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Spatial and Sex-Dependent Responses of Adult Endogenous Neural Stem Cells to Alcohol Consumption: Stem Cell Reports

hronic alcohol abuse results in alcohol-related neurodegeneration, and critical gaps in our knowledge hinder therapeutic development. Neural stem cells (NSCs) are a subpopulation of cells within the adult brain that contribute to brain maintenance and recovery. While it is known that alcohol alters NSCs, little is known about how NSC response to alcohol is related to sex, brain region, and stage of differentiation. Understanding these relationships will aid in therapeutic development. Here, we used an inducible transgenic mouse model to track the stages of differentiation of adult endogenous NSCs and observed distinct NSC behaviors in three brain regions (subventricular zone, subgranular zone, and tanycyte layer) after long-term alcohol consumption. Particularly, chronic alcohol consumption profoundly affected the survival of NSCs in the subventricular zone and altered NSC differentiation in all three regions. Significant differences between male and female mice were further discovered.

Your brain does not process information and it is not a computer | Aeon Essays

Worse still, even if we had the ability to take a snapshot of all of the brain’s 86 billion neurons and then to simulate the state of those neurons in a computer, that vast pattern would mean nothing outside the body of the brain that produced it. This is perhaps the most egregious way in which the IP metaphor has distorted our thinking about human functioning. Whereas computers do store exact copies of data – copies that can persist unchanged for long periods of time, even if the power has been turned off – the brain maintains our intellect only as long as it remains alive. There is no on-off switch. Either the brain keeps functioning, or we disappear. What’s more, as the neurobiologist Steven Rose pointed out in The Future of the Brain (2005), a snapshot of the brain’s current state might also be meaningless unless we knew the entire life history of that brain’s owner – perhaps even about the social context in which he or she was raised.

'Multi-dimensional universe' in brain networks: Using mathematics in a novel way in neuroscience, scientists demonstrate that the brain operates on many dimensions, not just the 3 dimensions that we are accustomed to -- ScienceDaily

Using algebraic topology in a way that it has never been used before in neuroscience, a team from the Blue Brain Project has uncovered a universe of multi-dimensional geometrical structures and spaces within the networks of the brain. The research, published today in Frontiers in Computational Neuroscience, shows that these structures arise when a group of neurons forms a clique: each neuron connects to every other neuron in the group in a very specific way that generates a precise geometric object. The more neurons there are in a clique, the higher the dimension of the geometric object. "We found a world that we had never imagined," says neuroscientist Henry Markram, director of Blue Brain Project and professor at the EPFL in Lausanne, Switzerland, "there are tens of millions of these objects even in a small speck of the brain, up through seven dimensions. In some networks, we even found structures with up to eleven dimensions." Markram suggests this may explain why it has been so hard to understand the brain. "The mathematics usually applied to study networks cannot detect the high-dimensional structures and spaces that we now see clearly."

Diverse populations make rational collective decisions -- ScienceDaily

The team found that individual ants had different yet consistent preferences. Some of the ants were happy to feed on either of the two solutions. Picky ants refused to feed from either. A third "middle" group consistently chose the solution with a higher concentration. These varied choices demonstrated that individual ants had individual thresholds to the sucrose concentration and made yes/no binary decisions accordingly. The researchers then fed each colony again with the differing sucrose solutions and found that the majority of the ants in all six experimental colonies chose the 4.0% sucrose solution, without being influenced by other ants in the colony. The "collective" decision of the colony was thus for the more nourishing solution. "Importantly, neither ants with a low threshold and high threshold contributed to the collective decision making, since the former didn't care about the concentration and the latter refused both concentrations. Thus, the decision maker was the middle group which preferred the higher concentration," says Hasegawa. "The study demonstrates simple yes/no judgements by individuals can lead to a collective rational decision, without using quality-graded responses, when they have diverse thresholds in the population," he continued. This mechanism can be applied to various fields including brain science, behavioural science, swarm robotics and consensus decision-making in human societies, conclude the researchers.

What Is This Thing Called Consciousness?

Yet the cerebellum has everything you expect of neurons. It has gorgeous neurons. In fact, some of the most beautiful neurons in the brain, so-called Purkinje cells, are found in the cerebellum. Why does the cerebellum not contribute to consciousness? It has a very repetitive and monotonous circuitry. It has 69 billion neurons, but they have simple feed-forward loops. So I believe the way the cerebellum is wired up does not give rise to consciousness. Yet another part of the brain, the cerebral cortex, seems to be wired up in a much more complicated way. We know it’s really the cortex that gives rise to conscious experience.

Bipolar disorder: New method predicts who will respond to lithium therapy -- ScienceDaily

Wondering whether the differences could be predictive, the team trained a computer program to recognize the variations between the profiles of responders and nonresponders using the firing patterns of 450 total neurons over six independent training rounds. In each round, they started fresh with the neurons of five of the patients to train the system. They then tested the system with the neurons of the sixth patient, whose lithium status was known to the team but not to the program. They repeated the process five more times, which allowed them to build essentially six independent models. Each model was trained on the data from five out of the six patients, leaving a different patient out of the training data each time, and then letting the model classify this remaining patient as a responder or nonresponder. Using the firing patterns of just five of any patient's neurons, the system identified the person as a responder or nonresponder with 92 percent accuracy.

Mouse study identifies new method for treating depression: Inhibiting brain enzyme alleviates depression, and does it much faster than conventional antidepressants -- ScienceDaily

Palmer and team unraveled a previously underappreciated molecular process that can influence mouse models of depression. Here's how the process works: Cells generate energy. In doing so, they produce a byproduct. That byproduct inhibits neurons and thus influences various behaviors. Typically, the enzyme GLO1 removes this byproduct, but inhibiting GLO1 can also increase the activity of certain neurons in a beneficial way. In mice, Palmer and others have shown that more GLO1 activity makes mice more anxious, but less was known about the system's effect on depression. Palmer and team wondered if they could reduce signs of depression by inhibiting the GLO1 enzyme. The researchers used several different antidepressant tests. They compared responses in three groups of mice: 1) untreated, 2) treated by inhibiting GLO1, either genetically or with an experimental compound, and 3) treated with Prozac, a selective serotonin reuptake inhibitor commonly used to treat depression. The first tests they used were the tail suspension test and the forced swim tests, which are often used to determine whether or not a compound is an antidepressant. In this case, the answer was yes. The other tests -- chronic forced swim test, chronic mild stress paradigm and olfactory bulbectomy -- are well-established measures that can also be used to measure how long it takes for an antidepressant to take effect. In each of these tests, inhibiting the GLO1 enzyme reduced depression-like symptoms in five days, whereas it took 14 days for Prozac to have the same effect. While this new approach to treating depression has so far only been tested in mice and it will take many years of development before a GLO1 inhibitor could be tested in humans, the researchers are excited to find that new, unexplored approaches to treating depression are out there.

Dopamine toggling governs decision making

The voltammetry results showed that fluctuations in brain dopamine level were tightly associated with the animal's decision. The scientists were actually able to accurately predict the animal's upcoming choice of lever based on dopamine concentration alone. Interestingly, other mice that got a treat by pressing either lever (so removing the element of choice) experienced a dopamine increase as trials got under way, but in contrast their levels remained above baseline (didn't fluctuate below baseline) the entire time, indicating dopamine's evolving role when a choice is involved. "We are very excited by these findings because they indicate that dopamine could also be involved in ongoing decision, beyond its well-known role in learning," adds the paper's co-first author, Christopher Howard, a Salk research collaborator. To verify that dopamine level caused the choice change, rather than just being associated with it, the team used genetic engineering and molecular tools -- including activating or inhibiting neurons with light in a technique called optogenetics -- to manipulate the animals' brain dopamine levels in real time. They found they were able to bidirectionally switch mice from one choice of lever to the other by increasing or decreasing dopamine levels. Jin says these results suggest that dynamically changing dopamine levels are associated with the ongoing selection of actions. "We think that if we could restore the appropriate dopamine dynamics -- in Parkinson's disease, OCD and drug addiction -- people might have better control of their behavior. This is an important step in understanding how to accomplish that."

How the brain maintains useful memories -- ScienceDaily

there are specific groups of neurons in the medial prefrontal cortex (mPFC) of a rat's brain -- the region most associated with long-term memory. These neurons develop codes to help store relevant, general information from multiple experiences while, over time, losing the more irrelevant, minor details unique to each experience. The findings provide new insight into how the brain collects and stores useful knowledge about the world that can be adapted and applied to new experiences. "Memories of recent experiences are rich in incidental detail but, with time, the brain is thought to extract important information that is common across various past experiences," says Kaori Takehara-Nishiuchi, senior author and Associate Professor of Psychology at the University of Toronto. "We predicted that groups of neurons in the mPFC build representations of this information over the period when long-term memory consolidation is known to take place, and that this information has a larger representation in the brain than the smaller details."

The Serotonin Surprise | DiscoverMagazine.com

Glenmullen has long suspected that drugs that alter serotonin metabolism cause profound changes in the brain. He bases his suspicion on a body of research during the last 20 years by scientists investigating another class of drugs that includes MDMA (Ecstasy) as well as fenfluramine, the diet drug recently removed from the market because of its association with heart valve problems. These drugs do more than just block serotonin reuptake; they primarily stimulate the release of large quantities of serotonin from nerve endings into the brain. The resulting flood is thought to cause the mind-altering effects of MDMA. And that flood, some scientists argue, leaves brain damage in its wake. When monkeys and rats are given high doses of serotonin releasers--up to 40 times the dose that people generally take--the microscopic architecture of their brains looks different from normal brains. The nerve fibers (axons) that carry serotonin to the target cells seem to change their shape and diminish in number--effects some scientists claim are properly understood as brain damage.

How aerobic exercise enhances neuroplasticity in the brain

A brief but intense period of aerobic exercise immediately reduces GABA, the main inhibitory neurotransmitter in the brain. GABA play an important role in regulating the brain’s capacity to undergo change or neuroplasticity. We observed reduced excitability of GABA-mediated networks in the motor cortex, which may explain findings from previous studies where enhanced neuroplasticity is observed after aerobic exercise. Our findings may have implications for individuals after stroke, where GABA is a promising target for promoting neuroplasticity to promote recovery of motor function.

Synapses shrink 20% every night?!

The team deliberately did not know whether they were analyzing the brain cells of a well-rested mouse or one that had been awake. When they finally "broke the code" and correlated the measurements with the amount of sleep the mice had during the six to eight hours before the image was taken, they found that a few hours of sleep led on average to an 18 percent decrease in the size of the synapses. These changes occurred in both areas of the cerebral cortex and were proportional to the size of the synapses. The scaling occurred in about 80 percent of the synapses but spared the largest ones, which may be associated with the most stable memory traces.

Talking therapy changes the brain's wiring, study reveals for first time -- ScienceDaily

CBT -- a specific type of talking therapy -- involves people changing the way they think about and respond to their thoughts and experiences. For individuals experiencing psychotic symptoms, common in schizophrenia and a number of other psychiatric disorders, the therapy involves learning to think differently about unusual experiences, such as distressing beliefs that others are out to get them. CBT also involves developing strategies to reduce distress and improve wellbeing. The findings, published in the journal Translational Psychiatry, follow the same researchers' previous work which showed that people with psychosis who received CBT displayed strengthened connections between key regions of the brain involved in processing social threat accurately. The new results show for the first time that these changes continue to have an impact years later on people's long-term recovery.

Cardiovascular fitness, cortical plasticity, and aging. - PubMed - NCBI

Cardiovascular fitness is thought to offset declines in cognitive performance, but little is known about the cortical mechanisms that underlie these changes in humans. Research using animal models shows that aerobic training increases cortical capillary supplies, the number of synaptic connections, and the development of new neurons. The end result is a brain that is more efficient, plastic, and adaptive, which translates into better performance in aging animals. Here, in two separate experiments, we demonstrate for the first time to our knowledge, in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task. Specifically, highly fit (Study 1) or aerobically trained (Study 2) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning, when compared with low-fit (Study 1) or nonaerobic control (Study 2) participants. Additionally, in both studies there exist groupwise differences in activation of the anterior cingulate cortex, which is thought to monitor for conflict in the attentional system, and signal the need for adaptation in the attentional network. These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain, and may serve to reduce both biological and cognitive senescence in humans.

Capitalizing on cortical plasticity: influence of physical activity on cognition and brain function. - PubMed - NCBI

In this review, we evaluate the hypothesis that physical activity and exercise might serve to protect, and also enhance, cognitive and brain function across the adult lifespan.

Running + challenges lead to neurogenisis

Voluntary physical exercise (wheel running, RUN) and environmental enrichment both stimulate adult hippocampal neurogenesis but do so by different mechanisms. RUN induces precursor cell proliferation, whereas ENR exerts a survival-promoting effect on newborn cells. In addition, continued RUN prevented the physiologically occurring age-related decline in precursor cell in the dentate gyrus but did not lead to a corresponding increase in net neurogenesis. We hypothesized that in the absence of appropriate cognitive stimuli the potential for neurogenesis could not be realized but that an increased potential by proliferating precursor cells due to RUN could actually lead to more adult neurogenesis if an appropriate survival-promoting stimulus follows the exercise. We thus asked whether a sequential combination of RUN and ENR (RUNENR) would show additive effects that are distinct from the application of either paradigm alone. We found that the effects of 10 days of RUN followed by 35 days of ENR were additive in that the combined stimulation yielded an approximately 30% greater increase in new neurons than either stimulus alone, which also increased neurogenesis.

Self-generated vision inputs suppressed

That's because the brain can tell if visual motion is self-generated, canceling out information that would otherwise make us feel -- and act -- as if the world was whirling around us. It's an astonishing bit of neural computation -- one that Maimon and his team are attempting to decode in fruit flies. And the results of their most recent investigations, published in Cell on January 5, provide fresh insights into how the brain processes visual information to control behavior. Each time you shift your gaze (and you do so several times a second), the brain sends a command to the eyes to move. But a copy of that command is issued internally to the brain's own visual system, as well. This allows the brain to predict that it is about to receive a flood of visual information resulting from the body's own movement -- and to compensate for it by suppressing or enhancing the activity of particular neurons.

Perceptually relevant remapping of human somatotopy in 24 hours. - PubMed - NCBI

Experience-dependent reorganisation of functional maps in the cerebral cortex is well described in the primary sensory cortices. However, there is relatively little evidence for such cortical reorganisation over the short-term. Using human somatosensory cortex as a model, we investigated the effects of a 24-hour gluing manipulation in which the right index and right middle fingers (digits 2 & 3) were adjoined with surgical glue. Somatotopic representations, assessed with two 7 tesla fMRI protocols, revealed rapid off-target reorganisation in the non-manipulated fingers following gluing, with the representation of the ring finger (digit 4) shifted towards the little finger (digit 5) and away from the middle finger (digit 3). These shifts were also evident in two behavioural tasks conducted in an independent cohort, showing reduced sensitivity for discriminating the temporal order of stimuli to the ring and little fingers, and increased substitution errors across this pair on a speeded reaction time task.

Runners' brains may be more connected, research shows | EurekAlert! Science News

University of Arizona researchers compared brain scans of young adult cross country runners to young adults who don't engage in regular physical activity. The runners, overall, showed greater functional connectivity -- or connections between distinct brain regions -- within several areas of the brain, including the frontal cortex, which is important for cognitive functions such as planning, decision-making and the ability to switch attention between tasks.

How hearing loss can change the way nerve cells are wired -- ScienceDaily

In mice whose ears were blocked, cells in the auditory nerve started to use their supplies of neurotransmitter more freely. They depleted their reserves of these chemicals rapidly each time a new auditory signal came in, and they decreased the amount of space within the cells that housed sac-like structures called vesicles -- biological storage tanks where neurotransmitter chemicals are kept. "When it's quiet, the demands on the auditory nerve cells are not as great," Xu-Friedman says. "So it makes sense that you would see these changes: You no longer need as much neurotransmitter, so why invest in a lot of storage? If you're not that active, you don't need a big gas tank. And you're not as afraid to use up what you have. This is one plausible explanation for what we observed." The changes in cellular structure and behavior were the opposite of what Xu-Friedman team's saw in a previous study that placed mice in a consistently noisy environment. In that project -- faced with an unusually high level of noise -- the mice's auditory nerve cells started to economize their resources, conserving supplies of neurotransmitter while increasing the storage capacity for the chemicals. "It looks like these effects are two sides of the same coin, and they might be the first hints of a general rule that nerve cells regulate their connections based on how active they are," Xu-Friedman says.

Substance present in ayahuasca brew stimulates generation of human neural cells: Harmine increases the number of neural progenitors, cells that give rise to neurons, study suggests -- ScienceDaily

In order to elucidate these effects, researchers from the D'Or Institute for Research and Education (IDOR) and the Institute of Biomedical Sciences at the Federal University of Rio de Janeiro (ICB-UFRJ) exposed human neural progenitors to this beta-carboline. After four days, harmine led to a 70% increase in proliferation of human neural progenitor cells. Researchers were also able to identify how the human neural cells respond to harmine. The described effect involves the inhibition of DYRK1A, which is located on chromosome 21 and is over activated in patients with Down syndrome and Alzheimer's Disease. "Our results demonstrate that harmine is able to generate new human neural cells, similarly to the effects of classical antidepressant drugs, which frequently are followed by diverse side effects. Moreover, the observation that harmine inhibits DYRK1A in neural cells allows us to speculate about future studies to test its potential therapeutic role over cognitive deficits observed in Down syndrome and neurodegenerative diseases," suggests Stevens Rehen, researcher from IDOR and ICB-UFRJ.

Portions of the brain fall asleep and wake back up all the time, Stanford researchers find | EurekAlert! Science News

The team used what amounts to sets of very sensitive pins that can record activity from a column of neurons in the brain. In the past, people had known that individual neurons go through phases of being more or less active, but with this probe they saw for the first time that all the neurons in a given column cycled together between firing very rapidly then firing at a much slower rate, similar to coordinated cycles in sleep. "During an on state the neurons all start firing rapidly," said Kwabena Boahen, a professor of bioengineering and electrical engineering at Stanford and a senior author on the paper. "Then all of a sudden they just switch to a low firing rate. This on and off switching is happening all the time, as if the neurons are flipping a coin to decide if they are going to be on or off." Those cycles, which occur on the order of seconds or fractions of seconds, weren't as visible when awake because the wave doesn't propagate much beyond that column, unlike in sleep when the wave spreads across almost the entire brain and is easy to detect.

Our 86 Billion Neurons: She Showed It | by Steven Mithen | The New York Review of Books

And then a surprise: the elephant brain had more neurons than the human brain, not just a few more but three times as many: 247 billion to our 86 billion. But 98 percent of these were located in the cerebellum at the back of the brain, leaving a mere 5.6 billion in the 2.8-kilogram cerebral cortex compared to the 16 billion in the 1.2-kilogram human cerebral cortex. What are all those neurons doing in the elephant cerebellum, ten times more than one would expect? Most likely controlling that other exceptional feature of the elephant, its 100-kilogram and highly sensory muscular trunk.

100 billion neurons, unsourced

She then returned to her alma mater to train young scientists in communication—with an allowance to pursue research if she were so inclined. She was inspired to do so by the pervasive myths about the brain she kept encountering, such as that we use only 10 percent of our capacity. Moreover, none of the distinguished neuroscientists she asked could tell her the source for the claim that there were 100 billion neurons in the brain, which they all believed.

Cooking is the essential human act

Our 86 billion neurons need so much energy that if we shared a way of life with other primates we couldn’t possibly survive: there would be insufficient hours in the day to feed our hungry brain. It needs 500 calories a day to function, which is 25 percent of what our entire body requires. That sounds like a lot, but a single cupful of glucose can fuel the brain for an entire day, with just over a teaspoon being required per hour. Nevertheless, the brains of almost all other vertebrates are responsible for a mere 10 percent of their overall metabolic needs. We evolved and learned a clever trick in our evolutionary past in order to find the time to feed our neuron-packed brains: we began to cook our food. By so doing, more energy could be extracted from the same quantity of plant stuffs or meat than from eating them raw.

Consciousness is tied to 'entropy', say researchers - physicsworld.com

Key to this has been the study of synchronization – how the electrical activity of one set of neurons can oscillate in phase with that of another set. Synchronization in turn implies that those sets of neurons are physically tied to one another, just as oscillating physical systems, such as pendulums, become synchronized when they are connected together. The latest work stems from the observation that consciousness, or at least the proper functioning of brains, is associated not with high or even low degrees of synchronicity between neurons but by middling amounts. Jose Luis Perez Velazquez, a biochemist at the University of Toronto, and colleagues hypothesized that what is maximized during consciousness is not connectivity itself but the number of different ways that a certain degree of connectivity can be achieved.