New role of adenosine in the regulation of REM sleep discovered

The regulation and function of sleep is one of the biggest black boxes of today’s brain science. A new paper published online on August 2 in the journal Brain Structure & Function finds that rapid eye movement (REM) sleep is suppressed by adenosine acting on a specific subtype of adenosine receptors, the A2A receptors, in the olfactory bulb. The study was conducted by researchers at Fudan University’s School of Basic Medical Sciences in the Department of Pharmacology and the University of Tsukuba’s International Institute for Integrative Sleep Medicine (WPI-IIIS). The research team used pharmacological and genetic methods to show that blocking A2A receptors or neurons that contain the A2A receptors in the olfactory bulb increases REM sleep in rodents.

Adenosine has long been known to represent a state of relative energy deficiency and to induce sleep by blocking wakefulness. The new findings demonstrate for the first time that adenosine also inhibits REM sleep, a unique phase of sleep in mammalians that is characterized by random eye movement and low muscle tone throughout the body. The Chinese-Japanese research team discovered that adenosine acts specifically in the olfactory bulb which transmits odor information from the nose to the brain. Because olfactory dysfunction can be treated with an A2A receptor antagonist, for example caffeine, it is possible that REM sleep and the perception of odors are linked in the olfactory bulb. Interestingly, the ability to smell is reduced in patients with REM sleep behavior disorder (RBD). Dreams which mostly occur during REM sleep are usually a pure mental activity while the body is at rest. However, patients who suffer from RBD act out their dreams.

Yiqun Wang, the lead investigator on this project said that “our findings encourage us to believe that A2A receptors may be a novel target to treat RBD by suppressing REM sleep. Our observation clearly suggest an intriguing possibility for treating this disease with an A2A receptor agonist or allosteric modulator.”

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

3 Fun Facts About Your Canine Companions

Happy National Dog Day, y’all! We thought we’d throw around some pup-appreciation with the following dog olfactory facts for you to fetch. 

1. Besides being much more powerful than ours, a dog’s sense of smell can pick up things that can’t even be seen at all. The olfactory bulb, the area dedicated to processing smells, takes up many times more relative brain area in dogs than humans. This allows dogs to distinguish and remember a staggering variety of specific scents.

2. Everything in the street, every passing person or car, any contents of the neighbor’s trash, each type of tree, and all the birds and insects in it has a distinct odor profile telling your dog what it is, where it is, and which direction it’s moving in.

3. Dogs smell in stereo. The ability to smell separately - with each nostril - helps them determine from what direction smells come. A whole separate olfactory system, called the vomeronasal organ, above the roof of the mouth, detects the hormones all animals, including humans, naturally release.

For more on how dogs smell, check out the TED-Ed Lesson How do dogs “see” with their noses? - Alexandra Horowitz 

Animation by provinciastudio

Smells Dangerous

Milk, toothpaste, coffee, petrol, spices, flowers – all smells you may have recognised today. Each one releases a different set of chemicals into the air which trigger sensitive cells in the olfactory bulb (just behind the nose). Generally we recognise smells as a blend of signals from these cells, combined by the brain into a ‘flowery’ or 'toothpastey’ smell. Pictured in bright colours in a mouse, cells in the olfactory necklace work differently. Each cell senses entire sets of smelly chemicals at once – and humans have them, too. Researchers think necklace cells respond to overall smells, saving the brain time in assembling the smell from other olfactory cells. Which smells might be this important, though? Perhaps those we associate with danger, or pheromones released by a potential mate – future studies in the brain will hopefully solve this smelly mystery.

Written by John Ankers

You can also follow BPoD on Twitter and Facebook

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.

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

Cranial Nerves

Nerves supplying the body can be divided in to cranial and spinal. Cranial nerves emerge from the brain or brain stem and spinal from the spinal chord. There are 12 pairs of cranial nerves. They are components of the peripheral nervous system, with the exception of the optic nerve, as their axons extend beyond the brain to supply other parts of the body. They are named numerically from region of the nose (rostral) to back of the head (caudal). Here’s a brief overview of all twelve nerves and their basic functions.

I – The Olfactory Nerve. The cells of this nerve arise from the olfactory membrane of the nasal mucosa. The dendrites of the nerve cells project in to the olfactory mucosa. The axons of these cells combine to form the olfactory nerve. They join the brain at the olfactory bulb, located at the end nearest the nose. The fibres are short and lie deep and protected from casual injury. It is often found that loss or interference of sense of smell is due to blockage of the air passage leading to the olfactory mucosa, not due to nerve damage.

II – The Optic Nerve. This nerve connects the retina to the diencephalon of the brain. It is the only cranial nerve considered to be part of the central nervous system. This means the fibres are incapable of regeneration, hence why damage to the optic nerve produces irreversible blindness. Interestingly the eye's blind spot is a result of the absence of photoreceptor cells in the area of the retina where the optic nerve leaves the eye. I find the optic nerves easy to spot when looking at the brain from below as they form the optic chiasm. This is the point at which they cross and forms a clear ‘x’.

III- The Oculomotor Nerve. This nerve controls most of the eye’s movements including the constriction of the pupil and levitation of the eyelid. Damage to the nerve can cause double vision and inability to open the eye. A symptom of damage to this nerve is tilting of the head.

IV – The Trochlear Nerve. This nerve is a small somatic motor nerve and innervates the dorsal oblique muscle of the eye, responsible for allowing the eye to look down and up as well as internal rotations. Damage to the nerve can cause one eye to drift upwards in relation to the undamaged eye, meaning patients tilt their heads down to compensate.

V – The Trigeminal Nerve. This is the largest cranial nerve and is so called as it has three major divisions. It is sensory to the skin and deeper tissue of the face and motor to certain facial muscles, playing a large role in mastication.

VI – The Abducent Nerve. This nerve controls the movement of the lateral rectus muscle of the eye. It also plays a role in eye retraction for protection. Injury produces the inability to deviate the eyeball away from the midline of the body.

VII – The Facial Nerve. This nerve innervates the muscles of facial expression. It also functions in the conveyance of taste sensations from the front two thirds of the tongue. As well as this it can increase saliva flow through certain salivary glands.

VIII – The Vestibulocochlear Nerve. This nerve is named after the vestibular and cochlear components of the inner ear. It transmits information on sound and balance. Damage can lead to deafness, impaired balance and dizziness.

IX – The Glossopharyngeal Nerve. This nerve has any roles including the innervation of certain muscles of the palate of the mouth, certain salivary glands and the sensory mucosa of the root of the tongue, palate and pharynx. Damage can lead to difficulty swallowing as well as the loss of ability to taste bitter and sour things in humans.

X – The Vagus Nerve. This is a very important nerve and one frequently discussed when considering many important systems within the body. It is the longest of all cranial nerves and extends to supply the pancreas, spleen, kidneys, adrenals, and intestine. It has parasympathetic control of the heart and digestive tract as well as certain glands and involuntary muscles.

XI – The Accessory Nerve. This plays a role in neck turning and elevation of the scapula (shoulder). Muscle atrophy of the shoulder region indicates damage to this nerve.

XII – The Hypoglossal Nerve. This nerve’s name relates to the fact that is runs under the tongue, innervating the tongue’s internal and external musculature. It has important roles in speech, food manipulation and swallowing.

The first illustration by Camillo Golgi showing a network of neurons found in the olfactory bulb of a dog. Golgi has invented a method, now called Golgi-stain, which is used to image neurons in different tissues. Golgi-stain is based on reaction between potassium dichromate and silver nitrate, which leads to silver chromate being deposited on cell membranes and giving them dark colour. Only random and relatively few neurons are stained at a time, allowing to distinguish single cells, which are part of dense and complicated neuronal networks. Golgi has described his technique in 1873 and it provided one of the strongest evidence at that time to prove that neurons are the building blocks of the nervous system. Golgi, together with Santiago Ramón y Cajal, was awarded the Nobel Prize in 1906 in recognition of their work on the structure of the nervous system”.

Image source

MYTH: Once your brain cells die, they can’t grow back. The brain does not change.

This follows the myth that you are born with all the neurons you’ll ever have. In fact, some neurons do regenerate and/or change. If they couldn’t, you’d have lost your sense of smell years ago! Not to mention, you’d never be able to form new memories or learn new things.

In the neuroscience community, we often discuss this with terms like “neurogenesis” and brain “plasticity.” Meaning that new neurons can grow (neurogenesis) and can change (plasticity) with time. Adult neurogenesis in mammals appears to occur in the olfactory bulb (these neurons have frequent turnover, due to their exposure and death) and the hippocampus- the part of the brain that creates memories (more info here). There is evidence that it may happen elsewhere in the brain too (for instance, this paper in Cell showed that it happens to interneurons in striatum).

However, unfortunately, some nerves can’t repair themselves or regrow once damaged in adulthood (like those in the spinal column). Not all neurons are like this, and sometimes they can repair themselves with partial damage but not when completely damaged, as comes into play with paralysis and Alzheimer’s disease. The field is still learning about these and which factors make them irreparable or irreplaceable. Maybe one day we’ll be able to fix all neural damage (people are investigating how to do this now! We’re not close to a cure, but others are beginning to understand this better).

For now, it’s important to know that this absolute statement is a myth, and some neurons do regrow- and our brain is changing all the time, as we learn new things and experience new memories.

[Image Source]


ALS-linked gene found switched on in new bits of the brain

ALS, also known as Motor Neuron Disease, is a fatal neurodegenerative condition for which we don’t have a cure and don’t fully understand.

We do know that a gene called C9orf72 is often involved, and many patients have abnormal repeated sequences within the gene causing neurons in the brain to die. The gene is also implicated in a type of dementia called Frontotemporal Dementia (FTD).

Now scientists studying it in mouse brains have found it is switched on in two regions that we didn’t know about before. 

They discovered that C9orf72 is strongly expressed in the hippocampus -  containing adult stem cells and which is important for memory - and the olfactory bulb - which is involved in the sense of smell. 

Loss of smell is sometimes a symptom in FTD.

The University of Bath team hope the findings will help researchers gain a better understanding of  C9orf72 ′s role in both diseases and help map where it is switched on and off as the brain develops. 

This could help us figure out new ways to slow down, treat or even cure the symptoms and explain why people born with abnormalities in  C9orf72 don’t develop symptoms until decades after birth. 

Read the paper

Images:  Andrew L Bashford and Vasanta Subramanian

The top and bottom images show mouse cerebellum stained to reveal the Purkinje neurons (green).

The middle image shows the dentate gyrus of the mouse hippocampal formation, which contributes to the formation of new memories stained for neurons (green) and stem cells (red).

(Image caption: In light brown, in the center of the image, a new adult-born neuron. The neurons in blue are synaptic partner neurons, which connect to the new neurons. The neurons in dark brown are pre-existing neurons. Credit: © Institut Pasteur/PM Lledo)

The relentless dynamism of the adult brain

Although most neurons are generated during embryogenesis, some regions of the brain, such as the olfactory bulb in rodents and the hippocampus in humans, are capable of constantly regenerating their neurons in adulthood. Scientists first conclusively discovered these new adult neurons around 15 years ago, but their function remained a mystery, mainly because they are inaccessible in living animals.

In an article published in the journal Neuron, scientists from the Laboratory for Perception and Memory at the Institut Pasteur directed by CNRS scientist Pierre-Marie Lledo provide further evidence of the highly dynamic nature of the changes observed at the neuronal level in adult brains. The scientists spent several months observing the development of neurons formed in adulthood in the olfactory bulbs of mice. This gave them the unique opportunity to see the formation, stabilization and elimination of connections between neurons in real time.

They revealed that in the olfactory bulb, where new neurons are continuously formed, the connections between these new neurons and neighboring cells are significantly rearranged throughout their lifetime. All these neurons are constantly reorganizing the billions of “synaptic” contacts they establish among themselves. The scientists were surprised by this observation. “We expected to see the synapses gradually stabilizing, as happens during brain development. But astonishingly, these synapses proved to be highly dynamic throughout the life of the new neurons. Also, these dynamics were reflected in the principal neurons, their primary synaptic partner,” explained first author, Kurt Sailor, from the Institut Pasteur.

To observe the ongoing formation of neuronal circuits, the scientists marked the new neurons with a green fluorescent protein (GFP), to allow imaging of the dynamic changes with microscopy. These experiments were carried out over a period of several months to follow the entire life cycle of the new neurons. In the first three weeks of their life, these new neurons extended their cellular projections, known as dendrites, to form several ramifications, which subsequently became very stable. They next observed the neuronal spines, the structure where synapses form, and demonstrated that 20% of the synapses between new and pre-existing neurons were changed on a daily basis – a phenomenon that was also observed in their synaptic partners, the principal olfactory bulb neurons. Using computer-based models, the authors showed that these dynamics enabled the synaptic network to adjust efficiently and reliably to ongoing sensory changes in the environment.

“Our findings suggest that the plasticity of this constantly regenerating region of the brain occurs with continuous physical formation and elimination of synaptic connections. This structural plasticity reveals a unique dynamic mechanism that is vital for the regeneration and integration of new neurons within the adult brain circuit,” concluded the scientists. More generally, this study suggests a universal plasticity mechanism in brain regions that are closely associated with memory and learning.

Robert T. Hatt - The Evolving Brain, “Guide to the Biology of Mammals”, 1933.

From fish to man the brain increases in complexity and in the size of certain parts, especially the forebrain. In the lower forms the forebrain functions chiefly in connection with the ‘olfactory bulbs’ and smelling nerves. In the mammals, the upper part of the forebrain becomes differentiated as the neopallium, or new brain, gradually assumes control and finally becomes greatly convoluted or infolded, largely concealing, especially in the side and top views of the older parts of the brain.  

What You Need to Know About Buying Essential Oils

By Amanda Abella 

Aromatherapy is the therapeutic use of essential oils from plants for the improvement of a person’s overall well being. This alternative form of treatment has become so popular that even organizations like the National Cancer Institute have entire webpages dedicated to the uses of essential oils.

The effects of Aromatherapy are theorized to be a result of the binding of chemicals in the essential oils to the olfactory bulb, the neural structure in the vertebrae forebrain involved with our sense of smell. This binding directly affects the brain’s emotional center, the limbic system. Some essential oils are also said to have antibacterial and anti-fungal properties.

While many use essential oils as a form of therapy, it’s uses have also caused some controversy. Just recently the FDA issued warning letters to two major essential oil companies, Young Living and DoTerra, citing that they are selling products which claim to help with health concerns without the approval of the FDA. This is interesting to note because essentials oils can be regulated as either drugs (heavily regulated) or cosmetics (not so heavily regulated) depending on the company . Usually it’s the latter.

Since essential oils are typically regulated as cosmetics, and since cosmetics are the least regulated form of consumer products by the FDA, that means there are a lot of essential oils on the market that could potentially have harmful chemicals. Use our guide below to get clear on what you need to know about purchasing essential oils.

Keep reading

These popular facts commonly believed to be true are in fact bullshit

Myth: You swallow 8 spiders a year.
Fact: It was thought up by PC Professional columnist named Lisa Holst to show that you can make up anything on the Internet.

Myth:Your fingernails and toenails continue to grow even after your death.
Fact: They appear to grow because your skin surrounding them shrinks, giving an illusion that they are growing.

Myth: If you touch a baby bird, its mother will abandon it(our scent would cause their parents to reject and abandon them).
Fact: Birds will not readily abandon their young because they “smell humans.” For one thing, birds don’t have a great sense of smell. Their olfactory bulbs are small and simple compared to other animals.

Myth: During a nose bleed, tilt your head back to help stop the bleeding.
Fact: All this does is make the blood run down your throat. Just because blood is no longer visibly leaking from your nose does not mean that you are no longer loosing blood, only that gravity has diverted the blood in to an even more inconvenient direction.

Myth:You only use 5-10% of your brain.
Facts: In reality, the 10 percent claim is 100 percent myth. You use all of your brain. The only instances where there are unused regions of the brain are those in which brain damage or disease has destroyed certain regions.

Myth: The number of people alive today is greater than the number of people who have ever died.
Fact: BBC News spoke to the Population Reference Bureau in Washington DC, and they estimate that about 107 billion people have been born since humanity first emerged, which they set 50,000 years ago.

Myth: Cracking your knuckles doesn’t give you arthritis.
Fact: Cracking your knuckles may aggravate the people around you, but it probably won’t raise your risk for arthritis. That’s the conclusion of several studies that compared rates of hand arthritis among habitual knuckle-crackers and people who didn’t crack their knuckles.

Myth: NASA spent millions developing a pen that worked in zero-gravity, where soviet cosmonauts used pencils.
Fact: Originally, NASA astronauts, like the Soviet cosmonauts, used pencils, according to NASA historians. In fact, NASA ordered 34 mechanical pencils from Houston’s Tycam Engineering Manufacturing, Inc., in 1965. They paid $4,382.50 or $128.89 per pencil. When these prices became public, there was an outcry and NASA scrambled to find something cheaper for the astronauts to use.

Myth: You will burn the same number of calories walking a mile as you will running a mile
Fact: In fact you burn more calories in running 1mile rather than walking same distance.(read more here)

Myth: Your fingers wrinkle when they’re wet because they absorb water.
Fact: Research based theory: pruney fingers are an adaptation to help humans, and probably other primates, get a better grip during wet conditions.

more facts?


Visualising a hormone that helps us remember

Mike Ludwig and his team from the University of Edinburgh have discovered nerve cells which release a hormone that helps us recognise and remember new people.

In the images above, the nerve cells (green) are expressing vasopressin – the hormone involved in this memory. These nerve cells are located in part of the brain known as the olfactory bulb, an area that helps us to process and perceive different smells. Our sense of smell is closely linked to memory and plays a vital role in recognition not only in people, but in other mammals too.

After Mike and his colleagues discovered that the vasopressin is expressed in the olfactory bulb, they went on to show that blocking the actions of vasopressin in the bulb in rats blocked their ability to distinguish between familiar and unfamiliar juveniles.

Studying this important hormone and its impact on animal behaviour could support the development of treatments for behavioural disorders in people.

Read more

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.

Why do you get so hungry from smoking weed?

THC (the active ingredient in marijuana) binds to the cannabinoid type-1 (CB1) receptors in the olfactory bulb (sense of smell) of animal brains and stimulates them, which increases the animal’s ability to smell food. Scent and taste are very closely related, with as much as 80% of flavor sensation coming from the smell of food as opposed to the taste.

THC also acts on the nucleus accumbens (part of the pleasure and reward system) of the brain, increasing the release of dopamine (a “pleasure chemical”) that accompanies eating, causing an increase in pleasure that goes along with it.

Finally, another effect of THC’s action on the brain is that it mimics the sensation of being food-deprived, which is believed to be the underlying cause of both the above effects.

So tl;dr - it makes your brain think you’re starving so food smells stronger and tastes better and you feel more pleasure (more rewarded) for eating.