Posts tagged neuron
Articles and news from the latest research reports.
First measurements made of key brain links
Until now, brain scientists have been almost completely in the dark about how most of the nonspecific thalamus interacts with the prefrontal cortex, a relationship believed to be key in such fundamental functions as maintaining consciousness and mental arousal. Brown University researchers performed a set of experiments, described in the Journal of Neuroscience, to explore and measure those circuits for the first time.
Dopamine Not About Pleasure (Anymore)
To John Salamone, professor of psychology and longtime researcher of the brain chemical dopamine, scientific research can be very slow-moving.
“It takes a long time for things to change in science,” he says. “It’s like pulling on the steering wheel of an ocean liner, then waiting for the huge ship to slowly turn.”
Salamone has spent most of his career battling a particular long-held scientific idea: the popular notion that high levels of brain dopamine are related to experiences of pleasure. As increasing numbers of studies show, he says, the famous neurotransmitter is not responsible for pleasure, but has to do with motivation.
He summarizes and comments on the evidence for this shift in thinking in a Nov. 8 review in the Cell Press journal Neuron.
Scientists describe the genetic signature of a vital set of neurons
Scientists at NYU Langone Medical Center have identified two genes involved in establishing the neuronal circuits required for breathing. They report their findings in a study published in the December issue of Nature Neuroscience. The discovery, featured on the journal’s cover, could help advance treatments for spinal cord injuries and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), which gradually kill neurons that control the movement of muscles needed to breathe, move, and eat.
The study identifies a molecular code that distinguishes a group of muscle-controlling nerve cells collectively known as the phrenic motor column (PMC). These cells lie about halfway up the back of the neck, just above the fourth cervical vertebra, and are “probably the most important motor neurons in your body,” says Jeremy Dasen, PhD, assistant professor of physiology and neuroscience and a member of the Howard Hughes Medical Institute, who led the three-year study with Polyxeni Philippidou, PhD, a postdoctoral fellow.
Harming the part of the spinal cord where the PMC resides can instantly shut down breathing. But relatively little is known about what distinguishes PMC neurons from neighboring neurons, and how PMC neurons develop and wire themselves to the diaphragm in the fetus.
The PMC cells relay a constant flow of electrochemical signals down their bundled axons and onto the diaphragm muscles, allowing the lungs to expand and relax in the natural rhythm of breathing. “We now have a set of molecular markers that distinguish those cells from other populations of motor neurons, so that we can study them in detail and look for ways to selectively enhance their survival,” Dr. Dasen says. Degeneration of PMC neurons is the primary cause of death in patients with ALS and spinal cord injuries.
To find out what distinguishes PMC neurons from their spinal neighbors in mice, Dr. Philippidou injected a retrograde fluorescent tracer into the phrenic nerve, which wires the PMC to the diaphragm, and then looked for the spinal neurons that lit up as the tracer worked its way back to the PMC. He used transgenic mice that express green fluorescent protein (GFP) in motor neurons and their axons in order to see the phrenic nerve. After noting the characteristic gene expression pattern of these PMC neurons, Dr. Philippidou began to determine their specific roles. Ultimately, a complicated strain of transgenic mice, based partly on mice supplied by collaborator Lucie Jeannotte, PhD, at the University of Laval in Quebec, revealed two genes, Hoxa5 and Hoxc5, as the prime controllers of proper PMC development. Hox genes (39 are expressed in humans) are well known as master gene regulators of animal development.
When Hoxa5 and Hoxc5 are silenced in embryonic motor neurons in mice, the scientists reported, the PMC fails to form its usual, tightly columnar organization and doesn’t connect correctly to the diaphragm, leaving a newborn animal unable to breathe. “Even if you delete these genes late in fetal development, the PMC neuron population drops and the phrenic nerve doesn’t form enough branches on diaphragm muscles,” Dr. Dasen says.
Dr. Dasen plans to use the findings to help understand the wider circuitry of breathing—including rhythm-generating neurons in the brain stem, which are in turn responsive to carbon dioxide levels, stress, and other environmental factors. “Now that we know something about PMC cells, we can work our way through the broader circuit, to try to figure out how all those connections are established,” he says.
"Once we understand how the respiratory network is wired we can begin to develop novel treatment options for breathing disorders such as sleep apneas," adds Dr. Philippidou.
In late October Dr. Dasen lost many of his transgenic mice when Hurricane Sandy flooded the basement of the Smilow building at NYU Langone Medical Center. But just before the hurricane hit, he sent an important group of these mice back to Dr. Jeannotte in Quebec, “so we didn’t lose everything,” he says.
(Source: eurekalert.org)
Researchers find fly receptor neurons able to communicate without synapse connections
Researchers at Yale University have found that neural receptors in a fly’s antenna are able to communicate with one another despite a lack of synaptic connections. They suggest in their paper published in the journal Nature that the communication between the neurons occurs via electrical signals transported by shared fluids.
Suspecting that the fluid filled hairs in the antennas of the fly, Drosophila melanogaster, called sensilla, might possess a property known as ephaptic coupling, where nerve cells communicate without a direct link, the researchers tested the abilities of several fly specimens in their lab. The first focused on two receptors located in the sensilla responsible for detecting fruity methyl hexanoate and banana-scented 2-heptanone, respectively. When exposed to methyl hexonate, they found that only the first receptor fired. If heptanone were suddenly introduced however, the first receptor ceased firing immediately as the second commenced indicating that some form of communication between the two was occurring. They found that the reverse worked as well. To rule out possible modes of communication, the researchers conducted the same experiment with flies that had their synapses disabled via drugs and with others that had had their antennas physically cut off. Both showed the same results indicating that the communication was not direct but was localized.
In another experiment the researchers blocked a neuron in a sensilla responsible for detecting vinegar which was situated next to a neuron responsible for detecting carbon dioxide (for avoidance). When placed in a maze with two arms that smelled of carbon dioxide and one of vinegar, the fly headed for the vinegar scented arm, showing that the vinegar disabled neuron was still able to communicate with its carbon dioxide detecting partner.
The researchers suggest such an ability in flies might help in figuring out which path to take when encountering an environment filled with many different options. They also suggest that neuron pairs in the sensilla might be communicating with one another via electrical signals. When one detects what it’s supposed to detect, it sends a small charge into the fluid in which it and other neurons reside. That charge may then cause other neurons in the vicinity to go silent.
(Source: medicalxpress.com)
Sophisticated worms
One cell does it all: Sensory input to motor output in extraordinary neuronIt’s one of the basic tenets of biological research — by studying simple “model” systems, researchers hope to gain insight into the workings of more complex organisms.
Caenorhabditis elegans — a tiny, translucent worm with just 302 neurons — has long been studied to understand how a nervous system is capable of translating sensory input into motion and behavior.
New research by the laboratory of Professor Aravi Samuel in the Harvard Physics Department and the Center for Brain Sciences, however, is uncovering surprising sophistication in the individual neurons of the worm’s “simple” nervous system.
Quan Wen, a postdoctoral fellow in the Samuel lab who spearheaded the research, has shown that a single type of neuron in the C. elegans nerve cord (the worm equivalent of the spinal cord) packs both sensory and motor capabilities. The locomotory systems of most creatures, including humans, use different neurons to gather sensory information about animal movement or to send signals to muscle cells. C. elegans encodes an entire sensorimotor loop into one particularly sophisticated type of motor neuron. The work is described in the journal Neuron.
“This type of circuit is completely new — this is not the way people think about any motor circuit,” Samuel said.
The discovery arose from researchers asking a simple question: How does C. elegans organize its movements?
“What sent us down this road was a phenomenon that we’ve observed in the lab,” Samuel explained. “If we place the worms in a wet environment, they will swim. On surfaces, however, they crawl. The question was how the animal ‘knew’ to do each. The answer had to be feedback: Something is telling the worm that it’s in a low-viscous environment here, and a high-viscous environment there.
“The general name for this is ‘proprioceptive feedback,’ ” Samuel continued. “It’s that process that allows your brain to understand what each of your legs is doing and coordinate your ability to walk, it gives you an awareness of your body posture. The real puzzle in this case, however, was that C. elegans has so few neurons … we didn’t understand how proprioceptive feedback could come back into the system.”
(Image credit: snickclunk)
A 3-D Light Switch for the Brain
A new tool for neuroscientists delivers a thousand pinpricks of light to a chunk of gray matter smaller than a sugar cube. The new fiber-optic device, created by biologists and engineers at the Massachusetts Institute of Technology (MIT) in Cambridge, is the first tool that can deliver precise points of light to a 3-D section of living brain tissue. The work is a step forward for a relatively new but promising technique that uses gene therapy to turn individual brain cells on and off with light.
Scientists can use the new 3-D “light switch” to better understand how the brain works. It might also be used one day to create neural prostheses that could treat conditions such as Parkinson’s disease and epilepsy. The researchers describe their device in a paper published today in the Optical Society’s (OSA) journal Optics Letters.
The technique of manipulating neurons with light is only a few years old, but the authors estimate that thousands of scientists are already using this technology, called optogenetics, to study the brain. In optogenetics, researchers first sensitize select cells in the brain to a particular color of light. Then, by illuminating precise areas of the brain, they are able to selectively activate or deactivate the individual neurons that have been sensitized.
Ed Boyden, a synthetic biologist at MIT and co-lead researcher on the paper, is a pioneer of this emerging field, which he says offers the ability to probe connections in the brain.
"You can see neural activity in the brain that is associated with specific behaviors," Boyden says, “but is it important? Or is it a passive copy of important activity located elsewhere in the brain? There’s no way to know for sure if you just watch.” Optogenetics allows scientists to play a more active role in probing the brain’s connections, to fire up one type of cell or deactivate another and then observe the effect on a behavior, such as quieting a seizure.
Unlike the previous, 1-D versions of this light-emitting device, the new tool delivers light to the brain in three dimensions, opening the potential to explore entire circuits within the brain. So far, the 3-D version has been tested in mice, although Boyden and colleagues have used earlier optogenetic technologies with non-human primates as well.
Optogenetics illuminates pathways of motivation through brain
Whether you are an apple tree or an antelope, survival depends on using your energy efficiently. In a difficult or dangerous situation, the key question is whether exerting effort — sending out roots in search of nutrients in a drought or running at top speed from a predator — will be worth the energy.
In a paper published online Nov. 18 in Nature, Karl Deisseroth, MD, PhD, a professor of bioengineering and of psychiatry and behavioral sciences at Stanford University, and postdoctoral scholar Melissa Warden, PhD, describe how they have isolated the neurons that carry these split-second decisions to act from the higher brain to the brain stem. In doing so, they have provided insight into the causes of severe brain disorders such as depression.
In organisms as complex as humans, the neural mechanisms that help answer the question, “Is it worth my effort?” can fail, leading to debilitating mental illnesses. Major depressive disorder, for instance, which affects nearly 20 percent of people at some point in life, is correlated with underperformance in the parts of the brain involved in motivation. But researchers have struggled to work out the exact cause and effect.
“It’s challenging because we do not have a fundamental understanding of the circuitry that controls this sort of behavioral pattern selection. We don’t understand what the brain is doing wrong when these behaviors become dysfunctional, or even what the brain is supposed to be doing when things are working right,” Deisseroth said. “This is the level of the mystery we face in this field.”
Clinicians refer to this slowing down of motivation in depressed patients as “psychomotor retardation.” According to Deisseroth, who is also a practicing psychiatrist, patients may experience this symptom mentally, finding it hard to envision the positive results of an action, or, he said, they may feel physically heavy, like their limbs just do not want to move.
“This is one of the most debilitating aspects of depression, and motivation to take action is something that we can model in animals. That’s the exciting opportunity for us as researchers,” said Deisseroth, who also holds the D.H. Chen Professorship.
Zooming in on the human brain
A visually compelling tour of the human brain, from anatomy to cells to genes and back.
Functional Connectivity and Tuning Curves in Populations of Simultaneously Recorded Neurons
How interactions between neurons relate to tuned neural responses is a longstanding question in systems neuroscience. Here we use statistical modeling and simultaneous multi-electrode recordings to explore the relationship between these interactions and tuning curves in six different brain areas. We find that, in most cases, functional interactions between neurons provide an explanation of spiking that complements and, in some cases, surpasses the influence of canonical tuning curves. Modeling functional interactions improves both encoding and decoding accuracy by accounting for noise correlations and features of the external world that tuning curves fail to capture. In cortex, modeling coupling alone allows spikes to be predicted more accurately than tuning curve models based on external variables. These results suggest that statistical models of functional interactions between even relatively small numbers of neurons may provide a useful framework for examining neural coding.
Parkinson’s Disease Protein Causes Disease Spread and Neuron Death in Healthy Animals
Understanding how any disease progresses is one of the first and most important steps towards finding treatments to stop it. This has been the case for such brain-degenerating conditions as Alzheimer’s disease. Now, after several years of incremental study, researchers at the Perelman School of Medicine, University of Pennsylvania have been able to piece together important steps in how Parkinson’s disease (PD) spreads from cell to cell and leads to nerve cell death.
Their line of research also informs the general concept that this type of disease progression is a common pathway for such other neurodegenerative diseases as Alzheimer’s, Huntington’s, progressive supranuclear palsy, and possibly amyotrophic lateral sclerosis (ALS).
The Penn team found that injecting synthetic, misfolded and fibrillar α-Synuclein (α-Syn) – the PD disease protein — into the brains of normal, “wild-type” mice recapitulates the cascade of cellular demise seen in human PD patients.
Parkinson’s disease is characterized by abundant α-Syn clumps in neurons and the massive loss of midbrain dopamine-producing neurons. However, a cause-and-effect relationship between the formation of α-Syn clumps and neurodegeneration has been unclear.
In short, the Penn researchers found that, in healthy mice, a single injection of synthetic, misfolded α-Syn fibrils led to a cell-to-cell transmission of pathologic α-Syn proteins and the formation of Parkinson’s α-Syn clumps known as Lewy bodies in interconnected regions of the brain. Their findings appear in this week’s issue of Science. The team was led by senior author Virginia M.-Y Lee, PhD, director of the Center for Neurodegenerative Disease Research (CNDR) and professor of Pathology and Laboratory Medicine, and first author Kelvin C. Luk, PhD, research assistant professor in the CNDR.