Posts tagged neuroscience
Articles and news from the latest research reports.
(Image caption: A peptide responsible for cell communication in the brain, Vip (green) is reduced in the brains of mice that have little or no Lhx1 (right). Credit: Salk Institute for Biological Studies)
Scientists at the Salk Institute for Biological Studies have identified a gene that regulates sleep and wake rhythms.
The discovery of the role of this gene, called Lhx1, provides scientists with a potential therapeutic target to help night-shift workers or jet lagged travelers adjust to time differences more quickly. The results, published in eLife, can point to treatment strategies for sleep problems caused by a variety of disorders.
“It’s possible that the severity of many dementias comes from sleep disturbances,” says Satchidananda Panda, a Salk associate professor who led the research team. “If we can restore normal sleep, we can address half of the problem.”
Every cell in the body has a “clock” – an abundance of proteins that dip or rise rhythmically over approximately 24 hours. The master clock responsible for establishing these cyclic circadian rhythms and keeping all the body’s cells in sync is the suprachiasmatic nucleus (SCN), a small, densely packed region of about 20,000 neurons housed in the brain’s hypothalamus.
More so than in other areas of the brain, the SCN’s neurons are in close and constant communication with one another. This close interaction, combined with exposure to light and darkness through vision circuits, keeps this master clock in sync and allows people to stay on essentially the same schedule every day. The tight coupling of these cells also helps make them collectively resistant to change. Exposure to light resets less than half of the SCN cells, resulting in long periods of jet lag.
In the new study, researchers disrupted the light-dark cycles in mice and compared changes in the expression of thousands of genes in the SCN with other mouse tissues. They identified 213 gene expression changes that were unique to the SCN and narrowed in on 13 of these that coded for molecules that turn on and off other genes. Of those, only one was suppressed in response to light: Lhx1.
“No one had ever imagined that Lhx1 might be so intricately involved in SCN function,” says Shubhroz Gill, a postdoctoral researcher and co-first author of the paper. Lhx1 is known for its role in neural development: it’s so important, that mice without the gene do not survive. But this is the first time it has been identified as a master regulator of light-dark cycle genes.
By recording electrical activity in the SCN of animals with reduced amounts of the Lhx1 protein, the researchers saw that the SCN neurons weren’t in sync with one another, despite appearing rhythmic individually.
“It was all about communication–the neurons were not talking to each other without this molecule,” says Ludovic Mure, a postdoctoral researcher and an author on the paper. A next step in the work will be to understand exactly how Lhx1 affects the expression of genes that creates this synchronicity.
Studying a mouse version of jet lag–an 8-hour shift in their day-night cycle–the scientists found that those with little or no Lhx1 readjusted much faster to the shift than normal mice. This suggests that because these neurons are less in sync with one another, they are more easily able to shift to a new schedule, though it is difficult for them to maintain that schedule, Panda says.
These mice also exhibited reduced activity of certain genes, including one that creates vasoactive intestinal peptide or Vip, a molecule that has important roles in development and as a hormone in the intestine and blood. In the brain, Vip affects cell communication, but nobody had known that Lhx1 regulated it until now, Panda says. Interestingly, the team also found that adding Vip restored cell synchrony in the SCN.
“This approach helped us to close that knowledge gap and show that Vip is a very important protein, at least for SCN,” Panda says. “It can compensate for the loss of Lhx1.”
On the other hand, cutting back on Vip could be another way to treat jet lag. Vip could be an even easier drug target compared with Lhx1 because Vip is secreted from cells rather than inside cells, Panda says. “If we find a drug that will block the Vip receptor or somehow break down Vip, then maybe that will help us reset the clock much faster,” he adds.
The new results take the group a step closer to their goal of creating cell regenerative therapies that restore the SCN and ameliorate sleep problems. The scientists have made their gene expression data available through a searchable web interface at http://scn.salk.edu, giving other researchers a handy way to explore the effect of light and dark in genes in the SCN and other tissues.
Vajrayana Meditation Techniques Associated with Tibetan Buddhism Can Enhance Brain Performance
Contrary to popular belief, not all meditation techniques produce similar effects of body and mind. Indeed, a recent study by researchers from the National University of Singapore (NUS) has demonstrated for the first time that different types of Buddhist meditation – namely the Vajrayana and Theravada styles of meditation - elicit qualitatively different influences on human physiology and behaviour, producing arousal and relaxation responses respectively.
In particular, the NUS research team found that Vajrayana meditation, which is associated with Tibetan Buddhism, can lead to enhancements in cognitive performance.
The study by Associate Professor Maria Kozhevnikov and Dr Ido Amihai from the Department of Psychology at the NUS Faculty of Arts and Social Sciences was first published in the journal PLOS ONE in July 2014.
Vajrayana and Theravada meditation produce different physiological responses
Previous studies had defined meditation as a relaxation response and had attempted to categorise meditation as either involving focused or distributed attentional systems. Neither of these hypotheses received strong empirical support, and most of the studies focused on Theravada meditative practices.
Assoc Prof Kozhevnikov and Dr Amihai examined four different types of meditative practices: two types of Vajrayana meditations (Tibetan Buddhism) practices (Visualisation of self-generation-as-Deity and Rig-pa) and two types of Theravada practices (Shamatha and Vipassana). They collected electrocardiographic (EKG) and electroencephalographic (EEG) responses and also measured behavioural performance on cognitive tasks using a pool of experienced Theravada practitioners from Thailand and Nepal, as well as Vajrayana practitioners from Nepal.
They observed that physiological responses during the Theravada meditation differ significantly from those during the Vajrayana meditation. Theravada meditation produced enhanced parasympathetic activation (relaxation). In contrast, Vajrayana meditation did not show any evidence of parasympathetic activity but showed an activation of the sympathetic system (arousal).
The researchers had also observed an immediate dramatic increase in performance on cognitive tasks following only Vajrayana styles of meditation. They noted that such dramatic boost in attentional capacity is impossible during a state of relaxation. Their results show that Vajrayana and Theravada styles of meditation are based on different neurophysiological mechanisms, which give rise to either an arousal or relaxation response.
Applications of the research findings
The findings from the study showed that Vajrayana meditation can lead to dramatic enhancement in cognitive performance, suggesting that Vajrayana meditation could be especially useful in situations where it is important to perform at one’s best, such as during competition or states of urgency. On the other hand, Theravada styles of meditation are an excellent way to decrease stress, release tension, and promote deep relaxation.
Further research
After seeing that even a single session of Vajrayana meditation can lead to radical enhancements in brain performance, Assoc Prof Kozhevnikov and Dr Amihai will be investigating whether permanent changes could occur after long-term practice. The researchers are also looking at how non-practitioners can benefit from such meditative practices.
Assoc Prof Kozhevnikov said, “Vajrayana meditation typically requires years of practice, so we are also looking into whether it is also possible to acquire the beneficial effects of brain performance by practicing certain essential elements of the meditation. This would provide an effective and practical method for non-practitioners to quickly increase brain performance in times of need.”
(Image caption: Engineers have developed a new microscopy method that uses a fine needle or cannula and an LED light to make 3-D images. They hope this new microscope technology, shown here, can be implanted into the brains of mice to show images of cells. Credit: Ganghun Kim, University of Utah)
3-D Microscope Method to Look Inside Brains
A University of Utah team discovered a method for turning a small, $40 needle into a 3-D microscope capable of taking images up to 70 times smaller than the width of a human hair. This new method not only produces high-quality images comparable to expensive microscopes, but may be implanted into the brains of living mice for imaging at the cellular level.
The study appears in the Aug. 18 issue of the journal Applied Physics Letters.
Designed by Rajesh Menon, an associate professor of electrical and computer engineering, and graduate student Ganghun Kim, the microscope technique works when an LED light is illuminated and guided through a fiberoptic needle or cannula. Returned pictures are reconstructed into 3-D images using algorithms developed by Menon and Kim.
“Unlike miniature microscopes, our approach does not use optics,” Menon says. “It’s primarily computational.”
He says this approach will allow researchers not only to take images far smaller than those taken by current miniature microscopes, but do it for a fraction of the cost.
“We can get approximately 1-micron-resolution images that only $250,000 and higher microscopes are capable of generating,” Menon says. “Miniature microscopes are limited to the few tens of microns.”
Menon hopes to extend the technology in the future so it can see details down to submicron resolutions, compared with the current 1.4 microns. (A micron is a millionth of a meter. A human hair is about 100 microns wide.)
The microscope was originally designed for the lab of Nobel Prize-winning U human genetics professor, Mario R. Capecchi, whose team will use it to observe the brains of living mice to gain insight into how certain proteins in the brain react to various stimuli. Because the microscope can be assembled so inexpensively and easily go into hard-to-reach places, Menon and Kim expect many other uses for the device.
“This microscope will open up new avenues of research,” Menon says. “Its low-cost, small-size, large field-of-view and implantable features will allow researchers to use this in fields ranging from biochemistry to mining.”
Hijacking the brain’s blood supply: Tumor discovery could aid treatment
Dangerous brain tumors hijack the brain’s existing blood supply throughout their progression, by growing only within narrow potential spaces between and along the brain’s thousands of small blood vessels, new research shows for the first time.
(Caption: This microscopic view of a mouse brain tumor shows small clusters of tumor cells (in green), marked with white arrows, growing along tiny blood vessels (in red) in the brain and filling the space in between the vessels.)
The findings contradict the concept that brain tumors need to grow their own blood vessels to keep themselves growing – and help explain why drugs that aim to stop growth of the new blood vessels have failed in clinical trials to extend the lives of patients with the worst brain tumors.
In fact, trying to block the growth of new blood vessels in the brain actually spurs malignant tumors called gliomas to grow faster and further, the research shows. On the hopeful side, the research suggests a new avenue for finding better drugs.
The discoveries come from a University of Michigan Medical School team studying tumors in rodents and humans, and advanced computer models, in collaboration with colleagues from Arizona State University. Published online in the journal Neoplasia, they’ll be featured as the journal’s cover article later this month.
Focal blood-brain-barrier disruption with high-frequency pulsed electric fields
A team of researchers from the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences have developed a new way of using electricity to open the blood-brain-barrier (BBB). The Vascular Enabled Integrated Nanosecond pulse (VEIN pulse) procedure consists of inserting minimally invasive needle electrodes into the diseased tissue and applying multiple bursts of nanosecond pulses with alternating polarity. It is thought that the bursts disrupt tight junction proteins responsible for maintaining the integrity of the BBB without causing damage to the surrounding tissue. This technique is being developed for the treatment of brain cancer and neurological disorders, such as Parkinson’s disease, and is set to appear in the upcoming issue of the journal TECHNOLOGY.
(Caption: Two, minimally invasive needle electrodes with 1 mm active length were spaced 4.0 mm apart and inserted into the right cerebral hemisphere 1.5 mm beneath the surface of the dura. A burst of 200, 500 ns duration square pulses of alternating polarity with a voltage-to-distance ratio of 250 V/cm were applied through the electrodes. In the case shown above, bursts were repeated once per second for 10 min. The extent of BBB disruption is shown by the dotted line surrounding Evans blue-albumin complex uptake on the gross brain slice preparation (left) and the corresponding fluorescent image (middle). Additionally, areas of BBB disruption appear as hyperintense (white) on the T1-weighted MRI exam, due to the uptake of a gadolinium-Evans blue tracer. Scale bar represents 5 mm. Credit: John H. Rossmeisl Jr., Neurology and Neurosurgery, Virginia-Maryland Regional College of Veterinary Medicine and Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences).
The BBB is a network of tight junctions that normally acts to protect the brain from foreign substances by preventing them from leaking out of blood vessels. However, it also limits the effectiveness of drugs to treat brain disease. Temporarily opening the BBB is a way to ensure that drugs can still be effective.
For the treatment of brain cancer, “VEIN pulses could be applied at the same time as biopsy or through the same track as the biopsy probe in order to mitigate damage to the healthy tissue by limiting the number of needle insertions,” says Rafael V. Davalos, Ph.D, director of the Bioelectromechanical Systems Laboratory at Virginia Tech.
Additionally, the group shows that VEIN pulses can be applied without causing muscle contractions, which may dislodge the electrodes and require the use of a neuroblocker and general anesthesia. According to Christopher B. Arena, Ph.D., co-lead author on the paper with Paulo A. Garcia, Ph.D. and Michael B. Sano, Ph.D., “the fact that the pulses alternate in polarity helps to avoid unwanted, electrically induced movement. Therefore, it could be possible to perform this procedure without using a neuroblocker and with patients under conscious sedation. This is similar to how deep brain stimulation is implemented clinically to treat Parkinson’s disease.”
The team now plans to translate the technology into clinical applications through a university spin-out company, VoltMed, Inc.
Biomarker Could Reveal Why Some Develop Post-Traumatic Stress Disorder
Blood expression levels of genes targeted by the stress hormones called glucocorticoids could be a physical measure, or biomarker, of risk for developing Post-Traumatic Stress Disorder (PTSD), according to a study conducted in rats by researchers at the Icahn School of Medicine at Mount Sinai and published August 11 in Proceedings of the National Academy of Sciences (PNAS). That also makes the steroid hormones’ receptor, the glucocorticoid receptor, a potential target for new drugs.
Post-Traumatic Stress Disorder (PTSD) is triggered by a terrifying event, either witnessed or experienced. Symptoms may include flashbacks, nightmares and severe anxiety, as well as uncontrollable thoughts about the event. Not everyone who experiences trauma develops PTSD, which is why the study aimed to identify biomarkers that could better measure each person’s vulnerability to the disorder.
“Our aim was to determine which genes are differentially expressed in relation to PTSD,” said lead investigator Rachel Yehuda, PhD, Professor of Psychiatry and Neuroscience and Director of the Traumatic Stress Studies Division at the Icahn School of Medicine at Mount Sinai. “We found that most of the genes and pathways that are different in PTSD-like animals compared to resilient animals are related to the glucocorticoid receptor, which suggests we might have identified a therapeutic target for treatment of PTSD,” said Dr. Yehuda, who also heads the Mental Health Patient Care Center and PTSD Research Program at the James J. Peters Veterans Affairs Medical Center in the Bronx.
The research team exposed a group of male and female rats to litter soiled by cat urine, a predatory scent that mimics a life-threatening situation. Most PTSD studies until now have used only male rats. Mount Sinai researchers included female rats in this study since women are more vulnerable than men to developing PTSD. The rats were then categorized based on their behavior one week after exposure to the scent. The authors also examined patterns of gene expression in the blood and in stress-responsive brain regions.
After one week of being exposed to soiled cat litter for 10 minutes, vulnerable rats exhibited higher anxiety and hyperarousal, and showed altered glucocorticoid receptor signaling in all tissues compared with resilient rats. Moreover, some rats were treated with a hormone that activates the glucocorticoid receptor called corticosterone one hour after exposure to the cat urine scent. These rats showed lower levels of anxiety and arousal one week later compared with untreated, trauma-exposed rats.
“PTSD is not just a disorder that affects the brain,” said co-investigator Nikolaos Daskalakis, MD, PhD, Associate Research Scientist in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai. “It involves the entire body, which is why identifying common regulators is key. The glucocorticoid receptor is the one common regulator that consistently stood out.”
(Image: photos.com)
Neurons at work
Film editors play a critical role by helping shape raw footage into a narrative. Part of the challenge is that their work can have a profound impact on the finished product — with just a few cuts in the wrong places, comedy can become tragedy, or vice versa.
A similar process, “alternative splicing,” is at work inside the bodies of billions of creatures — including humans. Just as a film editor can change the story with a few cuts, alternative splicing allows cells to stitch genetic information into different formations, enabling a single gene to produce up to thousands of different proteins.
Harvard scientists say they’ve now been able to observe that process within the nervous system of a living creature.
Overhaul of our understanding of why autism potentially occurs
An analysis of autism research covering genetics, brain imaging, and cognition led by Laurent Mottron of the University of Montreal has overhauled our understanding of why autism potentially occurs, develops and results in a diversity of symptoms. The team of senior academics involved in the project calls it the “Trigger-Threshold-Target” model. Brain plasticity refers to the brain’s ability to respond and remodel itself, and this model is based on the idea that autism is a genetically induced plastic reaction. The trigger is multiple brain plasticity-enhancing genetic mutations that may or may not combine with a lowered genetic threshold for brain plasticity to produce either intellectual disability alone, autism, or autism without intellectual disability. The model confirms that the autistic brain develops with enhanced processing of certain types of information, which results in the brain searching for materials that possess the qualities it prefers and neglecting materials that don’t. “One of the consequences of our new model will be to focus early childhood intervention on developing the particular strengths of the child’s brain, rather than exclusively trying to correct missing behaviors, a practice that may be a waste of a once in a lifetime opportunity,” Mottron said.
Mottron and his colleagues developed the model by examining the effect of mutations involved in autism together with the brain activity of autistic people as they undertake perceptual tasks. “Geneticists, using animals implanted with the mutations involved in autism, have found that most of them enhance synaptic plasticity – the capacity of brain cells to create connections when new information is encountered. In parallel, our group and others have established that autism represents an altered balance between the processing of social and non-social information, i.e. the interest, performance and brain activity, in favor of non-social information,” Mottron explained. “The Trigger-Threshold-Target model builds a bridge between these two series of facts, using the neuro cognitive effects of sensory deprivation to resolve the missing link between them.”
The various superiorities that subgroups of autistic people present in perception or in language indicates that an autistic infant’s brain adapts to the information it is given in a strikingly similar way to sensory-deprived people. A blind infant’s brain compensate the lack of visual input by developing enhanced auditory processing abilities for example, and a deaf infant readapts to process visual inputs in a more refined fashion. Similarly, cognitive and brain imaging studies of autistic people work reveal enhanced activity, connectivity and structural modifications in the perceptive areas of the brain. Differences in the domain of information “targeted” by these plastic processes are associated with the particular pattern of strengths and weaknesses of each autistic individual. “Speech and social impairment in some autistic toddlers may not be the result of a primary brain dysfunction of the mechanisms related to these abilities, but the result of their early neglect,” Mottron said. “Our model suggests that the autistic superior perceptual processing compete with speech learning because neural resources are oriented towards the perceptual dimensions of language, neglecting its linguistic dimensions. Alternatively, for other subgroups of autistic people, known as Asperger, it’s speech that’s overdeveloped. In both cases, the overdeveloped function outcompetes social cognition for brain resources, resulting in a late development of social skills.”
The model provides insight into the presence or absence of intellectual disability, which when causative mutation alter the function of brain cell networking. Rather than simply triggering a normal but enhanced plastic reaction, these mutations cause neurons to connect in a way that does not exist in non-autistic people. When brain cell networking functions normally, only the allocation of brain resources is changed.
As is the case with all children, environment and stimulation have an effect on the development and organization of an autistic child’s brain. “Most early intervention programs adopt a restorative approach by working on aspects like social interest. However this focus may monopolize resources in favor of material that the child process with more difficulties, Mottron said. “We believe that early intervention for autistic children should take inspiration from the experience of congenitally deaf children, whose early exposure to sign language has a hugely positive effect on their language abilities. Interventions should therefore focus on identifying and harnessing the autistic child’s strengths, like written language.” By indicating that autistic ‘’restricted interests” result from cerebral plasticity, this model suggest that they have an adaptive value and should therefore be the focus of intervention strategies for autism.
(Source: nouvelles.umontreal.ca)
New Study Points to a Brain Region Key to Contextual Memories
Dartmouth researchers demonstrate in a new study that a previously understudied part of the brain, the retrosplenial cortex, is essential for forming the basis for contextual memories, which help you to recall events ranging from global disasters to where you parked your car.
An important aspect of memory is the ability to recall the physical place, or context, in which an event occurred. For example, in recalling emotionally charged events such as the September 11 terror attacks or the assassination of President John F. Kennedy, we remember not only the event but also where we were when it happened. Indeed, in discussing such events with others, we often ask, “Where were you when … ?” Processing “where” information is also important for mundane events such as remembering where you parked your car.
Although it is known that a specific network of brain regions is important for contextual memory, it has not been known how different parts of the network contribute to this process. But using a newly developed technology known as “chemogenetics,” Professor David Bucci’s laboratory is beginning to show how different brain structures contribute to contextual learning and memory. Developed at the University of North Carolina School of Medicine, the chemogenetics technique enables researchers to “remotely control” the activity of brains cells. This is accomplished by using a virus to transfers genes for a synthetic receptor into a brain region. The receptors are responsive only to a synthetic drug that is administered through a simple injection. By binding to the receptors, the drug temporarily turns off—or on—brain cells in that region for a short amount of time.
Using this approach, Bucci’s laboratory demonstrated in an experiment with rats that the retrosplenial cortex is critical for forming the basis for contextual memories. It was the first time the chemogenetics technique had been used to turn off cells along the entire retrosplenial cortex. The importance of this finding is underscored by two recent studies showing that the hippocampus, another key brain region involved in contextual memories, is not itself active or necessary for forming the initial associations that underlie contextual memory.
The National Science Foundation recently awarded Bucci a five-year, $725,000 grant to continue this research.
“By providing new insight into the function of this part of the brain, our work will also have implications for understanding the basis for illnesses that impact contextual memory, such as Alzheimer’s disease,” Bucci says. “In fact, recent studies have shown that the retrosplenial cortex is one of the first brain areas that is damaged in persons with Alzheimer’s disease.”
The findings appear in The Journal of Neuroscience.
(Source: now.dartmouth.edu)
Treating Mental Illness by Changing Memories of Things Past
In the novel À larecherche du temps perdu (translated into English as Remembrance of Things Past), Marcel Proust makes a compelling case that our identities and decisions are shaped in profound and ongoing ways by our memories.
This truth is powerfully reflected in mental illnesses,like post traumatic stress disorder (PTSD) and addictions. In PTSD, memories of traumas intrude vividly upon consciousness, causing distress, driving people to avoid reminders of their traumas, and increasing risk for addiction and suicide. In addiction, memories of drug use influence reactions to drug-related cues and motivate compulsive drug use.
What if one could change these dysfunctional memories? Although we all like to believe that our memories are reliable and permanent, it turns out that memories may indeed be plastic.
The process for modifying memories, depicted in the graphic, is called memory reconsolidation. After memories are formed and stored, subsequent retrieval may make them unstable. In other words, when a memory is activated, it also becomes open to revision and reconsolidation in a new form.
"Memory reconsolidation is probably among the most exciting phenomena in cognitive neuroscience today. It assumes that memories may be modified once they are retrieved which may give us the great opportunity to change seemingly robust, unwanted memories," explains Dr. Lars Schwabe of Ruhr-University Bochum in Germany. He and his colleagues have authored a review paper on the topic, published in the current issue of Biological Psychiatry.
The idea of memory reconsolidation was initially discovered and demonstrated in rodents.
The first evidence of reconsolidation in humans was reported in a study in 2003, and the findings have since continued to accumulate. The current report summarizes the most recent findings on memory reconsolidation in humans and poses additional questions that must be answered by future studies.
"Reconsolidation appears to be a fundamental process underlying cognitive and behavioral therapies. Identifying its roles and mechanisms is an important step forward to fully harnessing the reconsolidation process in psychotherapy," said Dr. John Krystal, Editor of Biological Psychiatry.
The translation of the animal data to humans is a vital step for the potential application of memory reconsolidation in the context of mental disorders. Memory reconsolidation could open the door to novel treatment approaches for disorders such as PTSD or drug addiction.