Neuroscience  

Scientists have observed and measured synaptic transmission in a live animal for the first time, using optogenetics.

Neurons, the cells of the nervous system, communicate by transmitting chemical signals to each other through junctions called synapses. This "synaptic transmission" is critical for the brain and the spinal cord to quickly process the huge amount of incoming stimuli and generate outgoing signals.

Studying synaptic transmission in living animals is however very difficult, and researchers have to use artificial conditions that don't capture the real-life environment of neurons.

Now, scientists at the École Polytechnique Fédérale de Lausanne have observed and measured synaptic transmission in a live animal for the first time, using a new approach that combines genetics with the physics of light. Their breakthrough work is published in Neuron.

Aurélie Pala and Carl Petersen at EPFL's Brain Mind Institute used a novel technique, "optogenetics", that has been making significant inroads in the field of neuroscience in the past ten years. This method uses light to precisely control the activity of specific neurons in living, even moving, animals in real time. Such precision is critical in being able to study the hundreds of different neuron types, and understand higher brain functions such as thought, behavior, language, memory - or even mental disorders.

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Optogenetics works by inserting the gene of a light-sensitive protein into live neurons, from a single cell to an entire family of them. The genetically modified neurons then produce the light-sensitive protein, which sits on their outside, the membrane. There, it acts as an electrical channel - something like a gate. When light is shone on the neuron, the channel opens up and allows electrical ions to flow into the cell; a bit like a battery being charged by a solar cell.

The addition of electrical ions changes the voltage balance of the neuron, and if the optogenetic stimulus is sufficiently strong it generates an explosive electrical signal in the neuron. And that is the impact of optogenetics: controlling neuronal activity by switching a light on and off.

"This is a proof-of-concept study. Nonetheless, we think that we can use optogenetics to put together a larger picture of connectivity between other types of neurons in other areas of the brain."

Pala used optogenetics to stimulate single neurons of anesthetized mice and see if this approach could be used to record synaptic transmissions. The neurons she targeted were located in a part of the mouse's brain called the barrel cortex, which processes sensory information from the mouse's whiskers.

When Pala shone blue light on the neurons that contained the light-sensitive protein, the neurons activated and fired signals. At the same time, she measured electrical signals in neighboring neurons using microelectrodes that can record small voltage changes across a neuron's membrane.

Using these approaches, the researchers looked at how the light-sensitive neurons connected to some of their neighbors: small, connector neurons called "interneurons". In the brain, interneurons are usually inhibitory: when they receive a signal, they make the next neuron down the line less likely to continue the transmission.

The researchers recorded and analyzed synaptic transmissions from light-sensitive neurons to interneurons. In addition, they used an advanced imaging technique (two-photon microscopy) that allowed them to look deep into the brain of the live mouse and identify the type of each interneuron they were studying. The data showed that the neuronal transmissions from the light-sensitive neurons differed depending on the type of interneuron on the receiving end.

"This is a proof-of-concept study," says Aurélie Pala, who received her PhD for this work. "Nonetheless, we think that we can use optogenetics to put together a larger picture of connectivity between other types of neurons in other areas of the brain."

The scientists are now aiming to explore other neuronal connections in the mouse barrel cortex. They also want to try this technique on awake mice, to see how switching neuronal activity on and off with a light can affect higher brain functions.


SOURCE  École Polytechnique Fédérale de Lausanne via EurekAlert

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 Bionics  

A Danish man is the first amputee in the world to feel sensory rich information – in real-time – with a bionic hand wired to nerves in his upper arm. Using the Lifehand 2, Dennis Aabo Sørensen can grasp objects intuitively and identify what he is touching while blindfolded.

Nine years after an accident caused the loss of his left hand, Dennis Aabo Sørensen from Denmark became the first amputee in the world to feel – in real-time – with a sensory-enhanced bionic hand that was surgically wired to nerves in his upper arm.

Silvestro Micera and his team at EPFL (Switzerland) and SSSA (Italy) developed the revolutionary sensory feedback that allowed Sørensen to feel again while handling objects. A prototype of this bionic technology was tested in February 2013 during a clinical trial in Rome under the supervision of Paolo Maria Rossini at Gemelli Hospital (Italy). The study is published in Science Translational Medicine, and represents a collaboration called Lifehand 2 between several European universities and hospitals.

“The sensory feedback was incredible,” reports the 36 year-old amputee from Denmark. “I could feel things that I hadn’t been able to feel in over nine years.” In a laboratory setting wearing a blindfold and earplugs, Sørensen was able to detect how strongly he was grasping, as well as the shape and consistency of different objects he picked up with his prosthetic. “When I held an object, I could feel if it was soft or hard, round or square.”

Micera and his team enhanced the artificial hand with sensors that detect information about touch. This was done by measuring the tension in artificial tendons that control finger movement and turning this measurement into an electrical current. But this electrical signal is too coarse to be understood by the nervous system. Using computer algorithms, the scientists transformed the electrical signal into an impulse that sensory nerves can interpret. The sense of touch was achieved by sending the digitally refined signal through wires into four electrodes that were surgically implanted into what remains of Sørensen’s upper arm nerves.

“This is the first time in neuroprosthetics that sensory feedback has been restored and used by an amputee in real-time to control an artificial limb,” says Micera.

“We were worried about reduced sensitivity in Dennis’ nerves since they hadn’t been used in over nine years,” says Stanisa Raspopovic, first author and scientist at EPFL and SSSA. These concerns faded away as the scientists successfully reactivated Sørensen’s sense of touch.

Image Source - © LifeHand 2 / Patrizia Tocci

A year ago, Sørensen underwent surgery in Rome at Gemelli Hospital. A specialized group of surgeons and neurologists, led by Paolo Maria Rossini, implanted transneural electrodes into the ulnar and median nerves of Sørensen’s left arm. After 19 days of preliminary tests, Micera and his team connected their prosthetic to the electrodes – and to Sørensen – every day for an entire week.

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The ultra-thin, ultra-precise electrodes, developed by Thomas Stieglitz’s research group at Freiburg University  in Germany, made it possible to relay extremely weak electrical signals directly into the nervous system. A tremendous amount of preliminary research was done to ensure that the electrodes would continue to work even after the formation of post-surgery scar tissue. It is also the first time that such electrodes have been transversally implanted into the peripheral nervous system of an amputee.

The clinical study provides the first step towards a bionic hand, although a sensory-enhanced prosthetic is years away from being commercially available and the bionic hand of science fiction movies is even further away.

The next step involves miniaturizing the sensory feedback electronics for a portable prosthetic. In addition, the scientists will fine-tune the sensory technology for better touch resolution and increased awareness about the angular movement of fingers.

The electrodes were removed from Sørensen’s arm after one month due to safety restrictions imposed on clinical trials, although the scientists are optimistic that they could remain implanted and functional without damage to the nervous system for many years.

Image Source - © LifeHand 2 / Patrizia Tocci

Sørensen’s psychological strength was an asset for the clinical study. He says, “I was more than happy to volunteer for the clinical trial, not only for myself, but to help other amputees as well.” Now he faces the challenge of having experienced touch again for only a short period of time.

Sørensen lost his left hand while handling fireworks during a family holiday. He was rushed to the hospital where his hand was immediately amputated. Since then, he has been wearing a commercial prosthetic that detects muscle movement in his stump, allowing him to open and close his hand, and hold onto objects.




SOURCE  EPFL

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 Avatar Research  

Researchers from the Center for Neuroprosthetics at the Swiss Federal Institute of Technology (EPFL), Switzerland, show that people can be "tricked" into feeling that an image of a human figure -- an "avatar" -- is their own body.

Researchers from the Center for Neuroprosthetics at the Swiss Federal Institute of Technology (EPFL), Switzerland, show that people can be "tricked" into feeling that an image of a human figure -- an "avatar" -- is their own body.

The study is published in the open-access journal Frontiers in Behavioral Neuroscience.

Twenty-two volunteers underwent a Full Body Illusion when they were stroked with a robotic device system while they watched an avatar being stroked in the same spot. The study is the first to demonstrate that Full Body Illusions can be accompanied by changes in body temperature.

Participants wore a 3D high-resolution head-mounted display to view the avatar from behind. They were then subjected to 40 seconds of stroking by a robot, on either their left or right back or on their left or right leg. Meanwhile, they were shown a red dot that moved synchronously on the same regions of the avatar (see image below).

Image Source: Roy Salomon et al (2013) Frontiers in Behavioral Neuroscience

After the stroking, the participants were prompted to imagine dropping a ball and to signal the moment when they felt that the ball would hit the floor. This allowed the researchers to objectively measure where the participants perceived their body to be.

The volunteers were asked questions about how much they identified with the avatar and where they felt the stroking originated from. Furthermore, to test for physiological changes during the illusion, the participants' skin temperature was measured on four locations on the back and legs across 20 time points.

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Results showed that stroking the same body part simultaneously on the real body and the avatar induced a Full Body Illusion. The volunteers were confused as to where their body was and they partly identified with the avatar. More than 70% of participants felt that the touch they had felt on their body was derived from the stroking seen on the avatar.

Data revealed a continuous widespread decrease in skin temperature that was not specific to the site of measurement and showed similar effects in all locations. The changes in body temperature "were highly significant, but very small," write the authors in the study, adding that the decrease was in the range of 0.006-0.014 degrees Celsius.

The recorded temperature change was smaller than an earlier study found (0.24 degrees Celsius) that looked at fluctuations during rubber hand illusion, probably because the latter used a hand-held thermometer over longer periods and different regions of the body, the authors explain.

"When the brain is confronted with a multisensory conflict, such as that produced by the Full Body Illusion, the way we perceive our real body changes. This causes a decrease in our body temperature, " says Dr. Roy Salomon, a postdoctoral fellow at the EPFL and the lead author of the study.

The scientists also say that the field of cognitive neuroprosthetics carries great promise for new prosthetics that are based on a scientific understanding of the link between body and mind.

"This study helps us to understand the brain mechanisms that underlie the bodily aspects of consciousness and idea of 'self'. It may contribute to the design of novel prosthetic devices and treatment of pain, for example, after stroke, amputation, or tetraplegia," says Prof. Olaf Blanke, director of the newly founded Center for Neuroprosthetics.

"This type of research may also help to understand and treat psychiatric disorders, such as schizophrenia and depression. We hope that by identifying the mechanisms involved in these processes and how they are altered in psychosis we can help these patients," adds Dr. Salomon.



SOURCE  Science Daily
Images: Roy Salomon et al (2013) Frontiers in Behavioral Neuroscience

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