Posts Tagged ‘neuroscience’

by CHRISTIAN COTRONEO

The mind may seem to thrive on stimuli — the honking horns, the pixels percolating on this screen at this very moment, or even the way the keyboard feels under your fingers at any given time of day.

But, in fact, it may be what lies between — the time between honks, if you will — when the brain focuses on encoding the information, according to a new study from Neuroscience Research Australia (NeuRA) and the University of New South Wales.

Of course, we’ve long known that silence is golden — especially when it comes to mental health and dealing with stress. But the new research points to the absence of stimulation as a window when the brain has a chance to learn from its environment.

Think of it as a micro-breather for the mind, allowing it to grasp and distill what it’s experiencing.

To reach that conclusion, researchers Ingvars Birznieks and Richard Vickery developed a unique way to control the neural information that’s presented to the brain. Essentially, they delivered short mechanical taps to the fingertips of study subjects.

Birznieks and Vickery ensured that each tap generated a corresponding nerve impulse to a neuron in the brain. By triggering the sense of touch — which the brain registers from vibrations along the ridge of our fingertips — the scientists were able to monitor how nerve impulses encoded the information.

The thing is, the frequency of those neuron bursts didn’t match the frequency of taps.

“Instead, it was the silent period between bursts that best explained the subjects’ experiences,” Birznieks noted in the NeuRA blog.

Prevailing theories had it that every vibration or tap would have a corresponding nerve impulse, or the brain would be able to detect a periodic regularity in the impulse patterns.

“We were hoping to disprove one of the two competing theories, but showing they were both incorrect and finding a completely new coding strategy totally surprised us,” Birznieks added.

The brain just kept ticking along to its own beat, independent of how often those fingertips were stimulated.

For neuroscience, the findings could be a game-changer. A better understanding of how the brain fields daily neural impulses could pave the way for more efficient interfaces between brain and machine.

And for the rest of us, it suggests that in a increasingly noise-addled society — where every sense seems in danger of over-stimulation — it may do a body good to give the brain a breather.

https://www.mnn.com/green-tech/research-innovations/stories/silence-brain-study-touch-stimulation

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Fresh or frozen human blood samples can be directly transformed into patient-specific neurons to study disorders such as schizophrenia and autism, Stanford researcher Marius Wernig has found.

Human immune cells in blood can be converted directly into functional neurons in the laboratory in about three weeks with the addition of just four proteins, researchers at the Stanford University School of Medicine have found.

The dramatic transformation does not require the cells to first enter a state called pluripotency but instead occurs through a more direct process called transdifferentiation.

The conversion occurs with relatively high efficiency — generating as many as 50,000 neurons from 1 milliliter of blood — and it can be achieved with fresh or previously frozen and stored blood samples, which vastly enhances opportunities for the study of neurological disorders such as schizophrenia and autism.

“Blood is one of the easiest biological samples to obtain,” said Marius Wernig, MD, associate professor of pathology and a member of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “Nearly every patient who walks into a hospital leaves a blood sample, and often these samples are frozen and stored for future study. This technique is a breakthrough that opens the possibility to learn about complex disease processes by studying large numbers of patients.”

A paper describing the findings was published online June 4 in the Proceedings of the National Academy of Sciences. Wernig is the senior author. Former postdoctoral scholar Koji Tanabe, PhD, and graduate student Cheen Ang are the lead authors.

Dogged by challenges

The transdifferentiation technique was first developed in Wernig’s laboratory in 2010 when he and his colleagues showed that they could convert mouse skin cells into mouse neurons without first inducing the cells to become pluripotent — a developmentally flexible stage from which the cells can become nearly any type of tissue. They went on to show the technique could also be used on human skin and liver cells.

But each approach has been dogged by challenges, particularly for researchers wishing to study genetically complex mental disorders, such as autism or schizophrenia, for which many hundreds of individual, patient-specific samples are needed in order to suss out the relative contributions of dozens or more disease-associated mutations.

“Generating induced pluripotent stem cells from large numbers of patients is expensive and laborious. Moreover, obtaining skin cells involves an invasive and painful procedure,” Wernig said. “The prospect of generating iPS cells from hundreds of patients is daunting and would require automation of the complex reprogramming process.”

Although it’s possible to directly convert skin cells to neurons, the biopsied skin cells first have to be grown in the laboratory for a period of time until their numbers increase — a process likely to introduce genetic mutations not found in the person from whom the cells were obtained.

The researchers wondered if there was an easier, more efficient way to generate patient-specific neurons.

‘Somewhat mind-boggling’
In the new study, Wernig and his colleague focused on highly specialized immune cells called T cells that circulate in the blood. T cells protect us from disease by recognizing and killing infected or cancerous cells. In contrast, neurons are long and skinny cells capable of conducting electrical impulses along their length and passing them from cell to cell. But despite the cells’ vastly different shapes, locations and biological missions, the researchers found it unexpectedly easy to complete their quest.

“It’s kind of shocking how simple it is to convert T cells into functional neurons in just a few days,” Wernig said. “T cells are very specialized immune cells with a simple round shape, so the rapid transformation is somewhat mind-boggling.”

The resulting human neurons aren’t perfect. They lack the ability to form mature synapses, or connections, with one another. But they are able to carry out the main fundamental functions of neurons, and Wernig and his colleague are hopeful they will be able to further optimize the technique in the future. In the meantime, they’ve started to collect blood samples from children with autism.

“We now have a way to directly study the neuronal function of, in principle, hundreds of people with schizophrenia and autism,” Wernig said. “For decades we’ve had very few clues about the origins of these disorders or how to treat them. Now we can start to answer so many questions.”

Other Stanford co-authors are postdoctoral scholars Soham Chanda, PhD, and Daniel Haag, PhD; undergraduate student Victor Olmos; professor of psychiatry and behavioral sciences Douglas Levinson, MD; and professor of molecular and cellular physiology Thomas Südhof, MD.

The research was supported by the National Institutes of Health (grants MH092931 and MH104172), the California Institute for Regenerative Medicine, the New York Stem Cell Foundation, the Howard Hughes Medical Institute, the Siebel Foundation and the Stanford Schizophrenia Genetics Research Fund.

http://med.stanford.edu/news/all-news/2018/06/human-blood-cells-transformed-into-functional-neurons.html

The majority of the cells in the brain are no neurons, but Glia (from “glue”) cells, that support the structure and function of the brain. Astrocytes (“start cells”) are star-shaped glial cells providing many supportive functions for the neurons surrounding them, such as the provision of nutrients and the regulation of their chemical environment. Newer studies showed that astrocytes also monitor and modulate neuronal activity. For example, these studies have shown that astrocytes are necessary for the ability of neurons to change the strength of the connections between them, the process underlying learning and memory, and indeed astrocytes are also necessary for normal cognitive function. However, it is still unknown whether astrocytic activity is only necessary, or is it may also be sufficient to induce synaptic potentiation and enhance cognitive performance.

In a new study published in Cell, two graduate students, Adar Adamsky and Adi Kol, from Inbal Goshen’s lab, employed chemogenetic and optogenetic tools that allow specific activation of astrocytes in behaving mice, to explore their role in synaptic activity and memory performance. They found that astrocytic activation in the hippocampus, a brain region that plays an important role in memory acquisition and consolidation, potentiated the synaptic connections in this region, measured in brain slices. Moreover, in the intact brain, astrocytic activation enhanced hippocampal neuronal activity in a task-dependent way: i.e. only during when it was combined with memory acquisition, but not when mice were at their home cage with no meaningful stimuli. The ability of astrocytes to increase neuronal activity during memory acquisition had a significant effect on cognitive function: Specifically, astrocytic activation during learning resulted in enhanced memory in two memory tests. In contrast, direct neuronal activation in the hippocampus induced a non-selective increase in activity (during learning or in the home cage), and thus resulted in drastic memory impairment.

The results suggest that the memory enhancement induced by astrocytic activation during learning is not simply a result of a general increase in hippocampal neuronal activity. Rather, the astrocytes, which sense and respond to changes in the surrounding neuronal activity, can detect and specifically enhance only the neuronal activity involved in learning, without affecting the general activity. This may explain why general astrocytic activation improves memory performance, whereas a similar activation of neurons impairs it.

Memory is not a binary process (remember/don’t remember); the strength of a memory can vary greatly, either for the same memory or between different memories. Here, we show that activating astrocytes in mice with intact cognition improves their memory performance. This finding has important clinical implications for cognitive augmentation treatments. Furthermore, the ability of astrocytes to strengthen neuronal communication and improve memory performance supports the claim that astrocytes are able to take an active part in the neuronal processes underlying cognitive function. This perspective expands the definition of the role of astrocytes, from passive support cells to active cells that can modulate neural activity and thus shape behavior.

Link: https://www.cell.com/cell/pdf/S0092-8674(18)30575-0.pdf

https://elsc.huji.ac.il/content/article-month-june-2018-goshens-lab


Signals long thought to be “noise” appear to represent a distinct form of brain activity.

By Tanya Lewis

Every few seconds a wave of electrical activity travels through the brain, like a large swell moving through the ocean. Scientists first detected these ultraslow undulations decades ago in functional magnetic resonance imaging (fMRI) scans of people and other animals at rest—but the phenomenon was thought to be either electrical “noise” or the sum of much faster brain signals and was largely ignored.

Now a study that measured these “infraslow” (less than 0.1 hertz) brain waves in mice suggests they are a distinct type of brain activity that depends on an animal’s conscious state. But big questions remain about these waves’ origin and function.

An fMRI scan detects changes in blood flow that are assumed to be linked to neural activity. “When you put someone in a scanner, if you just look at the signal when you don’t ask the subject to do anything, it looks pretty noisy,” says Marcus Raichle, a professor of radiology and neurology at Washington University School of Medicine in St. Louis and senior author of the new study, published in April in Neuron. “All this resting-state activity brought to the forefront: What is this fMRI signal all about?”

To find out what was going on in the brain, Raichle’s team employed a combination of calcium/hemoglobin imaging, which uses fluorescent molecules to detect the activity of neurons at the cellular level, and electrophysiology, which can record signals from cells in different brain layers. They performed both measurements in awake and anesthetized mice; the awake mice were resting in tiny hammocks in a dark room.

The team found that infraslow waves traveled through the cortical layers of the awake rodents’ brains—and changed direction when the animals were anesthetized. The researchers say these waves are distinct from so-called delta waves (between 1 and 4 Hz) and other higher-frequency brain activity.

These superslow waves may be critical to how the brain functions, Raichle says. “Think of, say, waves on the water of Puget Sound. You can have very rough days where you have these big groundswells and then have whitecaps sitting on top of them,” he says. These “swells” make it easier for brain areas to become active—for “whitecaps” to form, in other words.

Other researchers praised the study’s general approach but were skeptical that it shows the infraslow waves are totally distinct from other brain activity. “I would caution against jumping to a conclusion that resting-state fMRI is measuring some other property of the brain that’s got nothing to do with the higher-frequency fluctuations between areas of the cortex,” says Elizabeth Hillman, a professor of biomedical engineering at Columbia University’s Zuckerman Institute, who was not involved in the work. Hillman published a study in 2016 finding that resting-state fMRI signals represent neural activity across a range of frequencies, not just low ones.

More studies are needed to tease apart how these different types of brain signals are related. “These kinds of patterns are very new,” Hillman notes. “We haven’t got much of a clue what they are, and figuring out what they are is really, really difficult.”

https://www.scientificamerican.com/article/superslow-brain-waves-may-play-a-critical-role-in-consciousness1/


by Nicolas Scherger

Dr. Thomas Hainmüller and Prof. Dr. Marlene Bartos of the Institute of Physiology of the University of Freiburg have established a new model to explain how the brain stores memories of tangible events. The model is based on an experiment that involved mice seeking a place where they received rewards in a virtual environment. The scientific journal “Nature” has published the study.

In the world of the mouse’s video game, the walls that depict a corridor four meters long are made up of green and blue patterned blocks. The floor is marked with turquoise dots. A short distance away, there’s a brown disc on the floor that looks like a cookie. That’s the symbol for the reward location. The mouse heads for it, gets there, and the symbol disappears. The next cookie promptly appears a bit further down the corridor. The mouse is surrounded by monitors and is standing on a styrofoam ball that is floating on compressed air and turns beneath the mouse when it runs. The ball makes it possible to transfer of the mouse’s movements to the virtual environment. If the mouse reaches the reward symbol, a straw is used to give it a drop of soy milk and stimulate it to form memories of its experiences in the virtual world. The mouse learns when, and at which location, it will receive a reward. It also learns how to locate itself and discriminate between different corridors in the video game.

Viewing the brain with a special microscope

“As the mouse is getting to know its environment, we use a special microscope to look from the outside into its brain and we record the activities of its nerve cells on video,” explains Thomas Hainmüller, a physician and doctoral candidate in the MD/PhD program of the Spemann Graduate School of Biology and Medicine (SGBM) of the University of Freiburg. He says that works because, in reality, the head of the mouse remains relatively still under the microscope as it runs through the virtual world of the video game. On the recordings, the mice’s genetically-manipulated nerve cells flash as soon as they become active. Hainmüller and Marlene Bartos, a Professor of Systemic and Cellular Neurobiology are using this method to investigate how memories are sorted and retrieved. “We repeatedly place the mouse in the virtual world on consecutive days,” says Hainmüller. “In that way, we can observe and compare the activity of the nerve cells in different stages of memory formation,” he explains.

Nerve cells encode places

The region of the brain called the hippocampus plays a decisive role in the formation of memory episodes – or memories of tangible experiences. Hainmüller and Bartos published that the nerve cells in the hippocampus create a map of the virtual world in which single neurons code for actual places in the video game. Earlier studies done at the Freiburg University Medical Center showed that nerve cells in the human hippocampus code video games in the same way. The cells become activated and flash when the mouse is at the respective place, otherwise they remain dark. “To our surprise, we found very different maps inside the hippocampus,” reports Hainmüller. In part, they provide an approximate overview of the position of the mouse in the corridor, yet they also consider time and context factors, and above all, information about in which of the corridors the mouse is located. The maps are also updated during the days of the experiment and as a result can be recognized as a learning process.

Better understanding of memory formation

The research team summarizes, saying that their observations provide a model that explains how activity of the nerve cells in the hippocampus can map the space, time and and context of memory episodes. The findings allow for better understanding of the biological processes that effect the formation of memory in the brain. Hainmüller says, “In the long term, we would like to use our results to contribute to the development of treatments to help people with neurological and psychiatric illnesses.”

Original publication
Thomas Hainmüller and Marlene Bartos (2018): Parallel emergence of stable and dynamic memory engrams in the hippocampus. In: Nature. doi: 10.1038/s41586-018-0191-2

https://www.pr.uni-freiburg.de/pm-en/online-magazine/research-and-discover/maps-made-of-nerve-cells

By Hilary Hurd Anyaso

Leading theories propose that sleep presents an opportune time for important, new memories to become stabilized. And it’s long been known which brain waves are produced during sleep. But in a new study, researchers set out to better understand the brain mechanisms that secure memory storage.

The team from Northwestern and Princeton universities set out to find more direct and precisely timed evidence for the involvement of one particular sleep wave — known as the “sleep spindle.”

In the study, sleep spindles, described as bursts of brain activity typically lasting around one second, were linked to memory reactivation. The paper, “Sleep spindle refractoriness segregates periods of memory reactivation,” published today in the journal Current Biology.

“The most novel aspect of our study is that we found these spindles occur rhythmically — about every three to six seconds — and this rhythm is related to memory,” said James W. Antony, first author of the study and a postdoctoral fellow in Princeton’s Computational Memory Lab.

Three experiments explored how recent memories are reactivated during sleep. While volunteers took an afternoon nap, sound cues were surreptitiously played. Each was linked to a specific memory. The researchers’ final experiment showed that if cues were presented at opportune times such that spindles could follow them, the linked memories were more likely to be retained. If they were presented when a spindle was unlikely to follow, the linked memories were more likely to be forgotten.

“One particularly remarkable aspect of the study was that we were able to monitor spindles moment by moment while people slept,” said Ken A. Paller, senior author of the study and professor of psychology at Northwestern’s Weinberg College of Arts and Sciences. “Therefore, we could know when the brain was most ready for us to prompt memory reactivation.”
If the researchers reminded people of a recently learned fact, a spindle would likely be evident in the cerebral cortex, and memory for that information would be improved, added Paller, also director of Northwestern’s Cognitive Neuroscience Program.

“In memory research, we know it’s important to segregate experiences while you’re awake so that everything doesn’t just blend together,” said Antony, who worked in Paller’s lab at Northwestern as a doctoral student. “If that happens, you may have difficulty retrieving information because so many things will come to mind at once. We believe the spindle rhythmicity shown here might play a role in segregating successive memory reactivations from each other, preventing overlap that might cause later interference between memories.”

Ultimately, the researchers’ goal is to understand how sleep affects memory under natural conditions and how aging or disease can impact these functions.

“With that goal in mind, we’ve helped elucidate the importance of sleep spindles more generally,” Antony said.

Paller said they are on the trail of the physiology of memory reactivation.

“Future work will be needed to see how spindles fit together with other aspects of the physiology of memory and will involve other types of memory testing and other species,” Paller said.

In addition to Antony and Paller, co-authors are Luis Piloto, Margaret Wang, Paula Pacheco and Kenneth A. Norman, all of Princeton.

https://news.northwestern.edu/stories/2018/may/bursts-of-brain-activity-linked-to-memory-reactivation/

By Rachael Rettner

Many people tend to look back on the past with rose-colored glasses, remembering the good times and the good feelings…while forgetting the bad.

But a new study suggests that heavy marijuana users may have some trouble letting go of negative emotions tied to memories — a phenomenon that’s also seen in people with depression. Earlier research has also linked marijuana use with depression.

Although the new results are very preliminary, the findings, presented here on Friday (May 25) at the annual meeting of the Association for Psychological Science, may offer clues about the link between marijuana use and depression.

Rose-colored memories

The study explored a psychological phenomenon called “fading affect bias,” in which people tend to hold on to positive feelings tied to their memories more than they hold on to negative feelings. In other words, negative feelings related to our memories fade faster than positive ones.

Psychologists have hypothesized that this phenomenon, which is generally seen in people without mental health conditions, may serve as a sort of “psychological immune system,” said study lead author Daniel Pillersdorf, a graduate student in psychology at the University of Windsor in Ontario. This may be “so that we think more pleasantly in general, and don’t have that cognitive burden of holding on to negative emotions associated with memories,” Pillersdorf said.

Some previous studies have suggested that this fading affect bias may be different for people who use drugs, but no studies have looked at whether marijuana use could affect this phenomenon.

In the new study, the researchers analyzed information from 46 heavy marijuana users — most of whom used the drug at least four times a week — and 51 people who didn’t use marijuana. Participants were asked to recall, and provide written descriptions of, three pleasant memories and three unpleasant memories from the past year. The participants were then asked to rate the intensity of emotion tied to those memories, on a scale of negative 10, meaning extremely unpleasant, to positive 10, or extremely pleasant. They rated their emotions both at the time the memory was made, and at the current time. (Marijuana users were not under the influence at the time the researchers asked them the questions.)

The researchers found that both marijuana users and non-users showed fading affect bias, but for marijuana users, the fading was a lot less.

“They were hanging on to that unpleasant affect over time, much more” than non-users, Pillersdorf told Live Science. “They were less able … to shed that unpleasantness associated with their memories.”

The study also found that marijuana users tended to recall life events in more general terms than specific ones. For example, when asked about a happy event in the past year, marijuana users were more likely to respond with general or broad answers such as “I went on vacation,” rather than recalling a specific event or day, such as “I attended my college graduation.” This phenomenon is known as over-general autobiographical memory, and it’s also linked with depression, Pillersdorf said.

It’s important to note that the new study found only an association and cannot determine why marijuana users show less fading affect bias, and more overgeneral memory, than non-users.

Link with depression?

Even so, the new findings agree with previous research that has found a link between heavy marijuana use and depression. However, researchers don’t know why marijuana and depression are linked — it could be that marijuana use plays a role in developing depression, or that people who are already depressed are more likely to use the drug. [7 Ways Marijuana May Affect the Brain]

Based on the new findings, one hypothesis is that the decreased “fading” of negative memories in marijuana users could be contributing to the development or continuing of depression, Pillersdorf said. “It may be that, chronic or frequent cannabis use is putting [a person] more at risk for the development or continuing of depression,” he said. However, Pillersdorf stressed that this is just a hypothesis that would need to be investigated with future research.

To further investigate the link, researchers will need to study marijuana users and non-users over long periods of time. For example, researchers could start with people in their late teens or early 20s, who don’t have depression, and see if those who use marijuana frequently are more likely to eventually develop depression than non-users.

Additional studies could also investigate whether other substances have an effect on fading affect bias, Pillersdorf said.

The study has not yet been published in a peer-reviewed journal.

https://www.livescience.com/62679-marijuana-negative-memories.html?utm_source=notification