Tag Archives: neurons

What is a multiregional brain-on-a-chip?

In response to having created a multiregional brain-on-a-chip, there’s an explanation from the team at Harvard University (which answers my question) in a Jan. 13, 2017 Harvard John A. Paulson School of Engineering and Applied Sciences news release (also on EurekAlert) by Leah Burrows,

Harvard University researchers have developed a multiregional brain-on-a-chip that models the connectivity between three distinct regions of the brain. The in vitro model was used to extensively characterize the differences between neurons from different regions of the brain and to mimic the system’s connectivity.

“The brain is so much more than individual neurons,” said Ben Maoz, co-first author of the paper and postdoctoral fellow in the Disease Biophysics Group in the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). “It’s about the different types of cells and the connectivity between different regions of the brain. When modeling the brain, you need to be able to recapitulate that connectivity because there are many different diseases that attack those connections.”

“Roughly twenty-six percent of the US healthcare budget is spent on neurological and psychiatric disorders,” said Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics Building at SEAS and Core Faculty Member of the Wyss Institute for Biologically Inspired Engineering at Harvard University. “Tools to support the development of therapeutics to alleviate the suffering of these patients is not only the human thing to do, it is the best means of reducing this cost.”

Researchers from the Disease Biophysics Group at SEAS and the Wyss Institute modeled three regions of the brain most affected by schizophrenia — the amygdala, hippocampus and prefrontal cortex.

They began by characterizing the cell composition, protein expression, metabolism, and electrical activity of neurons from each region in vitro.

“It’s no surprise that neurons in distinct regions of the brain are different but it is surprising just how different they are,” said Stephanie Dauth, co-first author of the paper and former postdoctoral fellow in the Disease Biophysics Group. “We found that the cell-type ratio, the metabolism, the protein expression and the electrical activity all differ between regions in vitro. This shows that it does make a difference which brain region’s neurons you’re working with.”

Next, the team looked at how these neurons change when they’re communicating with one another. To do that, they cultured cells from each region independently and then let the cells establish connections via guided pathways embedded in the chip.

The researchers then measured cell composition and electrical activity again and found that the cells dramatically changed when they were in contact with neurons from different regions.

“When the cells are communicating with other regions, the cellular composition of the culture changes, the electrophysiology changes, all these inherent properties of the neurons change,” said Maoz. “This shows how important it is to implement different brain regions into in vitro models, especially when studying how neurological diseases impact connected regions of the brain.”

To demonstrate the chip’s efficacy in modeling disease, the team doped different regions of the brain with the drug Phencyclidine hydrochloride — commonly known as PCP — which simulates schizophrenia. The brain-on-a-chip allowed the researchers for the first time to look at both the drug’s impact on the individual regions as well as its downstream effect on the interconnected regions in vitro.

The brain-on-a-chip could be useful for studying any number of neurological and psychiatric diseases, including drug addiction, post traumatic stress disorder, and traumatic brain injury.

“To date, the Connectome project has not recognized all of the networks in the brain,” said Parker. “In our studies, we are showing that the extracellular matrix network is an important part of distinguishing different brain regions and that, subsequently, physiological and pathophysiological processes in these brain regions are unique. This advance will not only enable the development of therapeutics, but fundamental insights as to how we think, feel, and survive.”

Here’s an image from the researchers,

Caption: Image of the in vitro model showing three distinct regions of the brain connected by axons. Credit: Disease Biophysics Group/Harvard University

Here’s a link to and a citation for the paper,

Neurons derived from different brain regions are inherently different in vitro: A novel multiregional brain-on-a-chip by Stephanie Dauth, Ben M Maoz, Sean P Sheehy, Matthew A Hemphill, Tara Murty, Mary Kate Macedonia, Angie M Greer, Bogdan Budnik, Kevin Kit Parker. Journal of Neurophysiology Published 28 December 2016 Vol. no. [?] , DOI: 10.1152/jn.00575.2016

This paper is behind a paywall and they haven’t included the vol. no. in the citation I’ve found.

Using melanin in bioelectronic devices

Brazilian researchers are working with melanin to make biosensors and other bioelectronic devices according to a Dec. 20, 2016 news item on phys.org,

Bioelectronics, sometimes called the next medical frontier, is a research field that combines electronics and biology to develop miniaturized implantable devices capable of altering and controlling electrical signals in the human body. Large corporations are increasingly interested: a joint venture in the field has recently been announced by Alphabet, Google’s parent company, and pharmaceutical giant GlaxoSmithKline (GSK).

One of the challenges that scientists face in developing bioelectronic devices is identifying and finding ways to use materials that conduct not only electrons but also ions, as most communication and other processes in the human organism use ionic biosignals (e.g., neurotransmitters). In addition, the materials must be biocompatible.

Resolving this challenge is one of the motivations for researchers at São Paulo State University’s School of Sciences (FC-UNESP) at Bauru in Brazil. They have succeeded in developing a novel route to more rapidly synthesize and to enable the use of melanin, a polymeric compound that pigments the skin, eyes and hair of mammals and is considered one of the most promising materials for use in miniaturized implantable devices such as biosensors.

A Dec. 14, 2016 FAPESP (São Paulo Research Foundation) press release, which originated the news item, further describes both the research and a recent meeting where the research was shared (Note: A link has been removed),

Some of the group’s research findings were presented at FAPESP Week Montevideo during a round-table session on materials science and engineering.

The symposium was organized by the Montevideo Group Association of Universities (AUGM), Uruguay’s University of the Republic (UdelaR) and FAPESP and took place on November 17-18 at UdelaR’s campus in Montevideo. Its purpose was to strengthen existing collaborations and establish new partnerships among South American scientists in a range of knowledge areas. Researchers and leaders of institutions in Uruguay, Brazil, Argentina, Chile and Paraguay attended the meeting.

“All the materials that have been tested to date for applications in bioelectronics are entirely synthetic,” said Carlos Frederico de Oliveira Graeff, a professor at UNESP Bauru and principal investigator for the project, in an interview given to Agência FAPESP.

“One of the great advantages of melanin is that it’s a totally natural compound and biocompatible with the human body: hence its potential use in electronic devices that interface with brain neurons, for example.”

Application challenges

According to Graeff, the challenges of using melanin as a material for the development of bioelectronic devices include the fact that like other carbon-based materials, such as graphene, melanin is not easily dispersible in an aqueous medium, a characteristic that hinders its application in thin-film production.

Furthermore, the conventional process for synthesizing melanin is complex: several steps are hard to control, it can last up to 56 days, and it can result in disorderly structures.

In a series of studies performed in recent years at the Center for Research and Development of Functional Materials (CDFM), where Graeff is a leading researcher and which is one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP, he and his collaborators managed to obtain biosynthetic melanin with good dispersion in water and a strong resemblance to natural melanin using a novel synthesis route.

The process developed by the group at CDMF takes only a few hours and is based on changes in parameters such as temperature and the application of oxygen pressure to promote oxidation of the material.

By applying oxygen pressure, the researchers were able to increase the density of carboxyl groups, which are organic functional groups consisting of a carbon atom double bonded to an oxygen atom and single bonded to a hydroxyl group (oxygen + hydrogen). This enhances solubility and facilitates the suspension of biosynthetic melanin in water.

“The production of thin films of melanin with high homogeneity and quality is made far easier by these characteristics,” Graeff said.

By increasing the density of carboxyl groups, the researchers were also able to make biosynthetic melanin more similar to the biological compound.

In living organisms, an enzyme that participates in the synthesis of melanin facilitates the production of carboxylic acids. The new melanin synthesis route enabled the researchers to mimic the role of this enzyme chemically while increasing carboxyl group density.

“We’ve succeeded in obtaining a material that’s very close to biological melanin by chemical synthesis and in producing high-quality film for use in bioelectronic devices,” Graeff said.

Through collaboration with colleagues at research institutions in Canada [emphasis mine], the Brazilian researchers have begun using the material in a series of applications, including electrical contacts, pH sensors and photovoltaic cells.

More recently, they have embarked on an attempt to develop a transistor, a semiconductor device used to amplify or switch electronic signals and electrical power.

“Above all, we aim to produce transistors precisely in order to enhance this coupling of electronics with biological systems,” Graeff said.

I’m glad to have gotten some information about the work in South America. It’s one of FrogHeart’s shortcomings that I have so little about the research in that area of the world. I believe this is largely due to my lack of Spanish language skills. Perhaps one day there’ll be a universal translator that works well. In the meantime, it was a surprise to see Canada mentioned in this piece. I wonder which Canadian research institutions are involved with this research in South America.

Changing synaptic connectivity with a memristor

The French have announced some research into memristive devices that mimic both short-term and long-term neural plasticity according to a Dec. 6, 2016 news item on Nanowerk,

Leti researchers have demonstrated that memristive devices are excellent candidates to emulate synaptic plasticity, the capability of synapses to enhance or diminish their connectivity between neurons, which is widely believed to be the cellular basis for learning and memory.

The breakthrough was presented today [Dec. 6, 2016] at IEDM [International Electron Devices Meeting] 2016 in San Francisco in the paper, “Experimental Demonstration of Short and Long Term Synaptic Plasticity Using OxRAM Multi k-bit Arrays for Reliable Detection in Highly Noisy Input Data”.

Neural systems such as the human brain exhibit various types and time periods of plasticity, e.g. synaptic modifications can last anywhere from seconds to days or months. However, prior research in utilizing synaptic plasticity using memristive devices relied primarily on simplified rules for plasticity and learning.

The project team, which includes researchers from Leti’s sister institute at CEA Tech, List, along with INSERM and Clinatec, proposed an architecture that implements both short- and long-term plasticity (STP and LTP) using RRAM devices.

A Dec. 6, 2016 Laboratoire d’électronique des technologies de l’information (LETI) press release, which originated the news item, elaborates,

“While implementing a learning rule for permanent modifications – LTP, based on spike-timing-dependent plasticity – we also incorporated the possibility of short-term modifications with STP, based on the Tsodyks/Markram model,” said Elisa Vianello, Leti non-volatile memories and cognitive computing specialist/research engineer. “We showed the benefits of utilizing both kinds of plasticity with visual pattern extraction and decoding of neural signals. LTP allows our artificial neural networks to learn patterns, and STP makes the learning process very robust against environmental noise.”

Resistive random-access memory (RRAM) devices coupled with a spike-coding scheme are key to implementing unsupervised learning with minimal hardware footprint and low power consumption. Embedding neuromorphic learning into low-power devices could enable design of autonomous systems, such as a brain-machine interface that makes decisions based on real-time, on-line processing of in-vivo recorded biological signals. Biological data are intrinsically highly noisy and the proposed combined LTP and STP learning rule is a powerful technique to improve the detection/recognition rate. This approach may enable the design of autonomous implantable devices for rehabilitation purposes

Leti, which has worked on RRAM to develop hardware neuromorphic architectures since 2010, is the coordinator of the H2020 [Horizon 2020] European project NeuRAM3. That project is working on fabricating a chip with architecture that supports state-of-the-art machine-learning algorithms and spike-based learning mechanisms.

That’s it folks.

Getting your brain cells to glow in the dark

The extraordinary effort to colonize our brains continues apace with a new sensor from Vanderbilt University. From an Oct. 27, 2016 news item on ScienceDaily,

A new kind of bioluminescent sensor causes individual brain cells to imitate fireflies and glow in the dark.

The probe, which was developed by a team of Vanderbilt scientists, is a genetically modified form of luciferase, the enzyme that a number of other species including fireflies use to produce light. …

The scientists created the technique as a new and improved method for tracking the interactions within large neural networks in the brain.

“For a long time neuroscientists relied on electrical techniques for recording the activity of neurons. These are very good at monitoring individual neurons but are limited to small numbers of neurons. The new wave is to use optical techniques to record the activity of hundreds of neurons at the same time,” said Carl Johnson, Stevenson Professor of Biological Sciences, who headed the effort.

Individual neuron glowing with bioluminescent light produced by a new genetically engineered sensor. (Johnson Lab / Vanderbilt University)

Individual neuron glowing with bioluminescent light produced by a new genetically engineered sensor. (Johnson Lab / Vanderbilt University)

An Oct. 27, 2016 Vanderbilt University news release (also on EurekAlert) by David Salisbury, which originated the news item, explains the work in more detail,

“Most of the efforts in optical recording use fluorescence, but this requires a strong external light source which can cause the tissue to heat up and can interfere with some biological processes, particularly those that are light sensitive,” he [Carl Johnson] said.

Based on their research on bioluminescence in “a scummy little organism, the green alga Chlamydomonas, that nobody cares much about” Johnson and his colleagues realized that if they could combine luminescence with optogenetics – a new biological technique that uses light to control cells, particularly neurons, in living tissue – they could create a powerful new tool for studying brain activity.

“There is an inherent conflict between fluorescent techniques and optogenetics. The light required to produce the fluorescence interferes with the light required to control the cells,” said Johnson. “Luminescence, on the other hand, works in the dark!”

Johnson and his collaborators – Associate Professor Donna Webb, Research Assistant Professor Shuqun Shi, post-doctoral student Jie Yang and doctoral student Derrick Cumberbatch in biological sciences and Professor Danny Winder and postdoctoral student Samuel Centanni in molecular physiology and biophysics – genetically modified a type of luciferase obtained from a luminescent species of shrimp so that it would light up when exposed to calcium ions. Then they hijacked a virus that infects neurons and attached it to their sensor molecule so that the sensors are inserted into the cell interior.

The researchers picked calcium ions because they are involved in neuron activation. Although calcium levels are high in the surrounding area, normally they are very low inside the neurons. However, the internal calcium level spikes briefly when a neuron receives an impulse from one of its neighbors.

They tested their new calcium sensor with one of the optogenetic probes (channelrhodopsin) that causes the calcium ion channels in the neuron’s outer membrane to open, flooding the cell with calcium. Using neurons grown in culture they found that the luminescent enzyme reacted visibly to the influx of calcium produced when the probe was stimulated by brief light flashes of visible light.

To determine how well their sensor works with larger numbers of neurons, they inserted it into brain slices from the mouse hippocampus that contain thousands of neurons. In this case they flooded the slices with an increased concentration of potassium ions, which causes the cell’s ion channels to open. Again, they found that the sensor responded to the variations in calcium concentrations by brightening and dimming.

“We’ve shown that the approach works,” Johnson said. “Now we have to determine how sensitive it is. We have some indications that it is sensitive enough to detect the firing of individual neurons, but we have to run more tests to determine if it actually has this capability.”

Here’s a link to and a citation for the paper,

Coupling optogenetic stimulation with NanoLuc-based luminescence (BRET) Ca++ sensing by Jie Yang, Derrick Cumberbatch, Samuel Centanni, Shu-qun Shi, Danny Winder, Donna Webb, & Carl Hirschie Johnson. Nature Communications 7, Article number: 13268 (2016)  doi:10.1038/ncomms13268 Published online: 27 October 2016

This paper is open access.

Stretchy optical materials for implants that could pulse light

An Oct. 17, 2016 Massachusetts Institute of Technology (MIT) news release (also on EurekAlert) by Emily Chu describes research that could lead to long-lasting implants offering preventive health strategies,

Researchers from MIT and Harvard Medical School have developed a biocompatible and highly stretchable optical fiber made from hydrogel — an elastic, rubbery material composed mostly of water. The fiber, which is as bendable as a rope of licorice, may one day be implanted in the body to deliver therapeutic pulses of light or light up at the first sign of disease. [emphasis mine]

The researchers say the fiber may serve as a long-lasting implant that would bend and twist with the body without breaking down. The team has published its results online in the journal Advanced Materials.

Using light to activate cells, and particularly neurons in the brain, is a highly active field known as optogenetics, in which researchers deliver short pulses of light to targeted tissues using needle-like fibers, through which they shine light from an LED source.

“But the brain is like a bowl of Jell-O, whereas these fibers are like glass — very rigid, which can possibly damage brain tissues,” says Xuanhe Zhao, the Robert N. Noyce Career Development Associate Professor in MIT’s Department of Mechanical Engineering. “If these fibers could match the flexibility and softness of the brain, they could provide long-term more effective stimulation and therapy.”

Getting to the core of it

Zhao’s group at MIT, including graduate students Xinyue Liu and Hyunwoo Yuk, specializes in tuning the mechanical properties of hydrogels. The researchers have devised multiple recipes for making tough yet pliable hydrogels out of various biopolymers. The team has also come up with ways to bond hydrogels with various surfaces such as metallic sensors and LEDs, to create stretchable electronics.

The researchers only thought to explore hydrogel’s use in optical fibers after conversations with the bio-optics group at Harvard Medical School, led by Associate Professor Seok-Hyun (Andy) Yun. Yun’s group had previously fabricated an optical fiber from hydrogel material that successfully transmitted light through the fiber. However, the material broke apart when bent or slightly stretched. Zhao’s hydrogels, in contrast, could stretch and bend like taffy. The two groups joined efforts and looked for ways to incorporate Zhao’s hydrogel into Yun’s optical fiber design.

Yun’s design consists of a core material encased in an outer cladding. To transmit the maximum amount of light through the core of the fiber, the core and the cladding should be made of materials with very different refractive indices, or degrees to which they can bend light.

“If these two things are too similar, whatever light source flows through the fiber will just fade away,” Yuk explains. “In optical fibers, people want to have a much higher refractive index in the core, versus cladding, so that when light goes through the core, it bounces off the interface of the cladding and stays within the core.”

Happily, they found that Zhao’s hydrogel material was highly transparent and possessed a refractive index that was ideal as a core material. But when they tried to coat the hydrogel with a cladding polymer solution, the two materials tended to peel apart when the fiber was stretched or bent.

To bond the two materials together, the researchers added conjugation chemicals to the cladding solution, which, when coated over the hydrogel core, generated chemical links between the outer surfaces of both materials.

“It clicks together the carboxyl groups in the cladding, and the amine groups in the core material, like molecular-level glue,” Yuk says.

Sensing strain

The researchers tested the optical fibers’ ability to propagate light by shining a laser through fibers of various lengths. Each fiber transmitted light without significant attenuation, or fading. They also found that fibers could be stretched over seven times their original length without breaking.

Now that they had developed a highly flexible and robust optical fiber, made from a hydrogel material that was also biocompatible, the researchers began to play with the fiber’s optical properties, to see if they could design a fiber that could sense when and where it was being stretched.

They first loaded a fiber with red, green, and blue organic dyes, placed at specific spots along the fiber’s length. Next, they shone a laser through the fiber and stretched, for instance, the red region. They measured the spectrum of light that made it all the way through the fiber, and noted the intensity of the red light. They reasoned that this intensity relates directly to the amount of light absorbed by the red dye, as a result of that region being stretched.

In other words, by measuring the amount of light at the far end of the fiber, the researchers can quantitatively determine where and by how much a fiber was stretched.

“When you stretch a certain portion of the fiber, the dimensions of that part of the fiber changes, along with the amount of light that region absorbs and scatters, so in this way, the fiber can serve as a sensor of strain,” Liu explains.

“This is like a multistrain sensor through a single fiber,” Yuk adds. “So it can be an implantable or wearable strain gauge.”

The researchers imagine that such stretchable, strain-sensing optical fibers could be implanted or fitted along the length of a patient’s arm or leg, to monitor for signs of improving mobility.

Zhao envisions the fibers may also serve as sensors, lighting up in response to signs of disease.

“We may be able to use optical fibers for long-term diagnostics, to optically monitor tumors or inflammation,” he says. “The applications can be impactful.”

Here’s a link to and a citation for the paper,

Highly Stretchable, Strain Sensing Hydrogel Optical Fibers by Jingjing Guo, Xinyue Liu, Nan Jiang, Ali K. Yetisen, Hyunwoo Yuk, Changxi Yang, Ali Khademhosseini, Xuanhe Zhao, and Seok-Hyun Yun. Advanced Materials DOI: 10.1002/adma.201603160 Version of Record online: 7 OCT 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

A bionic hybrid neurochip from the University of Calgary (Canada)

The University of Calgary is publishing some very exciting work these days as can be seen in my Sept. 21, 2016 posting about quantum teleportation. Today, the university announced this via an Oct. 26, 2016 news item on Nanowerk (Note: A link has been removed),

Brain functions are controlled by millions of brain cells. However, in order to understand how the brain controls functions, such as simple reflexes or learning and memory, we must be able to record the activity of large networks and groups of neurons. Conventional methods have allowed scientists to record the activity of neurons for minutes, but a new technology, developed by University of Calgary researchers, known as a bionic hybrid neuro chip, is able to record activity in animal brain cells for weeks at a much higher resolution. The technological advancement was published in the journal Scientific Reports(“A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording”).

There’s more from an Oct. 26, 2016 University of Calgary news release on EurekAlert, which originated the news item,

“These chips are 15 times more sensitive than conventional neuro chips,” says Naweed Syed, PhD, scientific director of the University of Calgary, Cumming School of Medicine’s Alberta Children’s Hospital Research Institute, member of the Hotchkiss Brain Institute and senior author on the study. “This allows brain cell signals to be amplified more easily and to see real time recordings of brain cell activity at a resolution that has never been achieved before.”

The development of this technology will allow researchers to investigate and understand in greater depth, in animal models, the origins of neurological diseases and conditions such as epilepsy, as well as other cognitive functions such as learning and memory.

“Recording this activity over a long period of time allows you to see changes that occur over time, in the activity itself,” says Pierre Wijdenes, a PhD student in the Biomedical Engineering Graduate Program and the study’s first author. “This helps to understand why certain neurons form connections with each other and why others won’t.”

The cross-faculty team created the chip to mimic the natural biological contact between brain cells, essentially tricking the brain cells into believing that they are connecting with other brain cells. As a result, the cells immediately connect with the chip, thereby allowing researchers to view and record the two-way communication that would go on between two normal functioning brain cells.

“We simulated what mother-nature does in nature and provided brain cells with an environment where they feel as if they are at home,” says Syed. “This has allowed us to increase the sensitivity of our readings and help neurons build a long-term relationship with our electronic chip.”

While the chip is currently used to analyze animal brain cells, this increased resolution and the ability to make long-term recordings is bringing the technology one step closer to being effective in the recording of human brain cell activity.

“Human brain cell signals are smaller and therefore require more sensitive electronic tools to be designed to pick up the signals,” says Colin Dalton, Adjunct Professor in the Department of Electrical and Computer Engineering at the Schulich School of Engineering and a co-author on this study. Dalton is also the Facility Manager of the University of Calgary’s Advanced Micro/nanosystems Integration Facility (AMIF), where the chips were designed and fabricated.

Researchers hope the technology will one day be used as a tool to bring personalized therapeutic options to patients facing neurological disease.

Here’s a link to and a citation for the paper,

A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording by Pierre Wijdenes, Hasan Ali, Ryden Armstrong, Wali Zaidi, Colin Dalton & Naweed I. Syed. Scientific Reports 6, Article number: 34553 (2016) doi:10.1038/srep34553
Published online: 12 October 2016

This paper is  open access.

Nanotubes tunnel between neurons in Parkinson’s disease

An Aug. 22, 2016 news item on ScienceDaily describes how scientists from the Institut Pasteur (France) have developed insight into one of the processes in Parkinson’s disease,

Scientists have demonstrated the role of lysosomal vesicles in transporting alpha-synuclein aggregates, responsible for Parkinson’s and other neurodegenerative diseases, between neurons. These proteins move from one neuron to the next in lysosomal vesicles which travel along the ‘tunneling nanotubes’ between cells.

An Aug. 22, 2016 Institut Pasteur press release (also on EurekAlert), expands on the theme,

Synucleinopathies, a group of neurodegenerative diseases including Parkinson’s disease, are characterized by the pathological deposition of aggregates of the misfolded α-synuclein protein into inclusions throughout the central and peripheral nervous system. Intercellular propagation (from one neuron to the next) of α-synuclein aggregates contributes to the progression of the neuropathology, but little was known about the mechanism by which spread occurs.

In this study, scientists from the Membrane Traffic and Pathogenesis Unit, directed by Chiara Zurzolo at the Institut Pasteur, used fluorescence microscopy to demonstrate that pathogenic α-synuclein fibrils travel between neurons in culture, inside lysosomal vesicles through tunneling nanotubes (TNTs), a new mechanism of intercellular communication.

After being transferred via TNTs, α-synuclein fibrils are able to recruit and induce aggregation of the soluble α-synuclein protein in the cytosol of cells receiving the fibrils, thus explaining the propagation of the disease. The scientists propose that cells overloaded with α-synuclein aggregates in lysosomes dispose of this material by hijacking TNT-mediated intercellular trafficking. However, this results in the disease being spread to naive neurons.

This study demonstrates that TNTs play a significant part in the intercellular transfer of α-synuclein fibrils and reveals the specific role of lysosomes in this process. This represents a major breakthrough in understanding the mechanisms underlying the progression of synucleinopathies.

These compelling findings, together with previous reports from the same team, point to the general role of TNTs in the propagation of prion-like proteins in neurodegenerative diseases and identify TNTs as a new therapeutic target to combat the progression of these incurable diseases.

Here’s a link to and a citation for the paper,

Tunneling nanotubes spread fibrillar α‐synuclein by intercellular trafficking of lysosomes by Saïda Abounit, Luc Bousset, Frida Loria, Seng Zhu, Fabrice de Chaumont, Laura Pieri, Jean-Christophe Olivo-Marin, Ronald Melki, Chiara Zurzolo. The EMBO Journal (2016) e201593411 DOI 10.15252/embj.201593411 Published online 22.08.2016

This paper is behind a paywall.

US white paper on neuromorphic computing (or the nanotechnology-inspired Grand Challenge for future computing)

The US has embarked on a number of what is called “Grand Challenges.” I first came across the concept when reading about the Bill and Melinda Gates (of Microsoft fame) Foundation. I gather these challenges are intended to provide funding for research that advances bold visions.

There is the US National Strategic Computing Initiative established on July 29, 2015 and its first anniversary results were announced one year to the day later. Within that initiative a nanotechnology-inspired Grand Challenge for Future Computing was issued and, according to a July 29, 2016 news item on Nanowerk, a white paper on the topic has been issued (Note: A link has been removed),

Today [July 29, 2016), Federal agencies participating in the National Nanotechnology Initiative (NNI) released a white paper (pdf) describing the collective Federal vision for the emerging and innovative solutions needed to realize the Nanotechnology-Inspired Grand Challenge for Future Computing.

The grand challenge, announced on October 20, 2015, is to “create a new type of computer that can proactively interpret and learn from data, solve unfamiliar problems using what it has learned, and operate with the energy efficiency of the human brain.” The white paper describes the technical priorities shared by the agencies, highlights the challenges and opportunities associated with these priorities, and presents a guiding vision for the research and development (R&D) needed to achieve key technical goals. By coordinating and collaborating across multiple levels of government, industry, academia, and nonprofit organizations, the nanotechnology and computer science communities can look beyond the decades-old approach to computing based on the von Neumann architecture and chart a new path that will continue the rapid pace of innovation beyond the next decade.

A July 29, 2016 US National Nanotechnology Coordination Office news release, which originated the news item, further and succinctly describes the contents of the paper,

“Materials and devices for computing have been and will continue to be a key application domain in the field of nanotechnology. As evident by the R&D topics highlighted in the white paper, this challenge will require the convergence of nanotechnology, neuroscience, and computer science to create a whole new paradigm for low-power computing with revolutionary, brain-like capabilities,” said Dr. Michael Meador, Director of the National Nanotechnology Coordination Office. …

The white paper was produced as a collaboration by technical staff at the Department of Energy, the National Science Foundation, the Department of Defense, the National Institute of Standards and Technology, and the Intelligence Community. …

The white paper titled “A Federal Vision for Future Computing: A Nanotechnology-Inspired Grand Challenge” is 15 pp. and it offers tidbits such as this (Note: Footnotes not included),

A new materials base may be needed for future electronic hardware. While most of today’s electronics use silicon, this approach is unsustainable if billions of disposable and short-lived sensor nodes are needed for the coming Internet-of-Things (IoT). To what extent can the materials base for the implementation of future information technology (IT) components and systems support sustainability through recycling and bio-degradability? More sustainable materials, such as compostable or biodegradable systems (polymers, paper, etc.) that can be recycled or reused,  may play an important role. The potential role for such alternative materials in the fabrication of integrated systems needs to be explored as well. [p. 5]

The basic architecture of computers today is essentially the same as those built in the 1940s—the von Neumann architecture—with separate compute, high-speed memory, and high-density storage components that are electronically interconnected. However, it is well known that continued performance increases using this architecture are not feasible in the long term, with power density constraints being one of the fundamental roadblocks.7 Further advances in the current approach using multiple cores, chip multiprocessors, and associated architectures are plagued by challenges in software and programming models. Thus,  research and development is required in radically new and different computing architectures involving processors, memory, input-output devices, and how they behave and are interconnected. [p. 7]

Neuroscience research suggests that the brain is a complex, high-performance computing system with low energy consumption and incredible parallelism. A highly plastic and flexible organ, the human brain is able to grow new neurons, synapses, and connections to cope with an ever-changing environment. Energy efficiency, growth, and flexibility occur at all scales, from molecular to cellular, and allow the brain, from early to late stage, to never stop learning and to act with proactive intelligence in both familiar and novel situations. Understanding how these mechanisms work and cooperate within and across scales has the potential to offer tremendous technical insights and novel engineering frameworks for materials, devices, and systems seeking to perform efficient and autonomous computing. This research focus area is the most synergistic with the national BRAIN Initiative. However, unlike the BRAIN Initiative, where the goal is to map the network connectivity of the brain, the objective here is to understand the nature, methods, and mechanisms for computation,  and how the brain performs some of its tasks. Even within this broad paradigm,  one can loosely distinguish between neuromorphic computing and artificial neural network (ANN) approaches. The goal of neuromorphic computing is oriented towards a hardware approach to reverse engineering the computational architecture of the brain. On the other hand, ANNs include algorithmic approaches arising from machinelearning,  which in turn could leverage advancements and understanding in neuroscience as well as novel cognitive, mathematical, and statistical techniques. Indeed, the ultimate intelligent systems may as well be the result of merging existing ANN (e.g., deep learning) and bio-inspired techniques. [p. 8]

As government documents go, this is quite readable.

For anyone interested in learning more about the future federal plans for computing in the US, there is a July 29, 2016 posting on the White House blog celebrating the first year of the US National Strategic Computing Initiative Strategic Plan (29 pp. PDF; awkward but that is the title).

Memory material with functions resembling synapses and neurons in the brain

This work comes from the University of Twente’s MESA+ Institute for Nanotechnology according to a July 8, 2016 news item on ScienceDaily,

Our brain does not work like a typical computer memory storing just ones and zeroes: thanks to a much larger variation in memory states, it can calculate faster consuming less energy. Scientists of the MESA+ Institute for Nanotechnology of the University of Twente (The Netherlands) now developed a ferro-electric material with a memory function resembling synapses and neurons in the brain, resulting in a multistate memory. …

A July 8, 2016 University of Twente press release, which originated the news item, provides more technical detail,

The material that could be the basic building block for ‘brain-inspired computing’ is lead-zirconium-titanate (PZT): a sandwich of materials with several attractive properties. One of them is that it is ferro-electric: you can switch it to a desired state, this state remains stable after the electric field is gone. This is called polarization: it leads to a fast memory function that is non-volatile. Combined with processor chips, a computer could be designed that starts much faster, for example. The UT scientists now added a thin layer of zinc oxide to the PZT, 25 nanometer thickness. They discovered that switching from one state to another not only happens from ‘zero’ to ‘one’ vice versa. It is possible to control smaller areas within the crystal: will they be polarized (‘flip’) or not?

In a PZT layer without zinc oxide (ZnO) there are basically two memorystates. Adding a nano layer of ZnO, every state in between is possible as well.

Multistate

By using variable writing times in those smaller areas, the result is that many states can be stored anywhere between zero and one. This resembles the way synapses and neurons ‘weigh’ signals in our brain. Multistate memories, coupled to transistors, could drastically improve the speed of pattern recognition, for example: our brain performs this kind of tasks consuming only a fraction of the energy a computer system needs. Looking at the graphs, the writing times seem quite long compared to nowaday’s processor speeds, but it is possible to create many memories in parallel. The function of the brain has already been mimicked in software like neurale networks, but in that case conventional digital hardware is still a limitation. The new material is a first step towards electronic hardware with a brain-like memory. Finding solutions for combining PZT with semiconductors, or even developing new kinds of semiconductors for this, is one of the next steps.

Here’s a link to and a citation for the paper,

Multistability in Bistable Ferroelectric Materials toward Adaptive Applications by Anirban Ghosh, Gertjan Koster, and Guus Rijnders. Advanced Functional Materials DOI: 10.1002/adfm.201601353 Version of Record online: 4 JUL 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

3D brain-on-a-chip from the University of Twente

Dutch researchers have developed a 3D brain-on-a-chip according to a June 23, 2016 news item on Nanowerk,

To study brain cell’s operation and test the effect of medication on individual cells, the conventional Petri dish with flat electrodes is not sufficient. For truly realistic studies, cells have to flourish within three-dimensional surroundings.

Bart Schurink, researcher at University of Twente’s MESA+ Institute for Nanotechnology, has developed a sieve with 900 openings, each of which has the shape of an inverted pyramid. On top of this array of pyramids, a micro-reactor takes care of cell growth. Schurink defends his PhD thesis June 23 [2016].

A June 23, 2016 University of Twente press release, which originated the news item, provides more detail,

A brain-on-a-chip demands more than a series of electrodes in 2D, on which brain cells can be cultured. To mimic the brain in a realistic way, you need facilities for fluid flow, and the cells need some freedom for themselves even when they are kept at predefined spaces. Schurink therefore developed a micro sieve structure with hundreds of openings on a 2 by 2 mm surface. Each of these holes has the shape of  an inverted pyramid. Each pyramid, in turn, is equipped with an electrode, for measuring electrical signals or sending stimuli to the network. At the same time, liquids can flow through tiny holes, needed to capture the cells and for sending nutrients or medication to a single cell.

NEURONAL NETWORK

After neurons have been placed inside all the pyramids, they will start to form a network. This is not just a 2D network between the holes: by placing a micro reactor on top of the sieve, a neuron network can develop in the vertical direction as well. Growth and electrical activity can be monitored subsequently: each individual cell can be identified by the pyramid it is in. Manufacturing this system, demands a lot of both the production facilities at UT’s NanoLab and of creative solutions the designers come up with. For example, finding the proper way of guaranteeing  the same dimensions for every hole, is quite challenging.

Schurink’s new µSEA (micro sieve electrode array) has been tested with living cells, from the brains of laboratory rats. Both the positioning of the cells and neuronal network growth have been tested. The result of this PhD research is a fully new research platform for performing research on the brain, diseases and effects of medication.

Schurink (1982) has conducted his research within the group Meso Scale Chemical Systems, of Prof Han Gardeniers. The group is part of the MESA+ Institute for Nanotechnology of the University of Twente. Schurink’s thesis is titled ‘Microfabrication and microfluidics for 3D brain-on-chip’ …

I have written about one other piece about a ‘3D’ organ-on-a-chip project in China (my Jan. 29, 2016 posting).