Signal molecules leave one neuron from that bulby thing, float across a gap, and are picked up by receptors on the other neuron. In this way, information is transmitted from cell to cell … and thinking is possible.
But thanks to a bunch of German scientists - we now have a much more complete and accurate picture. They’ve created the first scientifically accurate 3D model of a synaptic bouton (that bulby bit) complete with every protein and cytoskeletal element.
This effort has been made possible only by a collaboration of specialists in electron microscopy, super-resolution light microscopy (STED), mass spectrometry, and quantitative biochemistry.
says the press release. The model reveals a whole world of neuroscience waiting to be explored. Exciting stuff!
Credit: Benjamin G. Wilhelm, Sunit Mandad, Sven Truckenbrodt, Katharina Kröhnert, Christina Schäfer, Burkhard Rammner, Seong Joo Koo, Gala A. Claßen, Michael Krauss, Volker Haucke, Henning Urlaub, Silvio O. Rizzoli
Neuroscientists have an extraordinary challenge to see how the brain works. It functions so quickly and is so densely populated with neuron networks and their supporting cells, technology is not yet advanced enough to allow us to see everything at once. But new methods and technologies are constantly evolving; here’s an image of a whole Zebrafish brain caught in the process sending messages. Every bright spot in the picture is an individual neuron filled with calcium – an ion that floods into the nerve cell when it sends a message. This method enables researchers to see how the whole brain works together and see how the activation of single neurons add together in the larger network. With methods like this it could be possible to map the function of every neuron network in the brain, helping to pinpoint the cause of disorders like epilepsy or schizophrenia.
This is a colourful slice through an autopsy sample – a brain taken from an 83 year-old woman. Red, green and blue fluorescent dyes highlight different chemical ‘messages’, called neuropeptides, being sent between brains cells (neurons). Two of these messages (kisspeptin, labelled in red and neurokinin, blue) often work together (shown where their overlapping dyes produce purples splodges) to trigger bursts of gonadotropin-releasing hormone, an important regulator of fertility and reproduction. But this elderly lady’s brain had also been sending a different chemical message (substance P, coloured green) at the same time – and often from the same neurons as kisspeptin (producing yellow splodges) or neurokinin (turquoise), or even in a triple-message combo (white). Neurons carrying substance P are more plentiful in the brains of elderly women than men, suggesting it could play a vital role in ‘rewiring’ hormone regulation in the female brain during the menopause.
Neurons are labeled in multiple colors with Brainbow fluorescence microscopy. Three fluorescent proteins (cyan, yellow and red) are randomly taken up by various neurons, offering a palette of dozens of colors to help scientists follow complex neural pathways. Shown here is a five-day-old zebra fish larva viewed from the dorsal side, captured using a 20X objective.
Image credit: Dr. Albert Pan, Harvard University, Cambridge, Mass., U.S.
Comb jellies are ancient marine predators whose comb-like cilia refract light as they swim. Biologists are intrigued by their highly unusual nervous systems.
When Leonid Moroz, a neuroscientist at the Whitney Laboratory for Marine Bioscience in St. Augustine, Fla., first began studying comb jellies, he was puzzled. He knew the primitive sea creatures had nerve cells — responsible, among other things, for orchestrating the darting of their tentacles and the beat of their iridescent cilia. But those neurons appeared to be invisible. The dyes that scientists typically use to stain and study those cells simply didn’t work. The comb jellies’ neural anatomy was like nothing else he had ever encountered.
After years of study, he thinks he knows why. According to traditional evolutionary biology, neurons evolved just once, hundreds of millions of years ago, likely after sea sponges branched off the evolutionary tree. But Moroz thinks it happened twice — once in ancestors of comb jellies, which split off at around the same time as sea sponges, and once in the animals that gave rise to jellyfish and all subsequent animals, including us. He cites as evidence the fact that comb jellies have a relatively alien neural system, employing different chemicals and architecture from our own. “When we look at the genome and other information, we see not only different grammar but a different alphabet,” Moroz said.
When Moroz proposed his theory, evolutionary biologists were skeptical. Neurons are the most complex cell type in existence, critics argued, capable of capturing information, making computations and executing decisions. Because they are so complicated, they are unlikely to have evolved twice.
But new support for Moroz’s idea comes from recent genetic work suggesting that comb jellies are ancient — the first group to branch off the animal family tree. If true, that would bolster the chance that they evolved neurons on their own.
The debate has generated intense interest among evolutionary biologists. Moroz’s work does not only call into question the origins of the brain and the evolutionary history of animals. It also challenges the deeply entrenched idea that evolution progresses steadily forward, building up complexity over time.
The First Split
Somewhere in the neighborhood of 540 million years ago, the ocean was poised for an explosion of animal life. The common ancestor of all animals roamed the seas, ready to diversify into the rich panoply of fauna we see today.
Scientists have long assumed that sponges were the first to branch off the main trunk of the animal family tree. They’re one of the simplest classes of animals, lacking specialized structures, such as nerves or a digestive system. Most rely on the ambient flow of water to collect food and remove waste.
Later, as is generally believed, the rest of the animal lineage split into comb jellies, also known as ctenophores (pronounced TEN-oh-fours); cnidarians (jellyfish, corals and anemones); very simple multicellular animals called placozoa; and eventually bilaterians, the branch that led to insects, humans and everything in between.
But sorting out the exact order in which the early animal branches split has been a notoriously thorny problem. We have little sense of what animals looked like so many millions of years ago because their soft bodies left little tangible evidence in rocks. “The fossil record is spotty,” said Linda Holland, an evolutionary biologist at the Scripps Institution of Oceanography at the University of California, San Diego.
Researchers Thursday unveiled a powerful new postage-stamp size chip delivering supercomputer performance using a process that mimics the human brain.
The so-called “neurosynaptic” chip is a breakthrough that opens a wide new range of computing possibilities from self-driving cars to artificial intelligence systems that can installed on a smartphone, the scientists say.
The researchers from IBM, Cornell Tech and collaborators from around the world said they took an entirely new approach in design compared with previous computer architecture, moving toward a system called “cognitive computing.”
“We have taken inspiration from the cerebral cortex to design this chip,” said IBM chief scientist for brain-inspired computing, Dharmendra Modha, referring to the command center of the brain.
I enjoy Asian art. I particularly love minimalist scroll and screen painting from the Edo period in Japan. I am also a fan of neuroscience. Therefore, it was a fine day when two of my passions came together upon the realization that the elegant forms of neurons (the cells that comprise your brain) can be painted expressively in the Asian sumi-e style. Neurons may be tiny in scale, but they posess the same beauty seen in traditional forms of the medium (trees, flowers, and animals).
Here are some of the winners from Science’s annual Visualization Challenge - you can see lots more here.
Top image: “Invisible Coral Flows” by Vicente I. Fernandez, Orr H. Shapiro, Melissa S. Garren, Assaf Vardi, Roman Stocker (MIT). The cilia of coral polyps stir up the water, helping them get food and dispose of nutrients.
Bottom image: “Cortex in Metallic Pastels” by Greg Dunn, Brian Edwards (Greg Dunn Design), Marty Saggese (SfN), Tracy Bale (UPenn), and Rick Huganir (Johns Hopkins University). Dunn used gold leaf, aluminum and acrylic dye to show the layered cellular structure of the cerebral cortex. Dunn: “The neurons are painted by a technique wherein pigments are blown across the canvas using jets of air, a technique that closely emulates the spontaneous, random branching patterns of actual neurons.”
A team of researchers at the IRCM led by Frédéric Charron, PhD, in collaboration with bioengineers at McGill University, uncovered
a new kind of synergy in the development of the nervous system, which
explains an important mechanism required for neural circuits to form
properly. Their breakthrough, published today in the scientific journal PLoS Biology,
could eventually help develop tools to repair nerve cells following
injuries to the nervous system (such as the brain and spinal cord).
Researchers in Dr. Charron’s laboratory
study neurons, the nerve cells that make up the central nervous system,
as well as their long extensions known as axons. During development,
axons must follow specific paths in the nervous system in order to
properly form neural circuits and allow neurons to communicate with one
another. IRCM researchers are studying a process called axon guidance to
better understand how axons manage to follow the correct paths.
“To reach their target, growing axons rely
on molecules known as guidance cues, which instruct them on which
direction to take by repelling or attracting them to their destination,”
explains Dr. Charron, Director of the Molecular Biology of Neural
Development research unit at the IRCM.
Over the past few decades, the scientific
community has struggled to understand why more than one guidance cue
would be necessary for axons to reach the proper target. In this paper,
IRCM scientists uncovered how axons use information from multiple
guidance cues to make their pathfinding decisions. To do so, they
studied the relative change in concentration of guidance cues in the
neuron’s environment, which is referred to as the steepness of the
“We found that the steepness of the gradient
is a critical factor for axon guidance; the steeper the gradient, the
better the axons respond to guidance cues,” says Tyler F.W. Sloan,
PhD student in Dr. Charron’s laboratory and first author of the study.
“In addition, we showed that the gradient of one guidance cue may not be
steep enough to orient axons. In those instances, we revealed that a
combination of guidance cues can behave in synergy with one another to
help the axon interpret the gradient’s direction.”
In collaboration with the Program in
Neuroengineering at McGill University, Dr. Charron’s team developed an
innovative technique to recreate the concentration gradients of guidance
cues in vitro, that is to say they can study the developing axons outside their biological context.
“This new method provides us with several
benefits when compared to previous techniques, and allows us to simulate
more realistic conditions encountered in developing embryos, conduct
longer-term experiments to observe the entire process of axon guidance,
and obtain extremely useful quantitative data,” adds Sloan. “It combines
knowledge from the field of microfluidics, which uses fluids at a
microscopic scale to miniaturize biological experiments, with the
cellular, biological and molecular studies we conduct in laboratories.”
“This is true multidisciplinary work, and an
excellent example of what the Program in Neuroengineering aims to
accomplish in situations where neurobiologists like myself have a
specific question they want to address, but the current tools aren’t
adapted to answer their question,” mentions Dr. Charron. “Thus, thanks
to this unique program, we teamed up with McGill’s bioengineers and
microfluidic and mathematical modelling experts to create the device
required for our study.”
“This scientific breakthrough could bring us
closer to repairing damaged nerve cells following injuries to the
central nervous system,” states Dr. Charron. “A better understanding of
the mechanisms involved in axon guidance will offer new possibilities
for developing techniques to treat lesions resulting from spinal cord
injuries, and possibly even neurodegenerative diseases.”
Injuries to the central nervous system
affect thousands of Canadians every year and can lead to lifelong
disabilities. Most often caused by an accident, stroke or disease, these
injuries are currently very difficult to repair. Research is therefore
required for the development of new tools to repair damage to the
central nervous system.
Researchers Show How Lost Sleep Leads to Lost Neurons
First report in preclincal study showing extended wakefulness can result in neuronal injury.
Most people appreciate that not getting enough sleep impairs cognitive performance. For the chronically sleep-deprived such as shift workers, students, or truckers, a common strategy is simply to catch up on missed slumber on the weekends. According to common wisdom, catch up sleep repays one’s “sleep debt,” with no lasting effects. But a new Penn Medicine study shows disturbing evidence that chronic sleep loss may be more serious than previously thought and may even lead to irreversible physical damage to and loss of brain cells. The research is published today in the Journal of Neuroscience.
A scanning electron micrograph (SEM) of a freeze-fractured cross section through a nerve bundle.
Axons (brown) of nerve cells are surrounded by insulating cells called the myeline sheet (purple). These allow for more efficient conduction of nerve impulses along these huge cells. The sciatic nerve in mammals goes from the base of the spine, to the bottom of your feet. These cells can reach up to more than a meter depending on how tall you are. The perinuerium is the connective tissue (blue) that surrounds the structure.
Dendrites, the branch-like projections of neurons, were once thought to be passive wiring in the brain. But now researchers at the University of North Carolina at Chapel Hill have shown that these dendrites do more than relay information from one neuron to the next. They actively process information, multiplying the brain’s computing power.
“Suddenly, it’s as if the processing power of the brain is much greater than we had originally thought,” said Spencer Smith, PhD, an assistant professor in the UNC School of Medicine.
His team’s findings, published October 27 in the journal Nature, could change the way scientists think about long-standing scientific models of how neural circuitry functions in the brain, while also helping researchers better understand neurological disorders.
“Imagine you’re reverse engineering a piece of alien technology, and what you thought was simple wiring turns out to be transistors that compute information,” Smith said. “That’s what this finding is like. The implications are exciting to think about.”
Axons are where neurons conventionally generate electrical spikes, but many of the same molecules that support axonal spikes are also present in the dendrites. Previous research using dissected brain tissue had demonstrated that dendrites can use those molecules to generate electrical spikes themselves, but it was unclear whether normal brain activity involved those dendritic spikes. For example, could dendritic spikes be involved in how we see?
The answer, Smith’s team found, is yes. Dendrites effectively act as mini-neural computers, actively processing neuronal input signals themselves.
Directly demonstrating this required a series of intricate experiments that took years and spanned two continents, beginning in senior author Michael Hausser’s lab at University College London, and being completed after Smith and Ikuko Smith, PhD, DVM, set up their own lab at the University of North Carolina. They used patch-clamp electrophysiology to attach a microscopic glass pipette electrode, filled with a physiological solution, to a neuronal dendrite in the brain of a mouse. The idea was to directly “listen” in on the electrical signaling process.
“Attaching the pipette to a dendrite is tremendously technically challenging,” Smith said. “You can’t approach the dendrite from any direction. And you can’t see the dendrite. So you have to do this blind. It’s like fishing if all you can see is the electrical trace of a fish.” And you can’t use bait. “You just go for it and see if you can hit a dendrite,” he said. “Most of the time you can’t.”
But Smith built his own two-photon microscope system to make things easier.
Once the pipette was attached to a dendrite, Smith’s team took electrical recordings from individual dendrites within the brains of anesthetized and awake mice. As the mice viewed visual stimuli on a computer screen, the researchers saw an unusual pattern of electrical signals – bursts of spikes – in the dendrite.
Smith’s team then found that the dendritic spikes occurred selectively, depending on the visual stimulus, indicating that the dendrites processed information about what the animal was seeing.
To provide visual evidence of their finding, Smith’s team filled neurons with calcium dye, which provided an optical readout of spiking. This revealed that dendrites fired spikes while other parts of the neuron did not, meaning that the spikes were the result of local processing within the dendrites.
Study co-author Tiago Branco, PhD, created a biophysical, mathematical model of neurons and found that known mechanisms could support the dendritic spiking recorded electrically, further validating the interpretation of the data.
“All the data pointed to the same conclusion,” Smith said. “The dendrites are not passive integrators of sensory-driven input; they seem to be a computational unit as well.”
His team plans to explore what this newly discovered dendritic role may play in brain circuitry and particularly in conditions like Timothy syndrome, in which the integration of dendritic signals may go awry.
Image1: A network of pyramidal cells in the cerebral cortex. These neurons have been simulated using a computer program which captures the beautiful dendritic architecture of real pyramidal cells. These dendrites have now been shown to carry out sophisticated computations on their inputs. Credit: UCL.
Image2: This is a dendrite, the branch-like structure of a single neuron in the brain. The bright object from the top is a pipette attached to a dendrite in the brain of a mouse. The pipette allows researchers to measure electrical activity, such as a dendritic spike, the bright spot in the middle of the image. Credit: Spencer Smith