. In this way, “the granule cells provide a way for the brain to ‘talk’ to the sensory information as it comes in,” explains Shea. “You can think of these cells as conduits which allow experiences to shape incoming data.”

Why might an animal want to inhibit or block out specific parts of a stimulus, like an odor? Every scent is made up of hundreds of different chemicals, and “granule cells might help animals to emphasize the important components of complex mixtures,” says Shea. For example, an animal might have learned through experience to associate a particular scent, such as a predator’s urine, with danger. But each encounter with the smell is likely to be different. Maybe it is mixed with the smell of pine on one occasion and seawater on another. Granule cells provide the brain with an opportunity to filter away the less important odors and to focus sensory neurons only on the salient part of the stimulus. 

Now that it is possible to measure the activity of granule cells in awake animals, Shea and his team are eager to look at how sensory information changes when the expectations and memories associated with an odor change. “The interplay between a stimulus and our expectations is truly the merger of ourselves with the world. It exciting to see just how the brain mediates that interaction,” says Shea.

margieargie asked:

Jade/Terezi, 12

“Jade, that is hideous.”

“No! It’s awesome!”

Terezi wrinkles her nose. “Your definition of ‘awesome’ leaves much to be desired.”

“Aww, come on! Live a little!” Jade wiggles the tie-dyed Squiddle closer to the troll’s face as she leans forward.

“If living a little means sacrificing my olfactory bulbs, I’ll pass. It smells like a giant fly lusus died in a refuse pile.”

“Really?” Jade sniffs the plush abomination experimentally. “It just smells like synthetic fiber and cheap dye to me. I thought you liked bright col-”

Faster than an eye-blink, the human finds herself pinned by a wickedly grinning troll.

“I do!” Terezi presses a quick kiss to Jade’s nose.

“Hey! You’re supposed to be an honest legislacerator!” she protests through a giggle.

“I am,” sharp teeth glitter behind black lips. “Honest legislacerators lie all the time. Truth! Your crazy colored Squiddle is actually very awesome, Jade.”

The Origin, Development and Molecular Diversity of Rodent Olfactory Bulb Glutamatergic Neurons Distinguished by Expression of Transcription Factor NeuroD1.

PubMed: The Origin, Development and Molecular Diversity of Rodent Olfactory Bulb Glutamatergic Neurons Distinguished by Expression of Transcription Factor NeuroD1.

PLoS One. 2015;10(6):e0128035

Authors: Roybon L, Mastracci TL, Li J, Stott SR, Leiter AB, Sussel L, Brundin P, Li JY

Abstract
Production of olfactory bulb neurons occurs continuously in the rodent brain. Little is known, however, about cellular diversity in the glutamatergic neuron subpopulation. In the central nervous system, the basic helix-loop-helix transcription factor NeuroD1 (ND1) is commonly associated with glutamatergic neuron development. In this study, we utilized ND1 to identify the different subpopulations of olfactory bulb glutamategic neurons and their progenitors, both in the embryo and postnatally. Using knock-in mice, transgenic mice and retroviral transgene delivery, we demonstrate the existence of several different populations of glutamatergic olfactory bulb neurons, the progenitors of which are ND1+ and ND1- lineage-restricted, and are temporally and regionally separated. We show that the first olfactory bulb glutamatergic neurons produced - the mitral cells - can be divided into molecularly diverse subpopulations. Our findings illustrate the complexity of neuronal diversity in the olfactory bulb and that seemingly homogenous neuronal populations can consist of multiple subpopulations with unique molecular signatures of transcription factors and expressing neuronal subtype-specific markers.

PMID: 26030886 [PubMed - as supplied by publisher] http://dlvr.it/B43nK6