Posts tagged neuron
Articles and news from the latest research reports.
How Cells in the Nose Detect Odors
Now a team of scientists, led by neurobiologists at the University of California, Riverside, has an explanation. Focusing on the olfactory receptor for detecting carbon dioxide in Drosophila (fruit fly), the researchers identified a large multi-protein complex in olfactory neurons, called MMB/dREAM, that plays a major role in selecting the carbon dioxide receptors to be expressed in appropriate neurons.
Study results appear in the Nov. 15 issue of Genes & Development. The research is featured on the cover of the issue.
According to the researchers, a molecular mechanism first blocks the expression of most olfactory receptor genes (~60) in the fly’s antennae. This mechanism, which acts like a brake, relies on repressive histones —proteins that tightly wrap DNA around them. All insects and mammals are equipped with this mechanism, which keeps the large families of olfactory receptor genes repressed.
“How, then, do you release this brake so that only the carbon dioxide receptor is expressed in the carbon dioxide neuron while the remaining receptors are repressed?” said Anandasankar Ray, an assistant professor of entomology, whose lab conducted the research. “Our lab, in collaboration with a lab at Stanford University, has found that the MMB/dREAM multi-protein complex can act on the genes of the carbon dioxide receptors and de-repress the braking mechanism — akin to taking the foot off the brake pedal. This allows these neurons to express the receptors and respond to carbon dioxide.”
Ray explained that one way to understand the mechanism in operation is to consider a typewriter. When none of the keys are pressed, a spring mechanism or “brake” can be imagined to hold the type bars away from the paper. When a key is pressed, however, the brake on that key is overcome and the appropriate letter is typed onto the paper. And just as typing only one letter in one spot is important for each letter to be recognized, expressing one receptor in one neuron lets different sensor types to be generated in the nose.
Bluebrain is a ten-year documentary film-in-the-making about the twenty-first century race to reverse engineer the human brain. Such is the goal of The Blue Brain Project, based in Lausanne, Switzerland, one of the highest-profile neuroscience projects in the world today. Blue Brain’s audacious leader is Henry Markram, who publicly announced in 2009 that he seeks to reverse-engineer a human brain with digital simulations of all the physical properties of every neuron, powered by IBM supercomputers, by 2020. Director Noah Hutton began shooting in 2009, focusing exclusively on Markram’s Blue Brain Project— but starting in Year 3, the scope of the film has expanded to include the work of other prominent projects and labs seeking to understand the brain through different methods, including Sebastian Seung of M.I.T., Rafael Yuste of Columbia University, and Jeff Lichtman of Harvard University.
The film will continue to survey the work of other projects and their leaders in years to come, with yearly shorts released ahead of a full re-edit into a documentary feature due for completion in 2020. As the Blue Brain simulation is built over the course of this decade, so too will this documentary about a historic quest in human history. Through yearly updates from Blue Brain and other prominent scientists, philosophers, and ethicists, Bluebrain will track a crucial decade in the human mind’s relentless drive to understand itself.
Newborn Neurons — Even in the Adult Aging Brain - are Critical for Memory
Newly generated, or newborn neurons in the adult hippocampus are critical for memory retrieval, according to a study led by Stony Brook University researchers published online in Nature Neuroscience. The functional role of newborn neurons in the brain is controversial, but in “Optical controlling reveals time-dependent roles for adult-born dentate granule cells,” the researchers detail that by ‘silencing’ newborn neurons, memory retrieval was impaired. The findings support the idea that the generation of new neurons in the brain may be crucial to normal learning and memory processes.
Previous research by the study’s lead investigator Shaoyu Ge, PhD, Assistant Professor in the Department of Neurobiology & Behavior at Stony Brook University, and others have demonstrated that newborn neurons form connections with existing neurons in the adult brain. To help determine the role of newborn neurons, Dr. Ge and colleagues devised a new optogenetic technique to control newborn neurons and test their function in the hippocampus, one of the regions of the brain that generates new neurons, even in the adult aging brain.
“Significant controversy has surrounded the functional role of newborn neurons in the adult brain,” said Dr. Ge. “We believe that our study results provide strong support to the idea that new neurons are important for contextual fear memory and spatial navigation memory, two essential aspects of memory and learning that are modified by experience.
“Our findings could also shed light on the diagnosis and treatment of conditions common to the adult aging brain, such as dementia and Alzheimer’s disease,” he said.
A better brain implant: Slim electrode cozies up to single neurons
A thin, flexible electrode developed at the University of Michigan is 10 times smaller than the nearest competition and could make long-term measurements of neural activity practical at last.
This kind of technology could eventually be used to send signals to prosthetic limbs, overcoming inflammation larger electrodes cause that damages both the brain and the electrodes.
The main problem that neurons have with electrodes is that they make terrible neighbors. In addition to being enormous compared to the neurons, they are stiff and tend to rub nearby cells the wrong way. The resident immune cells spot the foreigner and attack, inflaming the brain tissue and blocking communication between the electrode and the cells.
The new electrode developed by the teams of Daryl Kipke, a professor of biomedical engineering, Joerg Lahann, a professor of chemical engineering, and Nicholas Kotov, the Joseph B. and Florence V. Cejka Professor of Engineering, is unobtrusive and even friendly in comparison. It is a thread of highly conductive carbon fiber, coated in plastic to block out signals from other neurons. The conductive gel pad at the end cozies up to soft cell membranes, and that close connection means the signals from brain cells come in much clearer.
"It’s a huge step forward," Kotov said. "This electrode is about seven microns in diameter, or 0.007 millimeters, and its closest competitor is about 25 to 100 microns."
Inflammation for Regeneration
The secret to zebrafish’s remarkable capacity for repairing their brains is inflammation, according to a report published online in Science. Neural stem cells in the fish’s brains express a receptor for inflammatory signaling molecules, which prompt the cells to multiply and develop into new neurons.
“This is a very interesting paper,” said Guo-li Ming, a professor of neurology and neuroscience at The Johns Hopkins University in Baltimore, who was not involved in the study. “It is well known that fish have this ability to self-repair, and this paper provides a mechanism,” she said.
Zebrafish, like many other vertebrates, are able to regenerate a variety of body tissues, including their brains. In fact, said Michael Brand, a professor of developmental genetics at the Technische Universität in Dresden, Germany, “mammals are the ones that seem to have lost this ability—they are kind of the odd ones out.” Given the therapeutic potential of neuron regeneration for patients with brain or spinal injuries, “we’d like to figure out if we can somehow reactivate this potential in humans,” Brand said.
Dramatic expansion of the human cerebral cortex, over the course of evolution, accommodated new areas for specialized cognitive function, including language. Understanding the genetic mechanisms underlying these changes, however, remains a challenge to neuroscientists.
A team of researchers in Japan, led by Hideyuki Okano of Keio University School of Medicine and Tomomi Shimogori of the RIKEN Brain Science Institute, has now elucidated the mechanisms of cortical evolution. They used molecular techniques to compare the gene expression patterns in mouse and monkey brains.
Using the technique called in situ hybridization to visualize the distribution of mRNA transcripts, Okano, Shimogori and their colleagues examined the expression patterns of genes that are known to regulate development of the mouse brain. They compared these patterns to those of the same genes in the brain of the common marmoset. They found that most of the genes had similar expression patterns in mice and marmosets, but that some had strikingly different patterns between the two species. Notably, some areas of the visual and prefrontal cortices showed expression patterns that were unique to marmosets.
The researchers also found differences in gene expression within regions that connect the prefrontal cortex and hippocampus, a structure that is critical for learning and memory.
Scripps Research Institute Scientists Uncover a New Pathway that Regulates Information Processing in the Brain
Scientists at The Scripps Research Institute (TSRI) have identified a new pathway that appears to play a major role in information processing in the brain. Their research also offers insight into how imbalances in this pathway could contribute to cognitive abnormalities in humans.
The study, published in the November 9, 2012 issue of the journal Cell, focuses on the actions of a protein called HDAC4. The researchers found that HDAC4 is critically involved in regulating genes essential for communication between neurons.
“We found that HDAC4 represses these genes, and its function in a given neuron is controlled by activity of other neurons forming a circuit,” said TSRI Assistant Professor Anton Maximov, senior investigator for the study.
Hunting neuron killers in Alzheimer’s and TBI
Sanford-Burnham researchers discovered that the protein appoptosin prompts neurons to commit suicide in several neurological conditions—giving them a new therapeutic target for Alzheimer’s disease and traumatic brain injury.
Dying neurons lead to cognitive impairment and memory loss in patients with neurodegenerative disorders–conditions like Alzheimer’s disease and traumatic brain injury. To better diagnose and treat these neurological conditions, scientists first need to better understand the underlying causes of neuronal death.
Enter Huaxi Xu, Ph.D., professor in Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center. He and his team have been studying the protein appoptosin and its role in neurodegenerative disorders for the past several years. Appoptosin levels in the brain skyrocket in conditions like Alzheimer’s and stroke, and especially following traumatic brain injury.
Appoptosin is known for its role in helping the body make heme, the molecule that carries iron in our blood (think “hemoglobin,” which makes blood red). But what does heme have to do with dying brain cells? As Xu and his group explain in a paper they published recently in the Journal of Neuroscience, excess heme leads to the overproduction of reactive oxygen species, which include cell-damaging free radicals and peroxides, and triggers apoptosis, the carefully regulated process of cellular suicide. This means that more appoptosin and more heme cause neurons to die.
Not only did Xu and his team unravel this whole appoptosin-heme-neurodegeneration mechanism, but when they inhibited appoptosin in laboratory cell cultures, they noticed that the cells didn’t die. This finding suggests that appoptosin might make an interesting new therapeutic target for neurodegenerative disorders.
What’s next? Xu and colleagues are now probing appoptosin’s function in mouse models. They’re also looking for new therapies that target the protein.
“Since the upregulation of appoptosin is important for cell death in diseases such as Alzheimer’s, we’re now searching for small molecules that modulate appoptosin expression or activity. We’ll then determine whether these compounds may be potential drugs for Alzheimer’s or other neurodegenerative diseases,” Xu explains.
Putting a stop to runaway appoptosin won’t be easy, though. That’s because we still need the heme-building protein to operate at normal levels for our blood to carry iron. In a previous study, researchers found that a mutation in the gene that encodes appoptosin causes anemia. “Too much of anything is bad, but so is too little,” Xu says.
New therapies that target neurodegenerative disorders and traumatic brain injury are sorely needed. According to the CDC, approximately 1.7 million people sustain a traumatic brain injury each year. It’s an acute injury, but one that can also lead to long-term problems, causing epilepsy and increasing a person’s risk for Alzheimer’s and Parkinson’s diseases. Not only has traumatic brain injury become a worrisome problem in youth and professional sports in recent years, the Department of Defense calls traumatic brain injury “one of the signature injuries of troops wounded in Afghanistan and Iraq.”
(Source: beaker.sanfordburnham.org)
The Mysterious Motivational Functions of Mesolimbic Dopamine
Nucleus accumbens dopamine is known to play a role in motivational processes, and dysfunctions of mesolimbic dopamine may contribute to motivational symptoms of depression and other disorders, as well as features of substance abuse. Although it has become traditional to label dopamine neurons as “reward” neurons, this is an overgeneralization, and it is important to distinguish between aspects of motivation that are differentially affected by dopaminergic manipulations. For example, accumbens dopamine does not mediate primary food motivation or appetite, but is involved in appetitive and aversive motivational processes including behavioral activation, exertion of effort, approach behavior, sustained task engagement, Pavlovian processes, and instrumental learning. In this review, we discuss the complex roles of dopamine in behavioral functions related to motivation.
Grid cell firing patterns signal environmental novelty by expansion
The hippocampal formation plays key roles in representing an animal’s location and in detecting environmental novelty to create or update those representations. However, the mechanisms behind this latter function are unclear. Here, we show that environmental novelty causes the spatial firing patterns of grid cells to expand in scale and reduce in regularity, reverting to their familiar scale as the environment becomes familiar. Simultaneously recorded place cell firing fields remapped and showed a smaller, temporary expansion. Grid expansion provides a potential mechanism for novelty signaling and may enhance the formation of new hippocampal representations, whereas the subsequent slow reduction in scale provides a potential familiarity signal.