neuronal development

Growing New Neurons

Neurons are specialized cells whose job is to send and receive information in the brain and nervous system. As they grow, neurons extend a single transmission cable — called an axon — from one side of the cell. At the same time, they deploy a set of antennae — called dendrites — on the other side, which allow electrical signals to pass from one neuron to another. 

Using molecular spies that report on biochemical processes inside of living cells, researchers at University of California San Diego School of Medicine were able to observe how the spatial distribution of a key molecule, cyclic AMP, changes during axon growth. Their study is published February 13 by Nature Chemical Biology.

“Our study is the first to show that developmental changes in cyclic AMP gradients determine how rapidly a neuron grows its axon,” said senior author Jin Zhang, PhD, professor of pharmacology at UC San Diego School of Medicine. “By perturbing these gradients, we were even able to make younger neurons grow longer axons and look more like mature neurons, which may help in developing treatments to regenerate injured or damaged nerves.”

Pictured: False-color image of a developing neuron grown in culture for five days, showing a single axon extending downward from the left side of the cell and numerous dendrites protruding from the cell body

This is how super smart octopuses are

The cephalopod’s genome reveals how the creatures evolved intelligence to rival the brightest vertebrates.

We humans think we’re so fancy with our opposable thumbs and capacity for complex thought. But imagine life as an octopus … camera-like eyes, camouflage tricks worthy of Harry Potter, and not two but eight arms – that happen to be decked out with suckers that possess the sense of taste. And not only that, but those arms? They can execute cognitive tasks even when dismembered.

And on top of all that razzmatazz, octocpuses (yes, “octopuses”) have brains clever enough to navigate super complicated mazes and open jars filled with treats.

The octopus is like no other creature on this planet. How did these incredible animals evolve so spectacularly from their mollusk brethren? Scientists have now analyzed the DNA sequence of the California two-spot octopus (Octopus bimaculoides) and found an unusually large genome. It helps explain a lot.

“It’s the first sequenced genome from something like an alien,” says neurobiologist Clifton Ragsdale of the University of Chicago in Illinois, who co-led the genetic analysis, along with researchers from the University of Chicago, the University of California, Berkeley, the University of Heidelberg in Germany and the Okinawa Institute of Science and Technology in Japan.

“It’s important for us to know the genome, because it gives us insights into how the sophisticated cognitive skills of octopuses evolved,” says neurobiologist Benny Hochner who has studied octopus neurophysiology for 20 years.

As it turns out, the octopus genome is almost as large as a human’s and actually contains more protein-coding genes: 33,000, compared with fewer than 25,000 in humans.

Mostly this bonus comes from the expansion of a few specific gene families, Ragsdale says.

One of the most remarkable gene groups is the protocadherins, which regulate the development of neurons and the short-range interactions between them. The octopus has 168 of these genes – more than twice as many as mammals. This resonates with the creature’s unusually large brain and the organ’s even-stranger anatomy. Of the octopus’s half a billion neurons — six times the number in a mouse – two-thirds spill out from its head through its arms, without the involvement of long-range fibers such as those in vertebrate spinal cords.

A gene family that is involved in development, the zinc-finger transcription factors, is also highly expanded in octopuses. At around 1,800 genes, it is the second-largest gene family to be discovered in an animal, after the elephant’s 2,000 olfactory-receptor genes.

Not surprisingly, the sequencing also revealed hundreds of other genes specific to the octopus and highly expressed in particular tissues. For example, the suckers express a unique set of genes that are similar to those that encode receptors for the neurotransmitter acetylcholine. This may be what gives the octopus the spectacular characteristic of being able to taste with its suckers.

The researchers identified six genes for the skin proteins known as reflections. As their names suggests, these alter the way light reflects from the octopus allowing for the appearance of different colors, one of the tricks an octopus uses – along with changing its texture, pattern or brightness – in their mind-blowing ability to camouflage.

When considering the creature’s extraordinary learning and memory capabilities, electrophysiologists had predicted that the genome might contain systems that allow tissues to rapidly modify proteins to change their function; this was also proven to be the case.

The octopus’s position in the Mollusca phylum illustrates evolution at its most spectacular, Hochner says.

“Very simple mollusks like the clam – they just sit in the mud, filtering food,“ he observes. "And then we have the magnificent octopus, which left its shell and developed the most-elaborate behaviors in water.”

Scientists discover new mechanism of how brain networks form

Scientists have discovered that networks of inhibitory brain cells or neurons develop through a mechanism opposite to the one followed by excitatory networks. Excitatory neurons sculpt and refine maps of the external world throughout development and experience, while inhibitory neurons form maps that become broader with maturation. This discovery adds a new piece to the puzzle of how the brain organizes and processes information. Knowing how the normal brain works is an important step toward understanding the nature of neurological conditions and opens the possibility of finding treatments in the future. The results appear in Nature Neuroscience.

“The brain represents the external world as specific maps of activity created by networks of neurons,” said senior author Dr. Benjamin Arenkiel, associate professor of molecular and human genetics and of neuroscience at Baylor College of Medicine, who studies neural maps in the olfactory system of the laboratory mouse. “Most of these maps have been studied in the excitatory circuits of the brain because excitatory neurons in the cortex outnumber inhibitory neurons.”

The studies of excitatory maps have revealed that they begin as a diffuse and overlapping network of cells. “With time,” said Arenkiel, “experience sculpts this diffuse pattern of activity into better defined areas, such that individual mouse whiskers, for instance, are represented by discrete segments of the brain cortex. This progression from a diffuse to a refined pattern occurs in many areas of the brain.”

In addition to excitatory networks, the brain has inhibitory networks that also respond to external stimuli and regulate the activity of neural networks. How the inhibitory networks develop, however, has remained a mystery.

In this study, Arenkiel and colleagues studied the development of maps of inhibitory neurons in the olfactory system of the mouse.

Studying inhibitory brain networks of the mouse sense of smell

“Unlike sight, hearing or other senses, the sense of smell in the mouse detects discrete scents from a large array of molecules,” said Arenkiel, who is also a McNair Scholar at Baylor.

Mice can detect a vast number of scents thanks in part to a complex network of inhibitory neurons. Inhibitory neurons are the most abundant type of cells in the mouse brain area dedicated to process scent. To support this network, newly born inhibitory neurons are continually added and integrated into the circuits.

Arenkiel and colleagues followed the paths of these newly added neurons in time to determine how inhibitory circuits develop. First, they genetically labeled the cells so they would glow when the neurons were active. Then, they offered individual scents to the mice and visually recorded through a microscope the areas or networks of the brain that glowed for each scent the live, anesthetized animal smelled. The scientists repeated the experiment several times to determine how the networks changed as the animal learned to identify each scent.

Surprising result

The scientists expected that inhibitory networks would mature in a way similar to that of excitatory networks. That is, the more the animal experienced a scent, the better defined the networks of activity would become. Surprisingly, the scientists discovered that the inhibitory brain circuits of the mouse sense of smell develop in a manner opposite to the excitatory circuits. Instead of becoming narrowly defined areas, the inhibitory circuits become broader. Thanks to this new finding scientists now better understand how the brain organizes and processes information.

Arenkiel and colleagues think that the inhibitory networks work hand-in-hand with the excitatory networks. They propose that the interaction between excitatory and inhibitory networks could be compared to a network of roads (excitatory networks) whose traffic is regulated by a network of traffic lights (inhibitory networks). The scientists suggest that the formation of useful neural maps depends on inhibitory networks driving the refinement of excitatory networks, and that this new information will be essential towards developing new approaches for repairing brain tissue.

This image shows a group of neurons in a mouse’s brain. The whole group measures about the width of a human hair and is part of the brain’s somatosensory area, which maps senses to the part of the body where they were experienced. This is the part of the sensory system that tells you a pain is coming from your foot or that a friend’s tap is on your shoulder.

The 3-D image of a tiny proportion of the mouse brain’s 75 million neurons is a composite developed by cutting several hundred 30-nanometer-thick slices of mouse brain tissue. Each slice was then imaged in sequence using an electron microscope, according to the Howard Hughes Medical Institute. The stack of images was reconstructed in 3-D and colored to better visualize individual neurons and the connections between them.

Image courtesy: Daniel Berger, MIT. EM data from N. Kasthuri, R. Schalek, K. Hayworth, J.C. Tapia, and J. Lichtman/Harvard. Reconstruction and rendering by D. Berger and S. Seung at MIT.

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Scientists Develop Antibody to Treat Traumatic Brain Injury and Prevent Long-Term Neurodegeneration

New research led by investigators at Beth Israel Deaconess Medical Center (BIDMC) provides the first direct evidence linking traumatic brain injury to Alzheimer’s disease and chronic traumatic encephalopathy (CTE) – and offers the potential for early intervention to prevent the development of these debilitating neurodegenerative diseases. TBI can result from repetitive contact sport injuries or from exposure to military blasts, and is one of the most significant risk factors for both Alzheimer’s disease and CTE.

In a study published in the online edition of the journal Nature, the researchers found that a misshapen isoform of the tau protein can develop as soon as 12 hours after TBI, setting in motion a destructive course of events that can lead to widespread neurodegeneration. Importantly, the researchers have developed a potent antibody that can selectively detect and destroy this highly toxic protein.

“TBI is a leading cause of death and disability in children and young adults and also affects approximately 20 percent of the more than two million troops who have deployed to Iraq and Afghanistan,” said co-senior author Kun Ping Lu, MD, PhD, Chief of the Division of Translational Therapeutics in the Department of Medicine at BIDMC and Professor of Medicine at Harvard Medical School (HMS). “Our study shows that an early neurodegenerative process induced by the toxic tau protein can begin just hours after a traumatic brain injury. In both cell models of stress and in mouse models simulating sport- and military-related TBI, the production of this pathogenic protein, called cis P-tau, disrupts normal neurological functioning, spreads to other neurons and leads to widespread neuronal death. We have developed a potent monoclonal antibody that can prevent the onset of widespread neurodegeneration by identifying and neutralizing this toxic protein and restoring neurons’ structural and functional abilities.”

Alzheimer’s disease is the most common form of dementia in older individuals and currently affects more than 5 million Americans and 30 million people worldwide. Chronic traumatic encephalopathy is a degenerative brain disease associated with a number of neurological symptoms including risk-taking, aggression and depression. CTE can also lead to progressive dementia.

Previous research has shown that abnormal phosphorylation of the tau protein underlies Alzheimer’s and other neurodegenerative diseases. In recent years, the Lu laboratory discovered that tau exists in two isoforms, or shapes – one functioning and one disease-causing.

“Healthy tau protein is found in the brain and serves to assemble and support microtubules, the ‘scaffolding systems’ that give neurons their unique shape and are integral to memory and normal brain functioning,” explained Lu. But in Alzheimer’s, CTE and other neurodegenerative diseases, collectively called tauopathies, tau becomes tangled and unable to function properly.

“Recent studies of CTE in the brains of boxers, American football players and blast-exposed veterans have identified extensive neurofibrillary tau tangles,” he said. “But, because these tangles were not detected until months or, more likely, years after TBI, it has not been known whether tauopathy is a cause or a consequence of TBI-related neurodegenerative disease. We have now shown that it is a cause of these diseases.”

Co-senior author of the new study Xiao Zhen Zhou, MD, also an investigator in BIDMC’s Division of Translational Therapeutics and Assistant Professor of Medicine at HMS, had previously developed polyclonal antibodies capable of distinguishing between two distinct isoforms of the phosphorylated tau protein. The isoform known as trans is in a relaxed shape and is important for normal brain functioning. The other isoform, known as cis, is in a twisted shape and is prone to becoming tangled. Cis P-tau is an early pathogenic protein leading to tauopathy and memory loss in Alzheimer’s disease.

“In this new study, we wanted to find out whether cis P-tau is present following TBI and, if so, how to eliminate it from the brain without disrupting the healthy functioning of trans P-tau,” said Zhou. “We generated a monoclonal antibody able to detect and eliminate cis P-tau very early in the disease process.”

Monoclonal antibody technology is a popular drug development approach. Working like a lock and key, it enabled the investigators to both detect and neutralize only the toxic cis P-tau.

After confirming the existence of this toxic cis tau isoform in the brain tissue of humans who had died of CTE, the authors simulated contact-sport and blast-related injuries in mouse models, and found that the brain’s induction of cis P-tau is dependent on injury severity and frequency.

“Mild TBI, also known as a concussion, results in moderate and transient cis P-tau induction,” explained Lu. “However, repetitive concussions, as might occur in contact sports, can result in robust and persistent cis P-tau induction. This is similar to what is produced following a single severe TBI caused by a blast or impact.”
Subsequent experiments revealed that the cis P-tau protein disrupts the brain’s microtubule scaffolding systems and the transport of mitochondria, the powerhouse that provides energy for neuronal function, and eventually leads to neuron death by apoptosis. The research also showed that, over time, cis P-tau progressively spreads throughout the brain. Treating TBI with cis antibody eliminated the toxic cis P-tau, prevented widespread tauopathy and neuron death and restored brain structure and function.

“These experiments told us that cis P-tau has the ability to kill one neuron after another, eventually leading to widespread neurofibrillary tangles and brain atrophy, which are the hallmark lesions of both Alzheimer’s disease and CTE,” said Lu. “We have determined that cis P-tau is an early driver of neurodegenerative disease after brain injury and that tauopathy it is a cause of TBI-related Alzheimer’s disease and CTE. We have also determined that the cis antibody can treat TBI and prevent its long-term consequences in mouse models. The next important steps will be to establish cis P-tau as a new biomarker to help enable early detection, and to humanize the cis antibody for treating patients with TBI.”

“Alzheimer’s disease and chronic traumatic encephalopathy are terrible diseases that progressively rob individuals of their memory, judgment and ability to function,” said study coauthor Alvaro Pascual-Leone, MD, PhD, Chief of the Division of Cognitive Neurology at BIDMC and Professor of Neurology at HMS. Pascual-Leone also serves as Associate Director of the Football Players Health Study (FPHS) at Harvard University, a multi-year initiative to discover new approaches to diagnose, treat and prevent injuries in professional football players.

“High-profile cases of CTE, such as that of the late football player Junior Seau, have vividly demonstrated the tragic consequences of this affliction,” he added. “We need to learn more about CTE’s causes in order to develop better ways of diagnosing and treating it, and this study offers us a promising early intervention to prevent the pathologic consequences of this disease. These findings additionally offer us a new way to approach Alzheimer’s disease, which poses a staggering unsustainable burden throughout the world. Alzheimer’s afflicts both individuals and their families and, it deprives society of the contributions of experienced and wise elders.”

Brain Boost: Research to Improve Memory through Electricity

In a breakthrough study that could improve how people learn and retain information, researchers at the Catholic University Medical School in Rome significantly boosted the memory and mental performance of laboratory mice through electrical stimulation.

The study, sponsored by the Office of Naval Research (ONR) Global, involved the use of Transcranial Direct Current Stimulation, or tDCS, on the mice. A noninvasive technique for brain stimulation, tDCS is applied using two small electrodes placed on the scalp, delivering short bursts of extremely low-intensity electrical currents.

“In addition to potentially enhancing task performance for Sailors and Marines,” said ONR Global Commanding Officer Capt. Clark Troyer, “understanding how this technique works biochemically may lead to advances in the treatment of conditions like post-traumatic stress disorder, depression and anxiety—which affect learning and memory in otherwise healthy individuals.”

The implications of this research also have great potential to strengthen learning and memory in both healthy people and those with cognitive deficits such as Alzheimer’s.

“We already have promising results in animal models of Alzheimer’s disease,” said Dr. Claudio Grassi, who leads the research team. “In the near future, we will continue this research and extend analyses of tDCS to other brain areas and functions.”

After exposing the mice to single 20-minute tDCS sessions, the researchers saw signs of improved memory and brain plasticity (the ability to form new connections between neurons when learning new information), which lasted at least a week. This intellectual boost was demonstrated by the enhanced performance of the mice during tests requiring them to navigate a water maze and distinguish between known and unknown objects.

Using data gathered from the sessions, Grassi’s team discovered increased synaptic plasticity in the hippocampus, a region of the brain critical to memory processing and storage.

Although tDCS has been used for years to treat patients suffering from conditions such as stroke, depression and bipolar disorder, there are few studies supporting a direct link between tDCS and improved plasticity—making Grassi’s work unique.

More important, the researchers identified the actual molecular trigger behind the bolstered memory and plasticity—increased production of BDNF, a protein essential to brain growth. BDNF, which stands for “brain-derived neurotrophic factor,” is synthesized naturally by neurons and is crucial to neuronal development and specialization.

“While the technique and behavioral effects of tDCS are not new,” said ONR Global Associate Director Dr. Monique Beaudoin, “Dr. Grassi’s work is the first to describe BDNF as a mechanism for the behavioral changes that occur after tDCS treatment. This is an exciting and growing research area of great interest to ONR.”

Beaudoin said tDCS treatment could one day benefit Sailors and Marines, from helping them learn faster and more effectively to easing the effects of post-traumatic stress disorder.

“Our warfighters face tremendous challenges that are both physically and cognitively taxing,” she said. “They perform their duties in stressful environments where there are often suddenly and randomly varying levels of environmental stimulation, disrupted sleep cycles and a constant need to stay alert and vigilant.

“We want to explore all interventions that could help them stay healthy and perform optimally in these environments—especially when treatments are potentially noninvasive, effective and lead to long-lasting changes.”

Learn more about the work of Grassi and his team, which was published in Scientific Reports.

Imagine after civil war when the dust has settled and friendships have been mended tony decides as a way to make things up to bucky to develop synthetic neurons for bucky’s robotic arm so that he can actually feel and touch. Now imagine bucky walking around the lab right after the procedure and just lifting things and feeling the texture of certain equipment a bright smile on his face the whole time when steve walks in and with tears now in his eyes bucky gently places his metal hand over steve’s chest and lets the tears fall freely as he feels the warmth of his skin and the steady heart beat.

chromacolors  asked:

Does the Spider gene have any equivalents in other species?

Yes, actually. Dark colors in animals come from melanin which is produced by special cells called melanocytes. When an animal is developing the malanocytes and the neurons of the neural crest (which will eventually become the spinal chord) aren’t differentiated from one another. At some point in development they do differentiate and the malanocytes migrate away from the neural crest to the regions in the body where melanin will need to be produced (the areas with dark coloring). The spider gene produces that particular dark pattern by disrupting the migration of the melanocytes as they leave the neural crest, but in the process it also messes up the development of the neurons in the neural crest (since those two types of cells are so closely associated) which causes neurological problems.

A lot of animals with spotty patterns have a gene that causes a similar disruption of melanocyte migration, and while some of these cause neurological issues they don’t usually cause the same wobble as the spider gene. For example a lot of blue-eyed Dalmatians experience congenital deafness because the genes that stop melanocytes from migrating to their eyes also mess up the neuronal development of the inner ear.

Interestingly melanin has protective properties for the brain and neurons. Animals that lack melanin (often with coat color lacking dark pigments or with blue eyes) are at greater risk of blindness, deafness, or just being more high strung and anxious. Whereas animals with more melanin tend to be calmer and less sensitive to stress. 

Note that there is no science I am aware of that suggests this applies to humans of different skin/hair/eye colors. Even pale people still have the necessary levels of melanin; these neurological and behavioral issues usually only arise when melanin has been artificially selected against in human-bred animals. Just want to be abundantly clear on that.

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These Brain Cells Have Bite

by Michael Keller

One could be forgiven for assuming the cells pictured above are neurons, the fundamental units that comprise the brain and nervous system. With branching dendrites growing off central nucleus-containing somas and thin axons reaching out to communicate with other cells, they basically are neurons. 

The thing is that these cells didn’t come from the brain, spinal cord or nerves–they came from teeth. Researchers at Australia’s University of Adelaide have pushed stem cells from the teeth of adult mice to morph into ones very much like neurons. 

They say that though the new cells aren’t quite neurons yet, they can link up into networks with potentially huge benefits for stroke sufferers. They also expect for the cells to become much more like neurons as they refine their technique.

“The reality is, treatment options available to the thousands of stroke patients every year are limited,” said Kylie Ellis, who conducted the research as a doctoral student. "Stem cells from teeth have great potential to grow into new brain or nerve cells, and this could potentially assist with treatments of brain disorders, such as stroke.“

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Fruit-fly brains filmed in action

This is the crackle of neural activity that allows a fruit-fly (Drosophila melanogaster) larva to crawl backwards: a flash in the brain and a surge that undulates through the nervous system from the top of the larva’s tiny body to the bottom. When the larva moves forwards, the surge flows the other way.

The video — captured almost at the resolution of single neurons — demonstrates the latest development in  a technique to film neural activity throughout an entire organism. The original method was invented by Philipp Keller and Misha Ahrens at the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia. The researchers genetically modify neurons so that each cell fluoresces when it fires; they then use innovative microscopy that involves firing sheets of light into the brain to record that activity.

In 2013, the researchers produced a video of neural activity across the brain of a (transparent) zebrafish larva1. The fruit-fly larva that is mapped in the latest film, published in Nature Communications on 11 August2, is more complicated. The video shows neural activity not just in the brain, but throughout the entire central nervous system (CNS), including the fruit-fly equivalent of a mammalian spinal cord. And unlike the zebrafish, the fruit fly’s nervous system is not completely transparent, which makes it harder to image.

Nature doi:10.1038/nature.2015.18164