Posts tagged neurons
Articles and news from the latest research reports.
Activity in dendrites is critical in memory formation
Why do we remember some things and not others? In a unique imaging study, two Northwestern University researchers have discovered how neurons in the brain might allow some experiences to be remembered while others are forgotten. It turns out, if you want to remember something about your environment, you better involve your dendrites.
Using a high-resolution, one-of-a-kind microscope, Daniel A. Dombeck and Mark E. J. Sheffield peered into the brain of a living animal and saw exactly what was happening in individual neurons called place cells as the animal navigated a virtual reality maze.
The scientists found that, contrary to current thought, the activity of a neuron’s cell body and its dendrites can be different. They observed that when cell bodies were activated but the dendrites were not activated during an animal’s experience, a lasting memory of that experience was not formed by the neurons. This suggests that the cell body seems to represent ongoing experience, while dendrites, the treelike branches of a neuron, help to store that experience as a memory.
"There are a lot of theories on memory but very little data as to how individual neurons actually store information in a behaving animal," said Dombeck, assistant professor of neurobiology in the Weinberg College of Arts and Sciences and the study’s senior author. "Now we have uncovered signals in dendrites that we think are very important for learning and memory. Our findings could explain why some experiences are remembered and others are forgotten."
In the brain’s hippocampus, there are hundreds of thousands of place cells — neurons essential to the brain’s GPS system. Dombeck and Sheffield are the first to image the activity of individual dendrites in place cells.
Their findings contribute to our understanding of how the brain represents the world around it and also point to dendrites as a new potential target for therapeutics to combat memory deficits and debilitating diseases, such as Alzheimer’s disease (AD). Disruption to the brain’s GPS system is one of the first symptoms of AD, with many patients unable to find their way home. Understanding how place cells and their dendrites store these types of memories could help us find new ways to treat the disease.
The Northwestern study will be published Oct. 26 by the journal Nature.
Neuroscientist John O’Keefe discovered place cells in 1971 (and received this year’s Nobel Prize in physiology and medicine), but it is only in the last few years that scientists, such as Dombeck and Sheffield, have been able to image these neurons that represent a map of where we are in our environment.
In their study, Dombeck and Sheffield found dendrite signals that could explain how an animal can experience something without storing the experience as a memory.
They saw that dendrites are not always activated when the cell body is activated in a neuron. Signals produced in the dendrites (used to store information) and signals within the neuron cell body (used to compute and transmit information) can be either highly synchronized or desynchronized depending on how well the neurons remember different features of the maze.
Scientists have long believed that the neuronal tasks of computing and storing information are connected — when neurons compute information, they are also storing it, and vice versa. The Northwestern study provides evidence against this classic view of neuronal function.
"We experience events all the time, which must be represented in the brain by the activity of neurons, but not all these events can be recalled later," said Mark E. J. Sheffield, a postdoctoral fellow in Dombeck’s lab and first author of the study.
"A daily commute to work, for example, requires the activity of millions of neurons, but you would be hard pressed to remember what was happening halfway through your commute last Tuesday," Sheffield said. "How is it then that the neurons could be activated during the commute without storing that information in the brain? Now we may have an explanation for how this occurs."
Dombeck and Sheffield built their own laser scanning microscope that can image neurons on multiple planes. They then studied individual animals navigating (on a trackball) a virtual reality maze constructed using the video game Quake II.
Each lit-up structure seen in the images they took indicate a neuron firing action potentials. The activity of these neurons represents an animal’s experience of where it is in the environment, the researchers said. Whether the neurons store this experience or not appears to depend on the activity of the neurons’ dendrites.
(Figure 1: A magnified image of a mouse brain showing memory cells (red) that can be turned ‘on’ and ‘off’ using light delivered by a fiber optic cable (black). Credit: © Susumu Tonegawa)
Memories get the emotional switch
Memories of experiences are encoded in the brain along with contextual and emotional information such as where the experience took place and whether it was positive or negative. This allows for the formation of memory associations that might assist in survival. Just how this positive and negative encoding occurs, however, has remained unclear.
Susumu Tonegawa and colleagues from the RIKEN–MIT Center for Neural Circuit Genetics have now discovered that neurons in the hippocampus region of the brain can be artificially switched to encode memories as either positive or negative regardless of the original experience.
Tonegawa’s research team used genetic techniques to mark neurons in the dorsal dentate gyrus region of the hippocampus and the basolateral complex of the amygdala (BLA) in male mice. Memories are encoded in both these regions as specific groups of activated cells called ‘engrams’, but each region encodes the memory in slightly different ways: the BLA encodes positive and negative memory ‘valence’, while the dorsal dentate gyrus encodes contextual information such as emotion.
The genetic labeling, which involved using a light-sensitive ion channel called channelrhodopsin, was activated by the formation of either a positive memory, in this case exposure to females, or a negative memory associated with a foot shock. The cells that expressed this channel could be subsequently activated by exposure to light (Fig. 1); doing so induced aversive responses in mice that had experienced foot shocks, and appetitive responses in those that had experienced female interactions.
The researchers then used light to activate the hippocampal or BLA neurons that had been labeled during the formation of a positive memory while exposing the mice to foot shocks. The next time the animals were tested, light activation of those hippocampal neurons that had initially induced appetitive responses instead led the mice to exhibit aversive responses. However, BLA neurons could not be switched in this way, indicating that only neurons in the hippocampus have plasticity in their encoding of positive or negative memories.
The valence of hippocampal neurons, the researchers found, could be switched from both good to bad and bad to good using this technique, with the switch attributed to a change in the strength of connections between the hippocampal and BLA neurons of each engram.
The findings provide new insight into how memories can be altered after they are formed. The possibility of inducing similar changes to memory valence in humans could also offer hope of a treatment for those suffering from conditions such as post-traumatic stress disorder.
Are Male Brains Wired to Ignore Food for Sex?
Choosing between two good things can be tough. When animals must decide between feeding and mating, it can get even trickier. In a discovery that might ring true even for some humans, researchers have shown that male brains – at least in nematodes – will suppress the ability to locate food in order to instead focus on finding a mate.
(Image caption: C. elegans male (top) and hermaphrodite (bottom))
The results, which appear today in the journal Current Biology, may point to how subtle changes in the brain’s circuitry dictate differences in behavior between males and females.
“While we know that human behavior is influenced by numerous factors, including cultural and social norms, these findings point to basic biological mechanisms that may not only help explain some differences in behavior between males and females, but why different sexes may be more susceptible to certain neurological disorders,” said Douglas Portman, Ph.D., an associate professor in the Department of Biomedical Genetics and Center for Neural Development and Disease at the University of Rochester and lead author of the study.
The findings were made in experiments involving C. elegans, a microscopic roundworm that has long been used by researchers to understand fundamental mechanisms in biology. Many of the discoveries made using C. elegans apply throughout the animal kingdom and this research has led to a broader understanding of human biology. In fact, three Nobel Prizes in medicine and chemistry have been awarded for discoveries involving C. elegans.
C. elegans is particularly useful in the study of the nervous system and scientists understand in great detail the development, function, and multiple connections of its entire neural network.
The study published today focuses on the activity of a single pair of neurons found in C. elegans – called AWA – that control smell. Smell, along with taste and touch, are critical sensory factors that dictate how C. elegans understands and navigates its environment, including finding food, avoiding danger, and locating a mate.
There are two sexes of C. elegans, males and hermaphrodites. Though the hermaphrodites are able to self-fertilize, they are also mating partners for males, and are considered to be modified females.
It has been previously observed that males and hermaphrodites act differently when exposed to food. If placed at a food source, the hermaphrodites tend to stay there. Males, however, will leave food source and “wander” – scientist believe they do this because they are in search of a mate.
The Rochester researchers discovered that the sensory mechanisms – called chemoreceptors – of the AWA neurons were regulated by the sexual identity of these cells, which, in turn, controls the expression of a receptor called ODR-10. These receptors bind to a chemical scent that is given off by food and other substances.
In hermaphrodites, more of the ODR-10 receptors are produced, making the worms more sensitive – and thereby attracted – to the presence of food. In males, fewer of these receptors are active, essentially suppressing their ability – and perhaps desire – to find food. However, when males were deprived of food, they produced dramatically higher levels of this receptor, allowing them to temporarily focus on finding food.
To confirm the role of these genetic differences between the sexes on behavior, the researchers designed a series of experiments in which they observed the activity of C. elegans when placed in a petri-dish and confronted with the option to either feed or go in search of a mate. The hermaphrodites were place in the center of the dish at a food source and, as expected, they stayed put.
The males were placed in their own individual food sources at the periphery of the dish. As a further obstacle between the males and their potential mates, an additional ring of food surrounded the hermaphrodites in the center of the dish. The males in the experiment consisted of two categories, one group with a normal genetic profile and another group that had been engineered by the researchers to overexpress the ODR-10 receptor, essentially making them more sensitive to the smell of food.
The researchers found that the normal worms left their food source and eventually made their way to the center of the dish where they mated with the hermaphrodites. The genetically engineered males were less successful at finding a mate, presumably because they were more interested in feeding. By examining the genetic profile of the resulting offspring, the scientists observed that the normal males out-produced the genetically engineered males by 10 to one.
In separate experiments, the researchers were also able to modify the behavior of the hermaphrodites by suppressing the ODR-10 receptors, causing them to act like males and abandon their food source.
“These findings show that by tuning the properties of a single cell, we can change behavior,” said Portman. “This adds to a growing body of evidence that sex-specific regulation of gene expression may play an important role in neural plasticity and, consequently, influence differences in behaviors – and in disease susceptibility – between the sexes.”
(Source: urmc.rochester.edu)
Neurons are electrically charged cells, located in the nervous system, that interpret and transmit information using electrical and chemical signals. Now, researchers at the University of Missouri have determined that individual neurons can react differently to electrical signals at the molecular level and in different ways—even among neurons of the same type. This variability may be important in discovering underlying problems associated with brain disorders and neural diseases such as epilepsy.
“Genetic mutations found in neurological disorders create imbalances in the inward and outward flow of electrical current through cells,” said David Schulz, associate professor in the Division of Biological Sciences in the College of Arts and Science and a researcher in the Interdisciplinary Neuroscience Program at MU. “Often, neurons react to electrical signals, or voltage, and compensate by altering their own electrical outputs. The variability in these imbalances, even among multiple cells of the same kind within the brain, is one of the major problems scientists face when trying to design therapeutics for disorders like epilepsy. Seizures in individuals can be caused by different imbalances—therefore getting to the root of how neurons act individually makes our studies important.”
Schulz and his team previously proved that two identical neurons can reach the same electrical activity in different ways. In his new study, Schulz hypothesized that neurons might use the cell’s genetic code, or its messenger RNA (mRNA), to “fine tune” the production of proteins, helping individual cells react accordingly.
Using clusters of neurons obtained from Jonah crabs, Schulz and his team experimentally altered electrical input and output in the neurons and measured the messenger RNA (mRNA) levels found within the cells. Invertebrates like crabs are useful in neuroscience research because their neurons are simple enough to observe and study, but advanced enough that they can be “scaled up” to apply to higher organisms, Schulz said.
They found that when normal patterns of stimulation were maintained, cells engaged the correct ratios of mRNA to produce the proteins needed to help keep electrical impulses in order; however, when normal patterns of activity were not maintained, this fundamentally changed the cells at the molecular level.
“We were the first to show that the correct ratios of mRNAs are actively maintained by the actual activity or voltage of the cell, and not chemical feedback,” Schulz said. “These results represent a novel aspect of regulation that might be useful for developing therapeutics for neuronal disorders later.”
Schulz’ study, “Activity-dependent feedback regulates correlated ion channel mRNA levels in single identified motor neurons,” was published in the August 18th edition of Current Biology.
(Image caption: Making “scents” of new cells in the brain’s odor-processing area. Adult-born cells travel through the thin rostral migratory stream before settling into the olfactory bulb, the large structure in the upper right of the image. Courtesy of the Belluscio Lab, NINDS)
Scientists sniff out unexpected role for stem cells in the brain
For decades, scientists thought that neurons in the brain were born only during the early development period and could not be replenished. More recently, however, they discovered cells with the ability to divide and turn into new neurons in specific brain regions. The function of these neuroprogenitor cells remains an intense area of research. Scientists at the National Institutes of Health (NIH) report that newly formed brain cells in the mouse olfactory system — the area that processes smells — play a critical role in maintaining proper connections. The results were published in the October 8 issue of the Journal of Neuroscience.
“This is a surprising new role for brain stem cells and changes the way we view them,” said Leonardo Belluscio, Ph.D., a scientist at NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and lead author of the study.
The olfactory bulb is located in the front of the brain and receives information directly from the nose about odors in the environment. Neurons in the olfactory bulb sort that information and relay the signals to the rest of the brain, at which point we become aware of the smells we are experiencing. Olfactory loss is often an early symptom in a variety of neurological disorders, including Alzheimer’s and Parkinson’s diseases.
In a process known as neurogenesis, adult-born neuroprogenitor cells are generated in the subventricular zone deep in the brain and migrate to the olfactory bulb where they assume their final positions. Once in place, they form connections with existing cells and are incorporated into the circuitry.
Dr. Belluscio, who studies the olfactory system, teamed up with Heather Cameron, Ph.D., a neurogenesis researcher at the NIH’s National Institute of Mental Health, to better understand how the continuous addition of new neurons influences the circuit organization of the olfactory bulb. Using two types of specially engineered mice, they were able to specifically target and eliminate the stem cells that give rise to these new neurons in adults, while leaving other olfactory bulb cells intact. This level of specificity had not been achieved previously.
In the first set of mouse experiments, Dr. Belluscio’s team first disrupted the organization of olfactory bulb circuits by temporarily plugging a nostril in the animals, to block olfactory sensory information from entering the brain. His lab previously showed that this form of sensory deprivation causes certain projections within the olfactory bulb to dramatically spread out and lose the precise pattern of connections that show under normal conditions. These studies also showed that this widespread disrupted circuitry could re-organize itself and restore its original precision once the sensory deprivation was reversed.
However, in the current study, Dr. Belluscio’s lab reveals that once the nose is unblocked, if new neurons are prevented from forming and entering the olfactory bulb, the circuits remain in disarray. “We found that without the introduction of the new neurons, the system could not recover from its disrupted state,” said Dr. Belluscio.
To further explore this idea, his team also eliminated the formation of adult-born neurons in mice that did not experience sensory deprivation. They found that the olfactory bulb organization began to break down, resembling the pattern seen in animals blocked from receiving sensory information from the nose. And they observed a relationship between the extent of stem cell loss and amount of circuitry disruption, indicating that a greater loss of stem cells led to a larger degree of disorganization in the olfactory bulb.
According to Dr. Belluscio, it is generally assumed that the circuits of the adult brain are quite stable and that introducing new neurons alters the existing circuitry, causing it to re-organize. “However, in this case, the circuitry appears to be inherently unstable requiring a constant supply of new neurons not only to recover its organization following disruption but also to maintain or stabilize its mature structure. It’s actually quite amazing that despite the continuous replacement of cells within this olfactory bulb circuit, under normal circumstances its organization does not change,” he said.
Dr. Belluscio and his colleagues speculate that new neurons in the olfactory bulb may be important to maintain or accommodate the activity-dependent changes in the system, which could help animals adapt to a constantly varying environment.
“It’s very exciting to find that new neurons affect the precise connections between neurons in the olfactory bulb. Because new neurons throughout the brain share many features, it seems likely that neurogenesis in other regions, such as the hippocampus, which is involved in memory, also produce similar changes in connectivity,” said Dr. Cameron.
The underlying basis of the connection between neurological disease and changes in the olfactory system is also unknown but may come from a better understanding of how the sense of smell works. “This is an exciting area of science,” said Dr. Belluscio, “I believe the olfactory system is very sensitive to changes in neural activity and given its connection to other brain regions, it could lend insight into the relationship between olfactory loss and many brain disorders.”
Hunger Games: How the brain ‘browns’ fat to aid weight loss
Researchers at Yale School of Medicine have uncovered a molecular process in the brain known to control eating that transforms white fat into brown fat. This process impacts how much energy we burn and how much weight we can lose. The results are published in the Oct. 9 issue of the journal Cell.
Obesity is a rising global epidemic. Excess fatty tissue is a major risk factor for type 2 diabetes, cardiovascular disease, hypertension, neurological disorders, and cancer. People become overweight and obese when energy intake exceeds energy expenditure, and excess calories are stored in the adipose tissues. The adipose organ is made up of both white and brown fat. While white fat primarily stores energy as triglycerides, brown fat dissipates chemical energy as heat. The more brown fat you have, the more weight you can lose.
It has previously been shown that energy-storing white fat has the capacity to transform into energy-burning “brown-like” fat. In this new study, researchers from the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, demonstrate that neurons controlling hunger and appetite in the brain control the “browning” of white fat.
Lead author Xiaoyong Yang, associate professor of comparative medicine and physiology at Yale School of Medicine, conducted the study with Tamas Horvath, professor and chair of comparative medicine, and professor of neurobiology and Obstetrics/gynecology at Yale School of Medicine, and their co-authors.
The team stimulated this browning process from the brain in mice and found that it protected the animals from becoming obese on a high-fat diet. The team then studied the molecular changes in hunger-promoting neurons in the hypothalamus and found that the attachment of a unique sugar called “O-GlcNAc” to potassium ion channels acts as a switch to control brain activity to burn fat.
“Our studies reveal white fat “browning” as a highly dynamic physiological process that the brain controls,” said Yang. “This work indicates that behavioral modifications promoted by the brain could influence how the amount of food we eat and store in fat is burned.”
Yang said hunger and cold exposure are two life-history variables during the development and evolution of mammals. “We observed that food deprivation dominates over cold exposure in neural control of white fat browning. This regulatory system may be evolutionarily important as it can reduce heat production to maintain energy balance when we are hungry. Modulating this brain-to-fat connection represents a potential novel strategy to combat obesity and associated illnesses.”
How female fruit flies know when to say ‘yes’
A fundamental question in neurobiology is how animals, including humans, make decisions. A new study publishing in the open access journal PLOS Biology on October 7 reveals how fruit fly females make a very important decision: to either accept or reject male courtship. This decision appears to be generated by a very small number of excitatory neurons that use acetylcholine as their neurotransmitter located in three brain regions. This study provides the framework to understand how decisions are generated and suggests that a decision is reached because that option is literally the most exciting.
How Rabies “Hijacks” Neurons to Attack the Brain
Rabies causes acute inflammation of the brain, producing psychosis and violent aggression. The virus, which paralyzes the body’s internal organs, is always deadly for those unable to obtain vaccines in time. Some 55,000 people die from rabies every year.
For the first time, Tel Aviv University scientists have discovered the exact mechanism this killer virus uses to efficiently enter the central nervous system, where it erupts in a toxic explosion of symptoms. The study, published in PLOS Pathogens, was conducted by Dr. Eran Perlson and Shani Gluska of TAU’s Sackler Faculty of Medicine and Sagol School of Neuroscience, in collaboration with the Friedrich Loeffler Institute in Germany.
"Rabies not only hijacks the nervous system’s machinery, it also manipulates that machinery to move faster," said Dr. Perlson. "We have shown that rabies enters a neuron in the peripheral nervous system by binding to a nerve growth factor receptor, responsible for the health of neurons, called p75. The difference is that its transport is very fast, even faster than that of its endogenous ligand, the small molecules that travel regularly along the neuron and keep the neuron healthy."
Faster than a speeding train
To track the rabies virus in the nervous system, the researchers grew mouse sensory neurons in an observation chamber and used live cell imaging to track the path taken by the virus particles. The researchers “saw” the virus hijack the “train” transporting cell components along a neuron and drove it straight into the spinal cord. Once in the spinal cord, the virus caught the first available train to the brain, where it wrought havoc before speeding through the rest of the body, shutting it down organ by organ.
Nerve cells, or neurons, outside the central nervous system are highly asymmetric. A long protrusion called an axon extends from the cell body to another nerve cell or organ along a specific transmission route. In addition to rapid transmission of electric impulses, axons also transport molecular materials over these distances.
"Axonal transport is a delicate and crucial process for neuronal survival, and when disrupted it can lead to neurodegenerative diseases," said Dr. Perlson. "Understanding how an organism such as rabies manipulates this machinery may help us in the future to either restore the process or even to manipulate it to our own therapeutic needs."
Hijacking the hijacker
"A tempting premise is to use this same machinery to introduce drugs or genes into the nervous system," Dr. Perlson added. By shedding light on how the virus hijacks the transport system in nerve cells to reach its target organ with maximal speed and efficiency, the researchers hope their findings will allow scientists to control the neuronal transport machinery to treat rabies and other neurodegenerative diseases.
Disruptions of the neuron train system also contribute to neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). According to Dr. Perlson, “An improved understanding of how the neuron train works could lead to new treatments for these disorders as well.”
(Image caption: 3D image of the hippocampus of a rat. Credit: M. Pyka)
People who wish to know how memory works are forced to take a glimpse into the brain. They can now do so without bloodshed: RUB researchers have developed a new method for creating 3D models of memory-relevant brain structures. They published their results in the trade journal “Frontiers in Neuroanatomy”.
Sea Horse gave the hippocampus the name
The way neurons are interconnected in the brain is very complicated. This holds especially true for the cells of the hippocampus. It is one of the oldest brain regions and its form resembles a sea horse (hippocampus in Latin). The hippocampus enables us to navigate space securely and to form personal memories. So far, the anatomic knowledge of the networks inside the hippocampus and its connection to the rest of the brain has left scientists guessing which information arrived where and when.
Signals spread through the brain
Accordingly, Dr Martin Pyka and his colleagues from the Mercator Research Group have developed a method which facilitates the reconstruction of the brain’s anatomic data as a 3D model on the computer. This approach is quite unique, because it enables automatic calculation of the neural interconnection on the basis of their position inside the space and their projection directions. Biologically feasible network structures can thus be generated more easily than it used to be the case with the method available to date. Deploying 3D models, the researchers use this technique to monitor the way neural signals spread throughout the network time-wise. They have, for example, found evidence that the hippocampus’ form and size could explain why neurons in those networks fire in certain frequencies.
Information become memories
In future, this method may help us understand how animals, for example, combine various information to form memories within the hippocampus, in order to memorise food sources or dangers and to remember them in certain situations.
(Fig. 1: Two-photon image of the three types of cells in the visual cortex of a rat. Neuronal activity is measured via changes in fluorescence intensity. Green cells are inhibitory neurons, white cells are excitatory neurons, and red cells are astrocytes.)
The ways that neurons in the brain respond to a given stimulus depends on whether an organism is asleep, drowsy, awake, paying careful attention or ignoring the stimulus. However, while the properties of neural circuits in the visual cortex are well known, the mechanisms responsible for the different patterns of activity in the awake and drowsy states remain poorly understood. A team of researchers led by Tadaharu Tsumoto from the RIKEN Brain Science Institute has observed the changes in activity that occur in rodents on waking from anesthesia.
The research team used a technique called two-photon functional calcium imaging to observe the activity of cells in the visual cortex of rats while they are anesthetized and exposed to a visual stimulus of an image moving across a screen. Using rats with inhibitory neurons labeled with a green fluorescent protein, the researchers were able to measure the activity separately in populations of inhibitory and excitatory neurons (Fig. 1). The neuronal activity in response to visual stimulation under anesthesia was recorded, and then the rats were allowed to wake and the change in activity of the two populations of neurons was observed.
Tsumoto’s team found that inhibitory neurons responded more reliably and with stronger activity to visual stimuli in the awake state than in the anesthetized state. The response of the excitatory neurons had a shorter decay time in the awake state, which means that their activity was more tightly linked to the presentation of the visual stimulus than when the animal was under the influence of anesthesia.
These changes that occur during wakefulness allow neurons in the visual cortex to respond more reliably to visual stimuli in their environment. “If animals are awakened from the drowsy state by howls or footsteps of enemies, the sensitivity or resolution of moving visual stimuli will increase so that they can more effectively judge how fast and from which location the enemies are coming,” explains Tsumoto.
The team then found that the basal forebrain region of the brain, which is known to play a role in state-dependent changes in cortical activity through its acetylcholine neurons, is responsible for these shifts in responses of neurons in the visual cortex of mice during wakefulness. They found that stimulating the basal forebrain of anesthetized animals could make visual cortical neurons take on the firing properties of the awake state. These findings highlight the role of the basal forebrain in modulating the responses of visual cortical neurons during wakefulness.