Thicker Nerve Fibres Enable Faster Reactions In Mice (Neuroscience)

Maria Eichel and colleagues have succeeded in genetically switching off the CMTM6 protein in myelin-producing cells in mice. They subsequently observed that the mice not only developed thicker axons, but also reacted significantly more quickly to sensory stimuli compared to their peers. Since neurological diseases such as Charcot-Marie-Tooth disease exhibit reduced axon diameter, CMTM6 could present a possible target for therapies.

Electron microscope image of axons in cross section. Mice lacking the gene CMTM6 (right) have thicker axons than animals with a functional gene (left). Credit: MPI f. Experimental Medicine/ Möbius

In order to flee from a predator or to hunt successfully, animals have to be able to react swiftly to external stimuli. The nerve cells conduct electrical impulses along their extensions—the axons—culminating in a contraction of the muscles. One of the factors influencing the speed with which this signal transmission occurs is the diameter of the axons. Thicker axons offer less resistance to the electrical signal, enabling swifter transmission. Invertebrates such as squid have some very large axons which achieve high transmissions speeds.

By contrast, the speed of signal transmission in the vertebrate nervous system has increased by a different evolutionary process. Myelin formed, surrounding and electrically insulating the nerve fibers with a multi-layered, fat-rich sheath. Myelin enables a fast stimulus conduction even in axons with a small diameter.

There are many reasons why this has an advantage for vertebrates: smaller axons not only use less energy, they also need less space. More axons can fit into one nerve path, enabling a greater precision in signal conduction and the development of complex cognitive functions. Insulating the axons also enables rapid signal transmission over long ranges, such as in larger animals like the giraffe. The myelin-forming cells in the peripheral nervous system, known as Schwann cells, are wound tightly around the axons. Whether this interaction limits the diameter of the axons, and to what extent, has been unclear until now.

Unknown protein in Schwann cells

Hauke Werner, along with a working group from the Max Planck Institute for Experimental Medicine in Göttingen are researching the link between myelin and axon function. Together with researchers at the University of Göttingen, the University of Leipzig, the University of Mainz and the Max Planck Institute for Medical Research, they have been researching a previously unknown protein in the Schwann cells, which sits in direct contact with the axons.

In their study, the researchers genetically switched off protein CMTM6 (chemokine-like factor-like MARVEL-transmembrane domain-containing family member-6) in the Schwann cells of mice. As a result, the mice developed significantly thicker axons than their peers. Electrophysiological investigations of the nerve cells showed an increased neural transmission speed in the mice. Other components of the nervous system were unaffected, leading the researchers to conclude that the increase in signal transmission speed could be attributed to the thicker axons.

Faster reactions

The researchers also observed faster reactions in the behavior of the mice. “When we put the mice on a heated tile, the mice with thicker axons reacted significantly faster to the heat stimulus,” explains Maria Eichel, a colleague of Hauke Werner and first author of the study. However, the swifter signal transmission also caused problems for the mice. When the researchers set the mice to run over a grating, the genetically modified mice slipped on the bars more often than their peers. “The animals were probably experiencing problems correctly coordinating the rapidly-transmitted stimuli,” explains Eichel.

While switching off the CMTM6 protein did not create super-mice, the experiments with these genetically modified animals do however deliver a possible foundation for therapies for neuronal diseases. Many of these diseases are characterized by impaired signal transmission. In patients with Charcot-Marie-Tooth disease, reduced axon diameter is one cause. “The CMTM6 protein could be a starting point for therapies for diseases such as this,” says Eichel. The researchers’ next step will be to take mice which develop particular neurological diseases as a result of genetic modification, and also switch off the CMTM6 protein, to investigate whether their condition is improved.

This article is republished from max planck gesellschaft

References: Eichel, M.A., Gargareta, V., D’Este, E. et al. CMTM6 expressed on the adaxonal Schwann cell surface restricts axonal diameters in peripheral nerves. Nat Commun 11, 4514 (2020). https://doi.org/10.1038/s41467-020-18172-7 link: https://www.nature.com/articles/s41467-020-18172-7

How Fear Persists In The Mouse Brain? (Neuroscience)

Mice exhibit fear responses to threats, such as the presence of a rat, and these behaviors appear to linger even after the threat is gone. What is happening in the mouse brain at the cellular level during these persistent displays of fear behavior? A team of neuroscientists answered this question in their new paper.

They discovered the neural mechanisms underlying persistent fear responses. Surprisingly, the team discovered that these persistent responses are encoded in a center of the brain that was thought to be much more evolutionarily primitive and reflexive.

“The overarching significance of our findings is that they show that persistent fear states are not due simply to persistently elevated stress hormones, as traditionally thought, but also involve persistent electrical activity in the brain,” says Anderson. “It is surprising to find such neural dynamics in the hypothalamus”—a fundamental region of the brain found in all vertebrates including humans—”since this type of persistent activity is more often associated with cognitive functions, such as working memory, in the cortex.”

Mice have a well-characterized repertoire of defensive behaviors, such as freezing and fleeing. In the study, the team focused on a particular facet of mice’s fear response to rats: when a rat is present in a mouse’s experimental arena, the mouse will hug up against the walls of the space instead of roaming freely around.

In their study, the researchers specifically focused on a brain region called the ventromedial hypothalamus (VMH). In 2015, researchers from the Anderson lab discovered that the VMH encodes for defensive behaviors in mice.

“The hypothalamus is generally thought by neuroscientists to be a primitive area, controlling reflexes in a robotic way. Neurons receive a stimulus, react accordingly, and shut off again,” says Kennedy, who is now a professor of physiology at Northwestern University. “Our work shows that this is not always the case.”

In this new research, the team found that VMH neurons are activated when presented with a threat—the nearby rat—and that they stay active for tens of seconds even after the rat is taken away. In general, neurons are usually only active for a few milliseconds. The team also found that they could induce mice to display fear behaviors by artificially stimulating these neurons, and essentially make mice unafraid by artificially silencing them.

Because the lingering fear response might be due to some lingering rat odor, the researchers examined mice’s fear response when they were presented with only sounds at the precise frequency at which rats vocalize. In this case, the mice also displayed persistent fear behavior and their VMH neurons were persistently active, again for tens of seconds, after the sound ceased.

The team then took a closer look at the activity of individual neurons in the VMH, instead of just the overall activity of the area. This would be like examining the individual activity of each musician in an orchestra, instead of listening to the whole orchestra playing together. Measuring individual neuron activity showed that there were two distinct populations of neurons that each responded to the two different types of threats—rat sound versus rat presence.

How did the persistent neural activity last for tens of seconds, when neurons only fire in bursts of activity on the order of milliseconds? Two possible mechanisms might explain this. First, the neurons may form a so-called neural feedback loop that causes their sequential activation, like runners passing a baton during a relay; or second, the neurons may release chemicals into their environment that keep triggering their re-activation. Alternatively, a combination of both scenarios—a neural feedback loop and the release of neurochemicals—might be at play.

Kennedy developed neural networks to model the first scenario, the second scenario, and combinations of the two to find out which would accurately predict the persistent neural activity following a stimulus as well as the identity of the stimulus (i.e., the actual presence of a rat or only the sound of a rat). Only the combination models could explain both of these features.

References: Kennedy, A., Kunwar, P.S., Li, L. et al. Stimulus-specific hypothalamic encoding of a persistent defensive state. Nature (2020). https://doi.org/10.1038/s41586-020-2728-4 link: https://www.nature.com/articles/s41586-020-2728-4

Researchers Pointed Out Another Job Of Immune System– ‘Combatting Depression’ (Neuroscience)

An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects. The new research suggested that these immune cells may play a role other than protecting against microbial invaders—protecting our mental health.

The results buttress an emerging theory that gamma interferons, a type of immune cell that helps induce and modulate a variety of immune system responses, may also play a role in preventing depression in healthy people.

Previous research has shown that blocking gamma interferons and the T cells they help produce can cause depression-like symptoms in mice. Hafler notes that depression is also a common side effect in patients with MS treated with a different type of interferon.

Using a powerful new technology that allows a detailed examination of individual cells, the researchers show that while the characteristics of T cells in the spinal fluid of healthy people share similarities with those of MS patients, they lack the ability to replicate and cause the damaging inflammatory response seen in autoimmune diseases such as MS.

In essence, the immune system in the brains of all people is poised to make an inflammatory immune system response and may have another function than defending against pathogens.

These T cells serve another purpose and we speculate that they may help preserve our mental health.

According to Hafler they planned to explore how immune system responses in the central nervous system might affect psychiatric disorders such as depression.

References: J.L. Pappalardo el al., “Transcriptomic and clonal characterization of T cells in the human central nervous system,” Science Immunology (2020), Vol. 5, Issue 51, eabb8786 DOI: 10.1126/sciimmunol.abb8786 link: https://immunology.sciencemag.org/content/5/51/eabb8786

Your Drunk Self May Actually Be Real You (Psychology)

Who do you become when you drink a little too much alcohol? Maybe you’re the party animal, dancing on tables and singing at the top of your lungs. Maybe you’re the drama queen, getting teary-eyed and overly emotional over a text you sent your ex two months ago. Or perhaps you’re the ray of sunshine, complimenting the outfits of everyone at the bar and insisting you’ll all hang out sometime. According to research, your drunk alter ego isn’t a separate identity at all. That’s the real you, pal.

If you’re of legal drinking age, we’ve got news — whether it’s news you’re ready to cope with or not. Research says that your drunk self is probably not as far off from your actual personality as you think it is. Though it may feel like you’re a completely different person when you’re in the club getting tipsy, a 2017 study published in Clinical Psychological Science found that your drunk persona doesn’t differ from your sober one, more or less. Basically, you’re always that special, unique, wonderful you, no matter how many tequila shots you foolishly ended up taking on your birthday.

For the study, the researchers from University of Missouri and Purdue University sought to find out if “drunk personalities” are a thing or not. They specifically tested if “differences between sober and intoxicated personality expression can be observed reliably” by friends during some drunk game-playing. Two weeks prior to the experiment, the researchers had the 156 participants complete surveys describing their typical sober and drunk personalities. Next, the team gave half of the participants booze, then had their friends join them in the lab to play games meant to bring out different personality traits. The drinkers rated their own in-the-moment personality traits during the session while trained (and sober) raters assessed the same traits. While the drinkers noted personality differences in themselves while drunk, the sober onlookers didn’t see any big differences between their sober and drunk personalities. Except for one thing: the drinks made those participants more extroverted. Obviously.

“We were surprised to find such a discrepancy between drinkers’ perceptions of their own alcohol-induced personalities and how observers perceived them,” said lead author Rachel Winograd, a psychological scientist at University of Missouri, in a press release. “Participants reported experiencing differences in all factors of the Five Factor Model of personality, but extraversion was the only factor robustly perceived to be different across participants in alcohol and sober conditions.”

As for why you feel like an entirely different being when you’ve been a bit overserved? Probably just the placebo effect. If you have it in your head that tequila makes you wild or wine makes you emotional, you’ll make those expectations come true all on your own. Kind of impressive, actually. Cheers!

This 10-Min Personality Test Can Measure You On The 5 Main Personality Traits (Psychology)

We’ve told you about therapy before, but there’s something about the business of mental health that’s hard to quantify. A medical doctor can tell you if you’ve got a fever or if your arm is broken, but how can you measure exactly how neurotic you are? Easy: take this test.

Welcome to the OCEAN. That’s short for Openness to experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism, and it’s the five-point personality profile some professionals use to assess the psychological states of their patients.

The International Personality Item Pool can help you find out exactly where you place on the board. There are two versions. The 300-point test is perhaps more accurate, but psychology professor John Johnson (who put together this online resource) warns that it can take up to 40 minutes, and worse, the website tends to crash. So you may want to try the 120-point test instead since you’ll only lose 15 minutes tops if the internet eats your results.

Even 120 questions sounds like a lot, but they go by pretty quickly. The points are just short statements of things you might do, such as “keep your promises” and “go on binges,” and you answer on a scale from “very inaccurate” to “accurate” regarding how they apply to you. When you get your results back, you’ll be ranked on exactly how open to new experiences, conscientious, extroverted, agreeable, and neurotic you are. If you really want to know, that is.

The thing is, the test is grading you on more than just the Big Five. Each of those personality traits can be split into smaller pieces for greater precision. So under “Extraversion,” you’re actually being graded on things like “assertiveness,” “friendliness,” and “cheerfulness.” “Agreeableness” includes “trust,” “morality,” and “modesty.” And dark-horse personality trait “Neuroticism” includes such traits as “anxiety,” “anger,” “depression,” and “self-consciousness.”

Just remember that the test isn’t actually a judgment of your worth or quality as a person. Even if, for example, you get a low score on “morality,” that might just mean you are more guarded than others, or that you are less open with the truth than the average person. It’s probably a trait that should be examined, sure. Just don’t mistake it for saying you’re a bad person.

Psychotherapy Works, Even When You Feel Like It Doesn’t (Psychology)

Have you ever made an appointment with a psychotherapist? It’s a scary thing to do, and that first meeting is never easy. Even as time goes on, you might feel sometimes like you’re just spinning your wheels in every session, since the balm for your neuroses doesn’t really come all at once. But we have good news. A new meta-analysis published in the Psychological Bulletin suggests that therapy works — no matter what kind of therapy it is.

Personality isn’t entirely static, but it’s not the most pliable thing in the world either. If you’re very outgoing and adventurous in your 20s, you’ll probably be the same in your 30s and 40s. Age and life experiences will take their toll as well, and as you grow older it’s likely that you’ll grow more self-confident, more controlled, and more emotionally stable. That’s great news for everyone who’s moving forward in time. But this new meta-analysis suggests that if time isn’t changing you fast enough, a trip to the doctor might.

The researchers squared their focus on what’s known as the “Big Five” of personality traits: Openness to experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism (collectively known as OCEAN). Therapy was particularly useful in altering neurotic tendencies. Neuroticism tends to decrease as you age from young adulthood into middle age, but just four weeks of therapy was enough to affect about half of the average lifetime shift towards a calmer mind. Therapy had a pretty significant effect on Extraversion as well, and a smaller effect on Conscientiousness and Agreeableness. Only changes to Openness to experiences were inconsistent across the 207 this meta-analysis amalgamated.

Most interestingly of all, the study spans multiple types of psychotherapy, so when it comes to choosing a doctor, you should find one who practices a style that makes you comfortable — when it comes to effectiveness, they’re all pretty similar.

The thing is, the actual style your psychotherapist practice isn’t often high on the list of qualities you look for — it’s certainly lower than if they’re on your insurance or not, and it all depends on if you even know the difference between them. So we thought we’d demystify the different varieties and ease the process along.

Cognitive-Behavioral Therapy

The current reigning champ of psychotherapy, CBT focuses, as you might guess, on both thoughts and behaviors. This might take a couple of different forms. Your therapist could help you process difficult thoughts and emotions, and encourage more healthy ones instead with the goal of altering your behavior. But they might also encourage you to alter your behavior first, for example, suggesting that a person with social anxiety attend a crowded event with an eye towards changing the harmful thought processes. A lot of emphasis is placed on understanding your thought processes and either overcoming them or using them to your advantage. CBT is often recommended for anxiety disorders, depression, substance abuse, and eating disorders.

Psychodynamic Therapy

Psychodynamic therapy has fallen a bit out of favor these days, but its roots go all the way back to Freud. In this sort of practice, the patient is encouraged to explore the relationship between their conscious and their unconscious mind, with many unconscious thoughts being linked to early childhood experiences. The therapist may also emphasize mental and behavioral patterns, and help the patient uncover the underlying reasons for repeating these patterns. The entire process is generally regarded as being slower than CBT, and thus it can be a bit harder to find an insurance company that covers it. It’s recommended for patients with generalized anxiety disorders and depression.

Person-Centered Therapy

Person-centered therapy sets itself apart from the other two varieties by having a lot less structure and putting a lot more emphasis on the relationship between the patient and the therapist. The patient is encouraged to work through their thoughts on their own time, with only a little guidance. One of the main advantages of this sort of work is that it de-emphasizes the “authority” aspect of the therapist in favor of reminding the patient that we’re all human beings with our own ways of processing. It’s often recommended for people who haven’t been diagnosed with anything but do suffer low self-esteem, body image issues, and relationship problems.

Coffee Could Help You Tolerate The People You Work With (Psychology)

Coffee drinkers know how crucial the brown stuff is for workplace productivity. If you’ve ever cold-shouldered a colleague for daring to bother you before your morning coffee, the following will come as no surprise. According to research, drinking coffee can help you stop being such a crabby pants in group settings.

If you regularly drink a cup of joe or five at the office, don’t stop now. An April 2018 study published in the Journal of Psychopharmacology found that when coffee drinkers downed a cup of java before a group discussion, they stayed focused and felt better about themselves and the other people in the conversation. That lines up with how most workers feel. According to a 2015 survey, 71 percent of city-dwelling people in the U.S. agree that coffee is integral to a successful meeting.

“We see coffee being served in many meetings but found very little research on how coffee might affect group dynamics. Most research is about how coffee affects an individual. So, we decided to study the effects (if any), of consumption of coffee on performance of individuals in a group, and the collective output of the group,” study author Vasu Unnava of the University of California, Davis tells PsyPost.

For the small study, researchers had 134 college students break into groups to discuss the Occupy Wall Street movement for 15 minutes. The researchers told some of the coffee-drinking participants to hold off on the brew for a few hours prior to the discussion, then gave them caffeinated coffee just before the meeting. These people, all geared up on coffee, were better at focusing on the topic at hand and viewed the people they were chatting with more favorably.

“The study was conducted using people who consume coffee regularly,” Unnava said. “For these people, it looks like coffee does make them feel more alert, focuses their thinking on the topic or task at hand, and has them participate more in group tasks. So, if you are a coffee drinker, it looks like coffee helps you do better in group tasks.”

Though all you coffee drinkers out there are probably all nodding your heads in unison, the study has a few caveats. “A major caveat is that our coffee drinkers came to the study after staying away from coffee for a few hours,” Unnava told PsyPost. “So, we do not know if the coffee they consumed in the study increased their alertness or it is the decreased alertness in those who consumed decaffeinated coffee that caused the effects reported in the study.”

“Second, we used a topic that the participants generally agreed on. What the results might be if there is disagreement is an interesting issue to study further. Finally, we used only one type of task — group discussion. How coffee may affect people’s performance in other kinds of tasks (e.g., group problem solving, group physical work) is not known.” Just to be on the safe side, we’ll keep the coffee coming regardless.

How Can We Communicate With Humans Of The Future Without Using Language? (Language / Science)

We take for granted that trying to communicate with alien species could be challenging, but what about with our own species 10,000 years in the future? This is the problem faced by agencies charged with safely disposing of nuclear waste. This waste stays dangerous to humans for thousands of years, so in order to protect future humans, there must be some way of telling them to avoid sites where nuclear waste is stored.

There is no guarantee that any of the languages, symbols, or cultural references we have today will make any sense to the people of the future. So how can we make sure our warnings about the dangers of nuclear waste disposal sites will be heeded? In 1981, the U.S. Department of Energy convened a panel of experts for something called the Human Interference Task Force to study the problem and issue a report. They came up with various ideas for the 10,000-year communication task, all of which have drawbacks.

Why langauge won’t work? Language never stops changing. From generation to generation both the form and meanings of words shift in subtle ways that we hardly recognize while the changes are in progress, but after just a few hundred years are significant enough to keep us from understanding. Chaucer’s English, which is only 600 years old, can only be understood by people with special training. Linear A, a form of writing found on a tablet that is significantly less than 10,000 years old, has still not been deciphered.

The most useful approach to take with language on a marker to last 10,000 years into the future is extreme redundancy. The Rosetta Stone was deciphered because it had the same text in three different languages, one of which, Greek, was accessible to scholars. If the same message is written in many different languages and scripts, there is no guarantee that people of the future will know how to interpret them, but the chances of interpretation increase a little.

Why symbols won’t work? We do have some symbols that can transcend language; for example, numerals and mathematical symbols, and airport markers for customs, luggage, and restrooms. There are various international symbols for danger, and even a specific one for nuclear radiation. But they depend heavily on cultural conventions which may not exist even a century from now. Symbols must be interpreted within a context of what is already known or assumed, and we can’t predict what the background context will be in the future. Maybe a skull and crossbones will look enticing if it is interpreted as a marker for the tomb of an important person and may contain treasure.

Other ways to emphasize the idea of danger may backfire in a similar way. Having the area covered in an unnatural color or sharp spikes would work to call attention to it, and if humans of the future are anything like us, their curiosity will draw them toward what captures the attention.

In a report issued for the Office of Nuclear Waste Isolation in 1984, semiotician Thomas Sebeok recommended a strategy to bridge the linguistic and cultural changes that could render a message meaningless in 10,000 years; he proposed that the warning should contain within it a “metamessage” advising that every 250 years, it should be re-encoded into whatever the current communication strategies of the time are. But how can we make sure people of the future comply?

He thought the best chance of success was a created mythology: a folklore passed along through rituals and legends. It would be overseen by an “atomic priesthood” or group of scientists that knew the real dangers and would encourage the development of a deep cultural taboo and fear of dire consequences from non-compliance. Even if the reason for the atomic priesthood were to be forgotten and the legends and stories transform into something else, there was a chance a superstition and aura of danger would linger and offer some protection.

But this would still be no guarantee. We have no idea what the future will look like or how any messages we send will be interpreted. We can only go on the hunch that the people of the future will be, at least in some ways, like us.

These Are The Words That Make You Say ‘Um’ (Language /Neuroscience)

There’s a certain kind of word that slows you down more than any other — that is, it’s more likely that you’ll have to pause and use a filler word like “um” or “er” before your tongue finally comes up with the word you’re looking for. Let’s guess what kind of word it is. Hmm … maybe taxonomic classifications? Or maybe it’s the names of your in-laws and their extended family members? No, wait, it’s got to be the infield fly rule. Actually, the words that make our brains hit the brakes are some of the most common words of all.

It’s nouns. You know: people, places, and things. Probably the easiest part of speech to wrap your mind around — a whole lot easier than gerunds. What is it that makes words like “shirt,” “mug,” and “toffee apple” the speed bumps of language? Whatever it is, it’s true in English, Dutch, and various languages of the Amazon, Siberia, and the Kalahari desert. When a team led by Frank Seifart from the University of Amsterdam and Professor Balthasar Bickel from the University of Zurich examined native speakers of a broad range of languages, they were able to see that some patterns hold true across linguistic borders. They were listening for brief pauses and filler words, such as “um” or “uh,” and found that these tended to pile up before references to concrete objects and concepts.

Why would this be? The researchers believe that it’s because when you use a noun, it’s usually because you are introducing a new concept into the conversation. Unlike verbs and adjectives, nouns can be mediated by pronouns. That means that if you’ve already referred to the thing you’re talking about, you can often avoid mentioning it by either using a pronoun or avoiding it entirely. For example, you might say “My dog went outside and it played fetch,” or just “My dog went outside and played fetch.” When you actually use the noun “dog,” chances are that it’s the first time a dog is being brought up in this particular conversation. You’re more likely to have to reel in your conversational flow and slow down to redirect the topic when you’re using a noun than you are for any other part of speech. No wonder they slow us down.

It’s clear that the way that we use a word changes depending on what type of word it is. But there’s MRI evidence that the brain processes different parts of speech differently as well. In 2010, researchers from Spain and Germany taught participants several made-up words, split into nouns and verbs. Their task was to work out the meaning of each word from context alone — from the sentences “The girl got a jat for Christmas” and “The best man was so nervous he forgot the jat,” you can figure out that “jat” means “ring,” for example. As it turns out, unfamiliar nouns caused activity in the area of the brain most associated with visual and object processing, while strange verbs sparked something in the semantic, conceptual, and grammar-oriented areas. It all goes to show how there isn’t a “language” region of the brain — language is so essential that you’ve got a special place for every part of it.