Posts tagged neuron
Articles and news from the latest research reports.
Study reveals how the brain categorizes thousands of objects and actions
Humans perceive numerous categories of objects and actions, but where are these categories represented spatially in the brain?
Researchers reporting in the December 20 issue of the Cell Press journal Neuron present their study that undertook the remarkable task of determining how the brain maps over a thousand object and action categories when subjects watched natural movie clips. The results demonstrate that the brain efficiently represents the diversity of categories in a compact space. Instead of having a distinct brain area devoted to each category, as previous work had identified, for some but not all types of stimuli, the researchers uncovered that brain activity is organized by the relationship between categories.
"Humans can recognize thousands of categories. Given the limited size of the human brain, it seems unreasonable to expect that every category is represented in a distinct brain area," says first author Alex Huth, a graduate student working in Dr. Jack Gallant’s laboratory at the University of California, Berkeley. The authors proposed that perhaps a more efficient way for the brain to represent object and action categories would be to organize them into a continuous space that reflects the similarity between categories.
To test this hypothesis, they used blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) to measure human brain activity evoked by natural movies in five people. They then mapped out how 1,705 distinct object and action categories are represented across the surface of the cortex of the brain. Their results show that categories are organized as smooth gradients that cover much of the surface of the visual as well as nonvisual cortex, such that similar categories are located next to each other, and notably, this organization was shared across the individuals imaged.
"Discovering the feature space that the brain uses to represent information helps us to recover functional maps across the cortical surface. The brain probably uses similar mechanisms to map other kinds of information across the cortical surface, so our approach should be widely applicable to other areas of cognitive neuroscience," says Dr. Gallant.
More than a century after it was first identified, Harvard scientists are shedding new light on a little-understood neural feedback mechanism that may play a key role in how the olfactory system works in the brain.
As described in a December 19 paper in Neuron by Venkatesh Murthy, Professor of Molecular and Cellular Biology, researchers have, for the first time, described how that feedback mechanism works by identifying where the signals go, and which type of neurons receive them. Three scientists from the Murthy lab were involved in the work: Foivos Markopoulos, Dan Rokni and David Gire.
"The image of the brain as a linear processor is a convenient one, but almost all brains, and certainly mammalian brains, do not rely on that kind of pure feed-forward system," Murthy explained. "On the contrary, it now appears that the higher regions of the brain which are responsible for interpreting olfactory information are communicating with lower parts of the brain on a near-constant basis."
Though researchers have known about the feedback system for decades, key questions about its precise workings, such as which neurons in the olfactory bulb receive the feedback signals, remained a mystery, partly because scientists simply didn’t have the technological tools needed to activate individual neurons and individual pathways.
"One of the challenges with this type of research is that these feedback neurons are not the only neurons that come back to the olfactory bulb," Murthy explained. "The challenge has always been that there’s no easy way to pick out just one type of neuron to activate."
To do it, Murthy and his team turned to a technique called optogenetics.
Using a virus that has been genetically-modified to produce a light-sensitive protein, Murthy and his team marked specific neurons, which become active when hit with laser light. Researchers were then able to trace the feedback mechanism from the brain’s processing centers back to the olfactory bulb.
Reaching that level of precision was critical, Murthy explained, because while olfactory bulb contains many “principal” neurons which are responsible for sending signals on to other parts of the brain, it is also packed with interneurons, which appear to play a role in formatting olfactory information as it comes into the brain.
(Image: BigStock)
Gut instincts: The secrets of your second brain
When it comes to your moods, decisions and behaviour, the brain in your head is not the only one doing the thinking
IT’S been a tough morning. You were late for work, missed a crucial meeting and now your boss is mad at you. Come lunchtime you walk straight past the salad bar and head for the stodge. You can’t help yourself - at times of stress the brain encourages us to seek out comfort foods. That much is well known. What you probably don’t know, though, is that the real culprit may not be the brain in your skull but your other brain.
Yes, that’s right, your other brain. Your body contains a separate nervous system that is so complex it has been dubbed the second brain. It comprises an estimated 500 million neurons - about five times as many as in the brain of a rat - and is around 9 metres long, stretching from your oesophagus to your anus. It is this brain that could be responsible for your craving under stress for crisps, chocolate and cookies.
Embedded in the wall of the gut, the enteric nervous system (ENS) has long been known to control digestion. Now it seems it also plays an important role in our physical and mental well-being. It can work both independently of and in conjunction with the brain in your head and, although you are not conscious of your gut “thinking”, the ENS helps you sense environmental threats, and then influences your response. “A lot of the information that the gut sends to the brain affects well-being, and doesn’t even come to consciousness,” says Michael Gershon at Columbia-Presbyterian Medical Center, New York.
Neurons die in Alzheimer’s because of faulty cell cycle control before plaques and tangles appear
The two infamous proteins, amyloid-beta (Aβ) and tau, that characterize advanced Alzheimer’s disease (AD), start healthy neurons on the road to cell death long before the appearance of the deadly plaques and tangles by working together to reactivate the supposedly blocked cell cycle in brain cells, according to research presented on Dec. 17 at the American Society for Cell Biology’s Annual Meeting in San Francisco.
Working in a mouse model of AD, George Bloom, PhD, of the University of Virginia (UVA) reports that neurons in AD start dying because they break the first law of human neuronal safety ⎯ stay out of the cell cycle.
Most normal adult neurons are permanently postmitotic; that is, they have finished dividing and are locked out of the cell cycle. In contrast, AD neurons frequently re-enter the cell cycle but fail to complete mitosis, and ultimately die. By considering this novel perspective on AD as a problem of the cell cycle, Dr. Bloom and colleagues at UVA and at the University of Alabama, Birmingham, have discovered what they call an “ironic pathway” to neuronal cell death. The process requires the coordinated action of both Aβ and tau, which are the building blocks of plaques and tangles, respectively. Dr. Bloom’s results show just how toxic the two proteins can be even when free in solution and not aggregated into plaques and tangles.
Using mouse neurons grown in culture, the UVA researchers found that Aβ oligomers, which are small aggregates of just a few Aβ molecules each, induce the neurons to re-enter the cell cycle. Interestingly, the neurons must make and accumulate tau in order for this cell cycle re-entry to occur. The mechanism for this misplaced re-entry into the cell cycle requires that Aβ oligomers activate multiple protein kinase enzymes, each of which must then attach a phosphate to a specific site on the tau protein.
Following up on the cell culture results, Dr. Bloom and colleagues confirmed that Aβ-induced, tau-dependent cell cycle re-entry occurs in the brains of mice that were genetically engineered to mimic brains with human AD. The mouse brains were found to accumulate massive numbers of neurons that had transitioned from a permanent cell cycle stop, known as G0 (G zero), to G1, the first stage of the cell cycle, by the time they were 6 months old. Remarkably, otherwise identical mice that lacked functional tau genes showed no sign of cell cycle re-entry, confirming the cell culture results.
Neuronal cell cycle re-entry, a key step in the development of AD, can therefore be caused by signaling from Aβ through tau. Thus, Aβ and tau co-conspire to trigger seminal events in AD pathogenesis independently of their incorporation into plaques and tangles. Most important, Dr. Bloom believes that the activated protein kinases and phosphorylated forms of tau identified in this study represent potential targets for early diagnosis and treatment of AD.
(Source: eurekalert.org)
The end of a dogma: Bipolar cells generate action potentials
To make information transmission to the brain reliable, the retina first has to “digitize” the image. Until now, it was widely believed that this step takes place in the retinal ganglion cells, the output neurons of the retina. Scientists in the lab of Thomas Euler at the University of Tübingen, the Werner Reichardt Centre for Integrative Neuroscience and the Bernstein Center Tübingen were now able to show that already bipolar cells can generate “digital” signals. At least three types of mouse BC showed clear evidence of fast and stereotypic action potentials, so called “spikes”. These results show that the retina is by no means as well understood as is commonly believed.
The retina in our eyes is not just a sheet of light sensors that – like a camera chip – faithfully transmits patterns of light to the brain. Rather, it performs complex computations, extracting several features from the visual stimuli, e.g., whether the light intensity at a certain place increases or decreases, in which direction a light source moves or whether there is an edge in the image. To transmit this information reliably across the optic nerve - acting as a kind of a cable - to the brain, the retina reformats it into a succession of stereotypic action potentials – it “digitizes” it. Classical textbook knowledge holds that this digital code – similar to the one employed by computers – is applied only in the retina’s ganglion cells, which send the information to the brain. Almost all other cells in the retina were believed to employ graded, analogue signals. But the Tübingen scientists could now show that, in mammals, already the bipolar cells, which are situated right after the photoreceptors within the retinal network, are able to work in a “digital mode” as well.
Using a new experimental technique, Tom Baden and colleagues recorded signals in the synaptic terminals of bipolar cells in the mouse retina. Based on the responses of these cells to simple light stimuli, they were able to separate the neurons into eight different response types. These types closely resembled those expected from physiological and anatomical studies. But surprisingly, the responses of the fastest cell types looked quite different than expected: they were fast, stereotypic and occurred in an all-or-nothing instead of a graded fashion. All these are typical features of action potentials. Such “digital” signals had occasionally been observed in bipolar cells before, but these were believed to be rare exceptional cases. Studies from the past two years on the fish retina had already cast doubt on the long-held belief that BCs do not spike. The new data from Tübingen clearly show that these “digital” signals are systematically generated in certain types of mammalian bipolar cells. Action potentials allow for much faster and temporally more precise signal transmission than graded potentials, thus offering advantages in certain situations. The results from Tübingen call a widely held dogma of neuroscience into question - and open up many new questions.
The nematode worm (scientific name C. elegans) is a simple-minded animal: it has exactly 302 neurons (compare that to a human’s roughly 100 billion). The pattern of connections between these neurons was painstakingly mapped out decades ago using electron microscopy, but it turns out that knowledge of the connections is not sufficient to understand (or even replicate) the information processor they represent. For example, some connections are inhibitory while others are excitatory, but this map doesn’t say which is which.
In order to learn how one neuron affects another, we need to see what happens when the first neuron is activated. NEMALOAD (“nematode upload”) is a project to integrate a number of recent technologies that should make this feasible, at least in C. elegans, and using this capability to replicate the information processing structure that governs the worm’s behavior in a digital model.
Researchers at Stanford University have successfully induced and relieved depression-like deficiencies in both pleasure and motivation in mice by controlling just a single area of the brain known as the ventral tegmental area. It is the first time that well-defined types of neurons within a specific brain region have been directly tied to the control of myriad symptoms of major depressive illness.
In the paper published in Nature on Dec. 12, Stanford bioengineer Karl Deisseroth, MD, PhD, and a team including postdoctoral scholars Kay Tye, PhD, and Melissa Warden, PhD, and research assistant Julie Mirzabekov have used a technique known as optogenetics to pinpoint a specific brain location that produces multiple depression-like symptoms. The region in question is the ventral tegmental area, or VTA, a source of dopamine and a central player in the brain’s internal motivation and reward systems.
“We have for the first time directly tied dopamine neurons in the VTA to controlling and relieving these very different and diverse symptoms,” said Deisseroth, the study’s senior author and a professor of bioengineering and of psychiatry and behavioral sciences. “While depression is a complex disease with still many unknowns, this knowledge may help launch new kinds of investigation into the pathways of depression in the brain, and develop concepts to help people suffering from depression.”
Deisseroth’s team was able to both induce and relieve multiple depression-like symptoms in laboratory mice by genetically modifying the dopamine neurons in the VTA to be sensitive to light. Using fiber optic cables inserted in rodents’ brains, they could then instantaneously produce and inhibit the depression-like symptoms by turning the light on and off. This research technique, developed by Deisseroth at Stanford in 2005, is known as optogenetics.
(Image Credit: iStockphoto.com)
Mayo Clinic Researchers Uncover Toxic Interaction in Neurons that Leads to Dementia and ALS
Researchers at Mayo Clinic in Florida have uncovered a toxic cellular process by which a protein that maintains the health of neurons becomes deficient and can lead to dementia. The findings shed new light on the link between culprits implicated in two devastating neurological diseases: frontotemporal dementia and amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease. The study is published Dec. 10 in the online issue of Proceedings of the National Academy of Sciences.
There is no cure for frontotemporal dementia, a disorder that affects personality, behavior and language and is second only to Alzheimer’s disease as the most common form of early-onset dementia. While much research is devoted to understanding the role of each defective protein in these diseases, the team at Mayo Clinic took a new approach to examine the interplay between TDP-43, a protein that regulates messenger ribonucleic acid (mRNA) — biological molecules that carry the information of genes and are used by cells to guide protein synthesis — and sortilin, which regulates the protein progranulin.
"We sought to investigate how TDP-43 regulates the levels of the protein progranulin, given that extreme progranulin levels at either end of the spectrum, too low or too high, can respectively lead to neurodegeneration or cancer," says the study’s lead investigator, Mercedes Prudencio, Ph.D., a neuroscientist at the Mayo Clinic campus in Florida.
The neuroscientists found that a lack of the protein TDP-43, long implicated in frontotemporal dementia and amyotrophic lateral sclerosis, leads to elevated levels of defective sortilin mRNA. The research team is the first to identify significantly elevated levels of the defective sortilin mRNA in autopsied human brain tissue of frontotemporal dementia/TDP cases, the most common subtype of the disease.
(Image: Wikimedia Commons)
Genetic cause discovered for rare disorder of motor neurones
Scientists have identified an underlying genetic cause for a rare disorder of motor neurones, and believe this may help find causes of other related diseases.
Disorders of motor neurones are a group of progressive neuromuscular disorders that damage the nervous system, causing muscle weakness and wasting. These diseases affect many thousands of people in the UK. A number are inherited but the causes of the majority remain unknown, and there are no cures.
The new study has discovered a gene mutation that causes a rare disorder of motor neurones called distal hereditary motor neuropathy (dHMN). The researchers say their findings raise a possibility that mutations of the same gene or genes with similar roles might underlie other disorders of motor neurones. This could open up the potential for new treatment options, not only for dHMN but also for the wider group of these disorders.
dHMN principally affects muscles of the hands and feet, and sometimes causes a hoarse voice. Symptoms usually begin during adolescence although this can vary from infancy to the mid-thirties.
The study to investigate possible genetic causes of dHMN was led by Professor Andrew Crosby and Dr Meriel McEntagart at St George’s, University of London. It has been published in the American Journal of Human Genetics.
Do brain cells need to be connected to have meaning?
The classic theory of the brain is one of connections, in which the brain consists of a network of neurons that interact with each other to allow us to think, see, interpret, and understand the world around us. In this model, called distributed representation, an individual neuron by itself has no inherent meaning, but only contributes to a pattern of neuronal activity that has meaning. For example, a certain pattern of many neurons fires when you think “dog” and another pattern for “cat.”
"The belief in distributed representation theory is that a concept or object is not represented by a single neuron in the brain but by a pattern of activations over a number of neurons," explains Asim Roy, a professor of information systems at Arizona State University, to Medical Xpress . "Thus there is no single neuron in the brain representing a cat or a dog. Proponents of this theory claim that a cat or a dog is represented by its microfeatures such as legs, ears, body, tail, and so on. However, they think that neurons have absolutely no meaning on a stand-alone basis. Therefore, they go further and claim that these microfeatures are at the subsymbolic level, which means that meaning arises only when you consider the pattern of activations as a whole. Therefore, there are no neurons representing legs, ears, body, tail, etc. The representation is at a much lower level."
Roy is among a number of scientists working in the fields of neuroscience and artificial intelligence (AI) who suspect that the brain may not be as connected as distributed representation suggests. The basis of their alternative model, called localist representation, is that a single neuron can represent a dog, a cat, or any other object or concept. These neurons can be considered symbols since they have meaning on a stand-alone basis. However, as Roy explains, this doesn’t necessarily mean only one neuron represents a dog; such “concept cells” are high-level neurons, which fire in response to the firing of an assortment of low-level neurons that represent the legs, ears, body, tail, etc.
"In localist representation, there could be separate neurons for a dog and a cat, and also neurons for legs, ears, body, tail, etc.," he said. "It’s very similar to the model in my paper for word recognition, which is an old model from James McClelland [Chair of the Psychology Department at Stanford University] and [the late pioneering neuroscientist] David Rumelhart. You have low-level neurons that detect letters of the alphabet and then high-level neurons for individual words. So letter neurons and word neurons, they both exist."
The origins of this dispute between localist and distributed representation goes back to the early ’80s, to a dispute between the symbol processing hypothesis of artificial intelligence (AI) and the subsymbolic paradigm of connectionists. In the past 30 years, the debate has only intensified.