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Rats Engineered to See Infrared Light, Use It to Seek Out Water [1562]

de System Administrator - miércoles, 11 de noviembre de 2015, 20:23
 

Rats Engineered to See Infrared Light, Use It to Seek Out Water

BY SHELLY FAN 

The brain is a great information processor, but one that doesn’t care about where information comes from.

Sight, scent, taste, sound, touch — all of our precious senses, once communicated to the brain, are transformed into simple electrical pulses. Although we consciously perceive the world through light rays and sound waves, the computing that supports those experiences is all one tone — electrical.

 

Simply put, all of our senses are the same to our brain.

It’s a strange notion that’s led to some even stranger “sensory substitution” experiments.

In 1969, the late neuroplasticity pioneer Dr. Paul Bach-y-Rita designed a vision replacement setup that looked straight out of the mind of 1950s-era sci-fi master Isaac Asimov.

Picture this: rows and rows of tiny vibrating needles, 400 in total, were mounted on the back of a menacing-looking dental chair. Blind subjects sat in the chair, exposing the sensitive skin on their backs to the vibration matrix.

Mounted close to the arm of the chair was an old-school video camera, which captured black-and-white images of objects placed in front of the chair. The image from the camera was converted into a 400-pixel “image” (a kind of pressure map) using the vibrating needles. Each camera pixel corresponded to a needle in the vibration matrix — black “pixels” produced a strong jab from a corresponding needle, whereas white pixels produced only a gentle touch.

It was a big, clunky and slow setup — but it worked.

After training, blind subjects not only learned to discriminate between squiggles, shapes and faces, but could also analyze complex visual scenes — involving more than three people or partially concealed objects — with just their skin.

But here’s the real kicker: the vibrations weren’t computed in the patients’ sensory cortex; instead, theywere processed in their visual cortex.

Somehow, the patients’ defunct visual processing centers adopted the tactile information as their own. The end result? The patients “saw” with their skin.

Since then, sensory substitution has allowed the blind to see with musicread with sound, and has given balance back to motor impaired patients by providing relevant information to their tongues.

Yet all these experiments were done in patients with one or more defective senses. This led Duke neuroengineers Dr. Eric Thomson and Dr. Miguel Nicolelis to ask: what if we did this to a healthy brain? Could we “program in” additional senses?

What the heck, thought Thomson, let’s give rats infrared vision.

Let there be (infrared) light

Thomson began his experiment by designing a small bi-module implant only a few millimeters wide. The implant sent the output of a head-mounted infrared detector to a microarray of electrical microstimulators, which were fitted onto a rat’s sensory cortex (specifically, the parts that respond to touch signals coming in from their whiskers).

He then trained water-deprived rats to discriminate between three ports in a circle-shaped arena. Each of the ports emitted visible light in a random order; all the rats had to do was walk over to the lit port to get their water reward.

Once the rats learned the rules of the game, Thomson switched over to infrared.

 

Rat and headmounted infrared detector. Image Credit: Eric Thomson/Duke University.

Different intensities of infrared light, captured by the detectors mounted on top of the rats’ heads, were given a value and transformed into different electrical simulation patterns. The patterns were then sent to the microstimulator, which communicated the desired current pulses to the sensory cortex in real time.

We wanted the animals to process graded infrared intensities, not just binary on-or-off, said Thomson. After all, we don’t experience visible light as all-or-none.

At first, the rats seemed confused — in response to stimulation, instead of going to the infrared source, they sat and groomed their whiskers as if being touched by an external force (which in a sense they were, since their sensory cortex was being zapped).

After roughly a month of training, however, all six animals adapted to their infrared headgear, learning to forage with infrared.

We could see that they were sweeping their heads side-to-side to better detect where the infrared light waves were coming from, said Thomson. This led to them correctly picking out the water-containing port over 70% of the time.

Additional tests confirmed the rats could still detect whisker “touch information” just fine — the new infrared “sense” didn’t boot out an existing capability.

“We have implemented, as far as we can tell, the first cortical neuroprosthesis capable of expanding a species’ perceptual repertoire to include the near infrared electromagnetic spectrum,” wrote Thomson in a2013 report of the study published in Nature Communications.

Lightning-fast sensory integration

As cool as that study was, Thomson wasn’t satisfied.

For one, the rats only had one infrared detector, which severely limited depth perception. For another, the rats were technically “feeling” not “seeing” infrared, since their sensory cortices were doing all the hard work.

In a new series of experiments, reported recently at the 2015 Society for Neuroscience annual conference in Chicago, Thomson inserted three additional electrodes into the rats’ brains to give them 360 degrees of panoramic infrared perception.

The tweak boosted how fast the animals adopted infrared by almost 10 fold. When primed to perform the same water-seeking task, they learned in just 4 days, compared to 40 days with only a single implant.

“Frankly, this was a surprise,” said Thomson to Science News. “I thought it would be really confusing for [the rats] to have so much stimulation all over their brain, rather than [at] one location.”

But the biggest “whoa” moment came when he re-implanted electrodes into the rats’ visual cortex: this time, it took only a single day for the animals to learn the water task.

Why would redirecting infrared traffic to the visual brain regions speed up learning? Thomson isn’t quite sure, but he thinks it has to do with the nature of infrared light.

After all, our visual cortex is optimized to process visible light, which is very close to infrared in terms of wavelength. Maybe the visual cortex is “primed” to process infrared in a way that the sensory cortex isn’t.

Without digging deeper and looking at changes in plasticity at different levels of the visual system, however, we can’t tell for sure, says Thomson. What we do know, however, is that the visual cortex can do both jobs — visible light and infrared — simultaneously.

Augmenting senses is limited to animals for now, although biohackers are busy at work extending the human visible light spectrum into the near infrared.

Thomson’s study suggests that it’s possible — if we get “infrared eye” hardware working, our brains will likely rapidly adapt.

Frankly, I’m still amazed, Thomson said. The brain is always hungry for new sources of information, but it’s incredibly auspicious for the field of neuroprosthetics and augmentation that it can absorb this completely foreign type so quickly.

Our work suggests that sensory cortical prostheses, in addition to restoring normal neurological functions, may serve to expand natural perceptual capabilities in mammals, he said.

“And that’s why I’m excited.”

Image Credit: Shutterstock.com; Eric Thomson/Duke University

Related Topics:

Link: http://singularityhub.com

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Ray Kurzweil’s Wildest Prediction: Nanobots Will Plug Our Brains Into the Web by the 2030s [1507]

de System Administrator - lunes, 12 de octubre de 2015, 20:03
 

 

Ray Kurzweil’s Wildest Prediction: Nanobots Will Plug Our Brains Into the Web by the 2030s

By Peter Diamandis

I consider Ray Kurzweil a very close friend and a very smart person. Ray is a brilliant technologist, futurist, and a director of engineering at Google focused on AI and language processing. He has also made more correct (and documented) technology predictions about the future than anyone:

As reported, "of the 147 predictions that Kurzweil has made since the 1990s, fully 115 of them have turned out to be correct, and another 12 have turned out to be "essentially correct" (off by a year or two), giving his predictions a stunning 86% accuracy rate."

Two weeks ago, Ray and I held an hour-long webinar with my Abundance 360 CEOs about predicting the future. During our session, there was one of Ray's specific predictions that really blew my mind.

"In the 2030s," said Ray, "we are going to send nano-robots into the brain (via capillaries) that will provide full immersion virtual reality from within the nervous system and will connect our neocortex to the cloud. Just like how we can wirelessly expand the power of our smartphones 10,000-fold in the cloud today, we'll be able to expand our neocortex in the cloud."

Let's digest that for a moment.

2030 is only 15 years away…

Directly plugging your brain into the internet? Upgrading your intelligence and memory capacity by orders of magnitude?

This is a post about the staggering (and fun) implications of that future.

The Basics

The implications of a connected neocortex are quite literally unfathomable. As such, any list I can come up with will pale in comparison to reality…but here are a few thoughts to get the ball rolling.

Brain-to-Brain Communication

This will deliver a new level of human intimacy, where you can truly know what your lover, friend or child is feeling. Intimacy far beyond what we experience today by mere human conversation. Forget email, texting, phone calls, and so on — you'll be able to send your thoughts to someone simply by thinking them.

Google on the Brain

You'll have the ability to "know" anything you desire, at the moment you want to know it. You'll have access to the world's information at the tip of your neurons. You'll be able to calculate complex math equations in seconds. You'll be able to navigate the streets of any cities, intuitively. You'll be able to hop into a fighter jet and fly it perfectly. You'll be able to speak and translate any language effortlessly.

Scalable Intelligence

Just imagine that you're in a bind and you need to solve a problem (quickly). In this future world, you'll be able to scale up the computational power of your brain on demand, 10x or 1,000x…in much the same way that algorithms today can spool up 1,000 processor cores on Amazon Web Service servers.

Living in the Virtual World

If our brains can truly connect at high bandwidth, you will be able to bypass our current sensory organs (eyes, ears, touch) to the point where brain's perception of reality can be driven completely by a gaming engine — a virtual world. Likewise, the connections would exist in the motor cortex of your brain as well. When you move your limbs, imagine a corresponding set of virtual limbs (your avatar) moving perfectly in the virtual world. This is about creation of The Matrix x 1,000.

Extended Immune System

In my webinar discussion with Ray, he outlined how we already have intelligent biological devices, the size of blood cells, that kill disease. They are called T-cells. They can recognize an enemy and attack it, but they don't work on cancer, retroviruses, et cetera. In the future, nanorobots will be able to communicate wirelessly, download software when new pathogens arrives, and attack cancer, cancer stem cells, bacteria, viruses, and all the disease agents. They can also work on metabolic diseases like diabetes. They could also maintain healthy levels of everything you need in the blood, including nutrients, and basically repair and eventually replace damaged organs.

Downloadable Expertise

Remember the scene in The Matrix where Trinity needs to learn how to fly a helicopter, and Tank downloads a program teaching her how to do it? We'll be able to do this. Need to perform emergency surgery? Just download the ER doctor program. Need to learn a new language? Download it. Want to cook the perfect meal? Download the chef module. In fact, you probably won't even need to download it — which takes up memory — you'll probably just "stream" expertise from the cloud.

Expanded and Searchable Memories

We'll be able to remember everything that ever happened to us (because we'll store our memories in the cloud), and we'll be able to search that memory database for useful information. When our memories will become searchable, we'll also be able to make them contextual by cross-referencing our calendars, GPS coordinates, health data, stock market, current news, weather conditions, and anything else that might be relevant to that particular moment in time.

A Higher-Order Existence

Ray talks about how a connected neocortex will bring humanity to a higher order of existence and complexity — expanding our palate for emotion, art, humor, creativity, expression, and uniqueness. He says, "We're going to be funnier. We're going to be sexier. We're going to be better at expressing loving sentiment. We're going to add more levels to the hierarchy of brain modules and create deeper levels of expression. People will be able to very deeply explore some particular type of music in far greater degree than we can today. It'll lead to far greater individuality, not less."

While this future may sound fanciful to many, let's remember that exponential technologies are initially deceptive, before they become disruptive. And today, there are many labs around the world working on molecular machinery, CRISPR/Cas9 systems that allow us to edit our own genome, and brain-computer interfaces (through cortical implants and the field of optogenetics).

So what if these fields of technological progress double every 18 months? In 15 years (2015 - 2030), we will have a 1,000-fold improvement over today. What does a future one thousand times better look like? Perhaps it's what Ray describes…

If this future becomes reality, connected humans are going to change everything. We need to discuss the implications in order to make the right decisions now so that we are prepared for the future.

Image Credit: Shutterstock.com

 

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Reality as a Service [1754]

de System Administrator - jueves, 13 de abril de 2017, 12:33
 

Jordan Springs in Western Sydney: 2009 vs 2017 | Image: Supplied

Nearmap eyes 'reality-as-a-service' with 3D mapping technology

By Asha McLean

The Australian-listed aerial imagery company will be giving businesses access to 3D models of what's on the ground with a new 3D mapping technology scheduled for launch later this year.

Australian aerial imagery company Nearmap has revealed that it will be launching new technology later this year, expected to give businesses access to 3D models of what's on the ground.

Having already transformed an industry that was almost non-existent, Nearmap CEO Rob Newman told ZDNet that moving into 3D is simply the next phase of reshaping the industry.

The Australian Securities Exchange-listed company has already extended its camera system to process 3D data, as an extension of the 2D collection Nearmap has been performing for years.

"We are starting to collect that content in both Australia and the US, and that will be available as a streamed subscription service to our customers," Newman explained.

"We're capturing the real world, and then allowing our customers to stream it to be presented in a variety of different forms such as textured mesh or 3D visualisations."

Internally, Newman said the imminent offering is being called "reality as a service".

The CEO said Nearmap has committed to capture all capital cities in Australia as well as the top 50 percent of the US population centres by the end of this calendar year in 3D, noting that collection is already under way.

"Instead of going out in your car and checking overhanging tree branches or slopes of a roof, for example, all of that kind of information will be available in the third dimension," he said.

Newman found himself involved in Nearmap back in 2008, when founder Stuart Nixon approached the then-venture capitalist for investment. Nearmap was instead acquired by ASX-listed Ipernica that same year, and ran as a wholly owned subsidiary of Ipernica until 2012, when Nearmap was moved to Sydney from Perth and made the primary entity of the company after the success of its first product release in 2009.

"I remember speaking with Stuart, sitting in his lounge room and him showing me a demonstration of the technology and I thought this is going to change the world, and I've been passionate about it ever since," said Nixon, who took up the role of CEO in 2015 after spending seven years on Nearmap's board.

The company's product development, technology development, and centralised functions all operate out of the Sydney headquarters. Nearmap also has a sales presence across the United States, where Newman said the company's product has gained a warm reception.

According to Newman, Nearmap created a new market when it introduced its product, as 80 percent of its customers in Australia had never before purchased aerial imagery.

In Australia, Nearmap captures imagery up to six times per year for most of the major cities and some of the larger regional towns. In the US, 70 of the country's largest cities are captured up to three times per year, with 270 cities captured at least once a year.

Insurance companies are using Nearmap to remotely assess claims; construction companies are using it to monitor the progress of developments; solar companies are using it to provide quotes and identify areas to target for new business; and local government agencies are using it to identify illegal developments.

While it's obvious what customers such as Ausgrid and Brisbane City Council are using Nearmap for, Newman said he's seen a whole range of use cases he never saw coming.

"One is Tasty Trucks, who drive the food vans around to construction sites so that the workers on site can buy lunch," he explained. "Tasty trucks was identifying where construction sites were using our imagery to plan the route of their food trucks."

Nearmap also has a partnership with Dutch telematics company TomTom.

"When you use your smartphone to plan your trip and it gives you the routing directions, they're also tracking where you're going, and when they find out that the route you took was different than what they have as a record, they look at Nearmap imagery," he explained. "They might find changes such as new roundabouts and change their routing directions as a result."

Newman believes there is real opportunity with Nearmap around driverless cars and autonomous vehicles in the future.

"When you think about what has happened with other subscription-type businesses like music and software, we're doing the same in this industry and I think there's enormous potential for this company," he said.

"Going into the third dimension and delivering reality as a service, we can't even think today about all of the applications that could bring, in the same way we would never have guessed the Tasty Trucks example.

"Once you've got that visualisation of whatever is on the ground, a developer, for example, could show what the view from the 23rd floor of a building would look like."

Link: http://www.zdnet.com

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Relación entre la flora intestinal y la salud mental [1047]

de System Administrator - miércoles, 7 de enero de 2015, 15:49
 

 

La relación entre la flora intestinal y la salud mental

Hace muchos años que los científicos tienen conocimiento de la conexión entre el cerebro y el intestino. Es ampliamente conocido que una depresión nos puede distorsionar el apetito o también estar vinculada a problemas como diarrea o estreñimiento. Sin embargo, hasta hace no muchos años los investigadores creían que la comunicación entre estos dos órganos era de una sola manera: desde el cerebro hasta el intestino. Pero algunas investigaciones realizadas sobre la flora microbiana intestinal humana han revelado que este proceso de comunicación es similar a muchos otros procesos neurológicos, de ida y vuelta, es decir, del cerebro al intestino y del intestino al cerebro.

También se sabe que haciendo cambios en la flora microbiana intestinal (conjunto de bacterias que viven en nuestro intestino) es posible modificar el comportamiento humano. Esto está cambiando la forma de entender tanto los trastornos mentales como los desórdenes de alimentación.

Es sabido que cierta exposición de recién nacidos y niños pequeños es fundamental para el desarrollo de una flora intestinal robusta y que esto tiene un impacto determinante sobre el desarrollo y la función del tracto gastrointestinal, sistema inmunológico, neuroendocrino y los sistemas metabólicos.

Además, investigaciones en animales demuestran que la administración de antimicrobianos orales en ratones libres de patógenos provoca una modificación transitoria de la composición de la flora intestinal y que paralelamente se alteran algunas proteínas en el hipocampo implicadas en el desarrollo de estados de ansiedad y estrés. También se observó que después de esto, en algunos ratones adultos no había una rápida vuelta a la normalidad en la flora bacteriana y que durante este tiempo se producía una adaptación a los niveles de estrés y ansiedad.
Si tenemos en cuenta la cantidad de antibióticos que rutinariamente consumen las personas, deberíamos preocuparnos en la incidencia que estos productos pudieran tener en las distintas enfermedades mentales entre la población.

Afortunadamente también hay evidencia de que si ajustamos el nivel de estas bacterias podemos producir importantes cambios conductuales y psicológicos. En un reciente estudio, ratones con estrés inducido fueron dosificados con el probiótoco Lactobacilo rhamnosus, estos mostraron niveles más bajos de ansiedad, disminución de las hormonas del estrés e incluso cambios en los receptores del cerebro de neurotransmisores vitales para la reducción de los estados de ansiedad.

Es indudable que el uso de probióticos para el tratamiento del comportamiento humano es cada vez más evidente. En 2013 científicos de la UCLA realizaron un estudio con un grupo de mujeres que consumieron una bebida con cuatro cepas probióticas durante cuatro semanas, pasado ese tiempo las participantes mostraron una actividad sustancialmente menor en las redes neuronales que se alteran en una situación de estrés.

Hasta que se publicó el estudio de la UCLA la idea de que las bacterias probióticas administradas al intestino podrían influir en el comportamiento de las personas parecía algo poco realista. Sin duda que la capacidad de los probióticos de afectar los procesos cerebrales humanos es uno de los más emocionantes acontecimientos recientes de la investigación científica.

Link: http://web-salud.blogspot.com

 
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Remediation of addiction with a 1-2 punch of deep brain stimulation & dopamine receptor antagonists [1154]

de System Administrator - jueves, 12 de marzo de 2015, 15:06
 

Remediation of addiction with a 1-2 punch of deep brain stimulation & dopamine receptor antagonists

by Greg Bissonette PhD

Pathological changes to synaptic transmission underlie part of the etiology of different neurological and psychiatric diseases including Parkinson’s disease and drug addiction. Deep brain stimulation (DBS) is an effective treatment for tremors associated with Parkinson’s disease.1 Recent optogenetic experiments have shown that both synaptic transmission and addiction-related behaviors are normalized by stimulation of medium spiny neurons (MSNs) through depotentiation of D1 receptor (D1R) expressing neurons in the nucleus accumbens (NAc).

These optogenetic experiments suggest an enticing therapeutic potential. However, optogenetic protocols are not approved for human use. On the other hand, DBS is a U.S. Food and Drug Administration (FDA)-approved treatment for Parkinson’s disease and evidence supports a possible use for DBS in treating addiction.2 However, the therapeutic benefits of DBS are highly transient and therapeutic duration needs to be increased. In a recent article published in Science, Creed, Pascoli and Lüscher demonstrate that a combination of DBS and pharmaceuticals leads to long-term improvement in synaptic transmission and addiction-related behavior. 

The researchers used cocaine locomotor sensitization (a long-term enhancement of locomotor activity after repeated cocaine experience) and AMPA/NMDA receptor ratio (a measure of synaptic potentiation) to investigate addiction-related physiology. Five days of cocaine administration induced locomotor sensitization and increased AMPA/NMDA ratio in mice. Using a combination of optogenetics and pharmacology, Creed et al., were able to show in brain slices that a low stimulation frequency induced long-term depression of excitatory synapses onto D1R-expressing MSNs when used in conjunction with D1R antagonists, SCH23390 or SCH39166. When repeating this in vivo, they were able to show that the combination of low frequency optogenetic stimulation in the NAc shell and infusion of D1-antagonists abolished cocaine locomotor sensitization.

Finally, the researchers demonstrated that either 12-hz DBS or D1-antagonists alone had no impact on locomotor sensitization, but when both treatments were used together, they were able to significantly reduce locomotor sensitization in the animals without impairing the immediate response to cocaine. Importantly, cocaine sensitization in DBS and D1-anatagonist treated mice was still suppressed even if treatment occurred a week before a cocaine challenge, supporting the long-lasting impact of this treatment.

As DBS and D1-antagonist (SCH39166) are FDA-approved for human use, this study supports a potentially powerful role for already available therapies in the treatment of addiction.  These experiments demonstrate a role for DBS in reversing the potentiation of excitatory neurotransmission onto D1R-expressing MSNs in the NAc shell, and suggest a methodology for translating optogenetically realized findings into potential DBS treatment protocols.

Publication

Creed M, Pascoli VJ, Lüscher C (2015) Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology. Science 347(6222):659-664. doi: 10.1126/science.1260776

References
  1. Miocinovic S, Somayajula S, Chitnis S, Vitek JL (2013) History, applications, and mechanisms of deep brain stimulation. JAMA Neurology 70(2):163-171. doi: 10.1001/2013.jamaneurol.45
  2. Williams NR, Okun MS (2013) Deep brain stimulation (DBS) at the interface of neurology and psychiatry. The Journal of Clinical Investigation 123(11):4546–4556. doi: 10.1172/JCI68341

Tags

Link: http://www.neuroscientistnews.com

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Repairing neurons with light [1587]

de System Administrator - martes, 17 de noviembre de 2015, 18:12
 

Zebrafish neurons projecting to the brain (green). One neuron expresses a light-activatable enzyme (red). Scientist were able to stimulate the regeneration of injured neurons using optogenetics. Credit: Helmholtz Zentrum München

Bright prospects: Repairing neurons with light

by Editor

The nervous system is built to last a lifetime, but diverse diseases or environmental insults can overpower the capacity of neurons to maintain function or to repair after trauma. A team led by Dr. Hernán López-Schier, head of the Research Unit Sensory Biology and Organogenesis at Helmholtz Zentrum München, now succeeded in promoting the repair of an injured neural circuit in zebrafish.

Key for the researchers’ success was the messenger molecule cAMP, which is produced by an enzyme called adenylyl cyclase. For their experiment, the scientist used a special form of this enzyme which is inducible by blue light. Using optogenetics, the scientists are able to specifically modulate the production of cAMP in cells expressing this enzyme by the use of blue light.

The researchers used this system in zebrafish larvae which had interrupted sensory lateralis nerves. These nerves normally communicate external sensory signals to the brain, but cannot normally repair after injury. “However, when blue light was shone on severed nerves that expressed a photoactivatable adenylyl cyclase, their repair was dramatically increased,” remembers PhD student Yan Xiao who is the first author of the study. “While untreated nerve terminals only made synapses again in five percent of the cases, about 30% did after photostimulation.” In simple terms: the scientists were able to stimulate the repair of a neuronal circuit by elevating cAMP with blue light.

“Optogenetics have revolutionized neurobiology, since the method has already been used to modify for instance the electrical activity of neurons. However, our results show for the first time how the repair of a complex neural circuit in a whole animal can be promoted remotely by the use of light”, explains López-Schier.

But the head of the study thinks that this is only the beginning: “Our results are a first step. Now we would like to investigate, whether these results can be extrapolated beyond single neurons in zebrafish, to more complex neuronal circuits of higher animals.” The scientist could think of using this method for future therapeutic approaches for the treatment of neuropathies like those occurring in the wake of Diabetes and other diseases.

Note: Material may have been edited for length and content. For further information, please contact the cited source.

Publication

Similar Stories On …

Link: http://www.neuroscientistnews.com

Fiberoptics, detail. Credit: davidgwynn / sxc.hu

Optogenetics: Harvesting the Power of Light for Neuronal Control

by Jeanene Swanson

With accolades like “method of the year” and “breakthrough of the decade,” it’s easy to assume that optogenetics—a scientific technique for turning neurons on and off using light—is, indeed, a game-changing technology. The technique has already shown promise for treating blindness,1 quieting seizures,2 and homing in on the genetic causes of brain disorders like Parkinson’s disease.3 It has also played a large role in enabling the NIH’s BRAIN Initiative, which aims to map the activity of every cell in the human brain. But, has it lived up to its hype? And what does the future hold for using optogenetics beyond simply studying how the brain works—can it also be useful in treating diseases as diverse as autism, PTSD, and depression?

The basics

Optogenetics uses light to control neurons that have been made artificially sensitive to illumination. In the lab, scientists employ viruses to introduce genes for light-sensitive proteins into neurons. First discovered in microbes, these naturally occurring proteins, called opsins, react to light. Some proteins react to light by turning neurons on, or prompting them to fire, while others turn off neuronal activity. In this way, optogenetics targets specific, modified neurons in order to discover their function and how they’re connected within larger neuronal networks.

In 2005, Dr. Karl Deisseroth, a bioengineering professor at Stanford University and a member of the Howard Hughes Medical Institute, and then-graduate students Dr. Edward Boyden (now at MIT) and Dr. Feng Zhang (now also at MIT), published the first paper demonstrating the use of microbial opsin genes to control neuronal activity.4 In 2010, Nature Methods named optogenetics “Method of the Year,”5 and Science called it one of several “Breakthroughs of the Decade.”6

Current approaches

Optogenetics has indeed, come a long way since 2005. Its most valuable feature as a cutting-edge neuroscience tool is that it offers an unmatched level of precision in its ability to affect a specific neuron at a specific time.

Opsin proteins come from bacterial or algal genomes, where they fulfill their roles as light-activated membrane ion channels. Opsin genes are introduced into specific neurons via transfection where a virus transfers both the gene and its promoter into the host cell’s genome. “Thousands of labs around the world are now using these optogenetic techniques, and thousands of papers have been published with these methods,” Deisseroth says.

There are many tools in use, including engineered opsins that can be targeted to single neurons, groups of neurons, and connections between regions of the brain. Modified opsins include those engineered to recognize different colors of light (red, blue, or yellow); those that are activated quickly or slowly; and those that simply turn neurons on or off, resulting in a binary circuit that has many futuristic applications such as altering memories. Opsin-targeting strategies, Deisseroth says, are also using specialized viruses that only insert the opsin gene into cells of interest. “A key moment was when we were able to solve the structure of the microbial channel opsin, which allowed us to engineer it at will.”7,8,9

Recently, Ed Boyden’s group at MIT developed a “fast” opsin called Chronos,10 as well as two more opsins that are sensitive to red light, Chrimson and Jaws,11 which activate and silence neurons respectively. It’s nice, Boyden notes, “because it goes deep in tissue,” reaching regions that were previously untouchable by standard fiberoptic tools consisting of lasers that send light to very small implanted optical fibers.12 “One of the obstacles to applying optogenetics is how to deliver light deep in the tissue or body,” Dr. Hiromu Yawo, a neuroscientist doing cutting-edge opsin engineering at Tohoku University, says. Fiber optic light sources are mainly used today; however, Deisseroth indicates that two-photon “spots” of light have been successfully used in living animals.

Challenges

When dreaming about the future of optogenetics, it’s important to consider that it is still early days. “We don’t have good maps of the brain, so using optogenetics is difficult for many scientific questions,” Boyden says. “We don’t often know where to stimulate.”

Activating deep brain tissue is also problematic. “As the visible light is absorbed by the tissue, the light sources have to be embedded in it for the optogenetic manipulation of deep tissue,” Yawo says. Infrared can go deep, but to date there is no opsin sensitive to this type of light. Additionally, viral vectors are difficult to apply to humans; neuronal selectivity depends on targeted promoters reaching their place in the genome. According to Yawo, these promoters are “mostly unidentified” in humans. “Even if identified, [the gene] is often too large to deliver efficiently or it is too weak to produce enough number of molecules to generate [a] response.”

There’s also cost. Says Deisseroth, “the main disadvantages include the light power requirements associated with targeting large numbers of individually specified cells. That requires fairly advanced and costly lasers.” However, standard optogenetics control is “actually relatively easy and cheap to do now, and we run training classes at Stanford to help people out in getting started,” he says.

Applications

While it has been mainly used as a way to study how individual neurons fire alone or in concert with other neurons or circuits of neurons, a slew of recent papers have helped elucidate pathways of many different diseases. For instance, research has demonstrated the use of optogenetics on D1 and D2 cells (types of dopamine receptors) in the striatum13 and subthalamic nucleus14 in mice, as a way to explore their role in Parkinson’s disease. Other work has involved finding what cells can be manipulated to alter fear memories, applicable to treating PTSD and other illnesses that revolve around conditioned fear responses;15elucidating neural networks involved in autism;16 and testing the causal link between dopamine expression and positive reinforcement in mental health disorders like addiction17and depression.18 Clinically, optogenetics could theoretically be used to treat diseases as diverse as Parkinson’s disease, PTSD, autism, schizophrenia, addiction, and depression, to name a few.

The future of optogenetics seems wide open. GenSight Biologics19, a company founded by leaders in the fields of ophthalmology and optogenetics, is aiming to use the technique to treat blindness caused by diseases resulting from cell loss in the retina, including glaucoma and retinal pigmentosa. Using optogenetics on other cell types has already gained some traction in research labs, with cardiac cells and stem cells being some of the prime non-neuronal targets. It’s also been adapted to study biochemical, instead of electrical, events, “opening the door to control of specific events in any cell in biology,” Deisseroth says. According to Yawo, events as diverse as “ionic microenvironment, signal transduction, enzymatic activity, and gene regulation are now under the targets of optogenetics.”

Optogenetics is being used in conjunction with other technologies too, to speed up the translation from lab to clinic. In a recent Science paper,20 scientists at the University of Geneva used a combination of deep brain stimulation—a proven tool to treat Parkinson’s disease—and a drug to block specific dopamine receptors to produce an “optogenetic-like” effect in lab mice. Ultimately, the mice’s cocaine use was reduced, underscoring the possibility of achieving the same effect in humans without having to solve the technological hurdles that applying optogenetics poses.

“The future is continued widespread use as a research tool,” Deisseroth says, to advance our still-small understanding of how individual neurons function in larger circuits. Indeed, when it comes to the brain, the whole is much greater than the sum of its parts, and optogenetics might be the best bet for probing not only deep, but far and wide.

Editor’s Note: Listen to Ed Boyden discuss his research in The Scientist’s on-demand webinar:New Models and Tools for Studying Synaptic Development and Function.

References

  1. Picaud S et al. (2013) Retinitis pigmentosa: eye sight restoration by optogenetic therapy. [Article in French] Biol Aujourdhui 207(2):109-121.
  2. Kullmann DM et al. (2012) Optogenetic and potassium channel gene therapy in a rodent model of focal neocortical epilepsy. Sci Transl Med 4(161):161ra152.
  3. Vazey EM, Aston-Jones G (2013) New tricks for old dogmas: optogenetic and designer receptor insights for Parkinson's disease. Brain Res 1511:153-163.
  4. Deisseroth K et al. (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8(9):1263-1268.
  5. Editorial (2011) Method of the Year 2010. Nat Methods 8(1).
  6. News Staff (2010) Insights of the decade. Stepping away from the trees for a look at the forest. Introduction. Science 330(6011):1612-1613.
  7. Staff (2012) Channelrhodopsin's crystal structure. Nat Methods 9(224).
  8. Deisseroth K et al. (2014) Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science 344(6182):420-424.
  9. Hegemann P et al. (2014) Conversion of Channelrhodopsin into a Light-Gated Chloride Channel. Science 344(6182):409-412.
  10. Boyden ES et al. (2014) Independent optical excitation of distinct neural populations. Nat Methods 11(3):338-346.
  11. Boyden ES et al. (2014) Noninvasive optical inhibition with a red-shifted microbial rhodopsin. Nat Neurosci (8):1123-1129.
  12. Deisseroth K et al. (2007) An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J Neural Eng 4(3):S143-156.
  13. Kreitzer AC et al. (2010) Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466:622–626
  14. Deisseroth K et al. (2009) Optical deconstruction of parkinsonian neural circuitry. Science 324(5925):354-359.
  15. Deisseroth K et al. (2011) Dynamics of Retrieval Strategies for Remote Memories. Cell 147(3):678-689.
  16. Deisseroth K et al. (2014) Natural neural projection dynamics underlying social behavior. Cell 157(7):1535-1551.
  17. Deisseroth K et al. (2011) Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement. Neuron 72(5):721-733.
  18. Deisseroth K et al. (2013) Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature 493(7433):537-541.
  19. GenSight http://www.gensight-biologics.com
  20. Creed M, Pascoli VJ, Lüscher C (2015) Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology. Science 347(6222):659-664.

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Link: http://www.neuroscientistnews.com

 

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Reptiles, emociones y cogniciones [1209]

de System Administrator - domingo, 19 de abril de 2015, 22:02
 

Reptiles, emociones y cogniciones

por Dr. Roberto Rosler

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Researchers create 'mini-brains' in lab to study neurological diseases [1670]

de System Administrator - lunes, 15 de febrero de 2016, 18:39
 

Researchers create 'mini-brains' in lab to study neurological diseases

February 12, 2016 | by NeuroScientistNews

Neurons (red) and astrocytes (green) derived from human neural stem cells growing in culture. Confocal micrograph.

Credit: Steven Pollard, Wellcome Images

Use of human-derived structures could allow for better research and reduce animal testing -

Researchers at the Johns Hopkins Bloomberg School of Public Health say they have developed tiny "mini-brains" made up of many of the neurons and cells of the human brain—and even some of its functionality—and which can be replicated on a large scale.

The researchers say that the creation of these "mini-brains," which will be discussed at the American Association for the Advancement of Science conference in Washington, DC, USA, on Feb. 12 at a press briefing and in a session on Feb. 13, could dramatically change how new drugs are tested for effectiveness and safety, taking the place of the hundreds of thousands of animals used for neurological scientific research in the United States. Performing research using these three-dimensional "mini-brains"—balls of brain cells that grow and form brain-like structures on their own over the course of eight weeks—should be superior to studying mice and rats because they are derived from human cells instead of rodents, they say.

See Also: Stem cells from teeth can make brain-like cells

"Ninety-five percent of drugs that look promising when tested in animal models fail once they are tested in humans at great expense of time and money," says study leader Thomas Hartung, MD, PhD, the Doerenkamp-Zbinden Professor and Chair for Evidence-based Toxicology at the Bloomberg School. "While rodent models have been useful, we are not 150-pound rats. And even though we are not balls of cells either, you can often get much better information from these balls of cells than from rodents.

"We believe that the future of brain research will include less reliance on animals, more reliance on human, cell-based models."

Hartung and his colleagues created the brains using induced pluripotent stem cells (iPSCs). These are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state and then are stimulated to grow into brain cells. Cells from the skin of several healthy adults were used to create the mini-brains, but Hartung says that cells from people with certain genetic traits or certain diseases can be used to create brains to study various types of pharmaceuticals. He says the brains can be used to study Alzheimer's disease, Parkinson's disease, multiple sclerosis and even autism. Projects to study viral infections, trauma and stroke have been started.

Hartung's mini-brains are very small—at 350 micrometers in diameter, or about the size of the eye of a housefly, they are just visible to the human eye—and hundreds to thousands of exact copies can be produced in each batch. One hundred of them can grow easily in the same petri dish in the lab. After cultivating the mini-brains for about two months, the brains developed four types of neurons and two types of support cells: astrocytes and oligodendrocytes, the latter of which go on to create myelin, which insulates the neuron's axons and allows them to communicate faster.

The researchers could watch the myelin developing and could see it begin to sheath the axons. The brains even showed spontaneous electrophysiological activity, which could be recorded with electrodes, similar to an electroencephalogram, (EEG). To test them, the researchers placed a mini-brain on an array of electrodes and listened to the spontaneous electrical communication of the neurons as test drugs were added.

Learn More: Stem cells in the brain: limited self-renewal

"We don't have the first brain model nor are we claiming to have the best one," says Hartung, who also directs the School's Center for Alternatives to Animal Testing.

"But this is the most standardized one. And when testing drugs, it is imperative that the cells being studied are as similar as possible to ensure the most comparable and accurate results."

Hartung is applying for a patent for the mini-brains and is also developing a commercial entity called ORGANOME to produce them. He hopes production can begin in 2016. He says they are easily reproducible and hopes to see them used by scientists in as many labs as possible. "Only when we can have brain models like this in any lab at any time will we be able to replace animal testing on a large scale," he says.

Link: http://www.neuroscientistnews.com

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Researchers generate a reference map of the human epigenome [1121]

de System Administrator - martes, 24 de febrero de 2015, 16:47
 

Researchers generate a reference map of the human epigenome

Better understanding of epigenetic modifications could elucidate their role in human traits, diseases.

by Helen Knight | MIT News correspondent 

The sequencing of the human genome laid the foundation for the study of genetic variation and its links to a wide range of diseases. But the genome itself is only part of the story, as genes can be switched on and off by a range of chemical modifications, known as “epigenetic marks.”

Now, a decade after the human genome was sequenced, the National Institutes of Health’s Roadmap Epigenomics Consortium has created a similar map of the human epigenome.

Manolis Kellis, a professor of computer science and a member of MIT’s Computer Science and Artificial Intelligence Laboratory and of the Broad Institute, led the effort to integrate and analyze the datasets produced by the project, which constitute the most comprehensive view of the human epigenome to date.

In a paper published today in the journal Nature, Kellis and his colleagues report 111 reference human epigenomes and study their regulatory circuitry, in a bid to understand their role in human traits and diseases.

“The consortium set out to systematically characterize the human epigenomic landscape, across diverse tissues and cell types,” Kellis says. “Given the enormity of the task, that meant bringing together multiple mapping centers and profiling a wide range of cell and tissue samples, to capture the diversity of the human epigenome.”

150 billion genomic sequences

The researchers generated 2,805 genome-wide datasets, encompassing a total of 150 billion sequencing reads, corresponding to 3,174-fold coverage of the human genome. These captured modifications of both the DNA itself, and of the histone proteins around which DNA is wrapped to form a structure known as chromatin.

Kellis and his team then developed and applied machine-learning algorithms that could translate these datasets into a reference map in each of the 111 cell types and tissues. The algorithms distinguished different classes of epigenomic modifications and used them to annotate the genomic regions active in each sample, and in particular regulatory elements that control where and when different genes are expressed.

“Different combinations of epigenetic marks characterize different regions of the genome, reflecting the specific functions that they play in each cell,” Kellis says. “By studying these combinations systematically, we can learn the language of the epigenome, and what it is telling us about both the activity and the function of each genomic region in each of the cell types.”

The researchers distinguished 15 different epigenomic signatures, or chromatin states, reflecting active, repressed, poised, transcribed, and inactive regions of the genome in each cell type. About 5 percent of each reference epigenome showed signatures associated with a regulatory function.

“Chromatin states allowed us to summarize the complexity of diverse epigenomic marks into a small number of common patterns,” Kellis says. “We could then interpret the biological functions of these patterns.”

Epigenomic dynamics

The researchers then studied how these chromatin states varied across different types of cells and tissues. This allowed them to group cell types with similar regulatory circuitry. They also grouped together regulatory regions that are active in the same types of cells. In this way they could begin to reveal the building blocks of regulatory circuits.

“Unlike the genome, which is mostly unchanged across cell types, the epigenome is extremely dynamic, reflecting the specialization of each cell type, such as neurons, heart, muscle, liver, skin, blood, or immune cells,” Kellis says. “By studying which regions turn on and off in the same cell types, we can gain insights into gene regulation.”

The researchers grouped 2 million predicted regulatory regions into 200 sets, or modules, which appeared to be acting in a coordinated manner across different types of cells. They found that 100 of these modules contained common sequence patterns, known as regulatory motifs, which may be responsible for their ability to work together in this way.

“Exploiting the predicted regulators and their motifs can help dissect the circuitry of different tissues and cells,” Kellis says.

The researchers also compared these epigenomic signatures with groups of genetic variants that are associated with different human traits and diseases. This allowed them to produce a map of the tissue and cell types that are most relevant to each trait or disease.

“We found that genetic variants are found in regulatory regions known as enhancers, which are activated only in certain types of cell and tissue,” Kellis says. “This suggests that many genetic variants affect the regulatory circuitry of the cell, possibly disrupting gene functions by altering tissue-specific gene expression levels.”

Tissue-specific enhancers affect 58 traits

The researchers found significant tissue-specific enhancer signatures for genetic variants associated with 58 different traits. These included height, in embryonic stem cells; multiple sclerosis, in immune cells; attention deficit disorder, in brain tissues; blood pressure, in heart tissues; fasting glucose, in pancreatic islets; cholesterol, in liver tissue; and Alzheimer’s disease, in CD14 monocytes.

“This unbiased view allows researchers to focus on relevant cells and tissues that may have been otherwise overlooked when studying a particular disease,” Kellis says. “The regulatory circuitry of a diverse range of cells can contribute to diseases that manifest in seemingly unexpected organs.”

Using these circuits to understand the molecular basis of human disorders will take many years and the effort of many labs, Kellis says. “Our results provide an invaluable map, and a rich set of hypotheses, which can help guide these studies.”

Wolf Reik, head of the epigenetics research program at the Babraham Institute in the U.K., who was not involved in the research, says the project is an exciting resource for the biomedical community worldwide.

“Important epigenetic marks were mapped systematically in many human cell types and tissues,” Reik says. “Integrative analysis of these epigenomes provides a global map toward understanding fundamental developmental and disease processes in humans.”

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Researchers Sharing Data Was Supposed to Change Science Forever. Did It? [1272]

de System Administrator - sábado, 27 de junio de 2015, 18:35
 

Researchers Sharing Data Was Supposed to Change Science Forever. Did It?

By Lily Hay Newman

In 2002, an article in the Washington Monthlyexplored a new trend called "open-source biology." It asked, "Can a band of biologists who share data freely out-innovate corporate researchers?"The basic idea: Instead of squirreling away their research so no one else could use it, scientists would pool their findings.

More than a decade later, open-source doesn't need to be in quotation marks, and the potential benefits of making scientific data freely available seem obvious.Plus, your tax dollars pay for a lot of it! But this week, researchers at the Defense Advanced Research Projects Agency's "Biology Is Technology" conference have a reality check to share: Open-source scientific data is grossly underutilized and kind of a mess.

Making scientific data open-source is a logical way to encourage interdisciplinary collaboration among researchers and democratize fields that are often stratified. It seems particularly exciting and promising when paired with big data—as computers have become powerful enough to process enormous data sets,the opportunity to make connections and draw conclusions seems irresistible.

And large data repositories have been the foundation of major biomedical discoveries and achievements. Joel Dudley, a biomedical informatics researcher at Mount Sinai, talked at the conference about a counterintuitive molecular similarity between skin disease and Alzheimer's that was discovered only because oflarge-scale data mapping. He also showed how broad access to patient medical histories and genotypes can reveal things like subpopulations within Type 2 diabetes patients in which each group is predisposed to have different types of conditions alongside diabetes.

The more data sets that are openly available, the more work like this can occur. But even something as potentially powerful as the open-source movement can be dead in the water if no one wants to engage with it. "Making data available to others is not sufficient to get people to work on it," said Stephen Friend, the president and co-founder of the nonprofit open-research organization Sage Bionetworks. Friend says that a big part of the problem is lack of incentives. Sure, building models to analyze and compare different datasets could produce meaningful results, but that takes time and other resources, and most of the work happens behind the scenes in obscurity.And scientists—well, they want a little glory.

One solution, which Sage is championing, is to create a sort of GitHub for biological data, called Synapse. GitHub is a Web-based code repository that offers project management and tracking tools for developers. Every time someone finalizes a change to code in GitHub, it's called a "commit," and when they push the change to the server, other people can see it in the project's history. The idea is that there's a log of which user was responsible for each change, however small, so everyone can see who is accountable for each decision. The flip side of commits is that when someone does something really smart, whether it's fixing a bug or adding new functionality to a program, everyone knows. Even if they're not responsible for the whole project, users can still publicly get credit for the good things they do.

Sage wants Synapse to work the same way. "The heart of it is an element of provenance," Friend said. The system tracks all different types of data organization and manipulation, and works to facilitate collaboration between disparate, even competing researchers by carefully recording who does what.

Another problem with open-source data is that it's often an unrecognizable hodgepodge of raw numbers from different experiments. "The hard thing is not actually to dump your data into the public domain," Peter Sorger, a systems biologist at Harvard, said at the DARPA event. "It’s to dump it in an intelligible way." Sorger estimates that to make data from a project usable, it takes about 20 percent of a researcher's total work. But "The incentive to do that? Zero," he said. "We have not created a system of incentives where the liberation of data is seen as critical."

If goodwill and curiosity aren't motivating researchers to work with open-source data on their own, there is still something that probably will: human limitation. "We have tiny little brains. We can’t understand the big stuff anymore," said Paul Cohen, a DARPA program manager in the Information and Innovation Office. "Machines will read the literature, machines will build complicated models, because frankly we can’t." When all you have to do is let your algorithms loose on a trove of publicly available data, there won't be any reason not to pull in everything that's out there. 

Future Tense is a partnership of SlateNew America, and Arizona State University.

Link: http://www.slate.com

 


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