Tag: Brain

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Norepinephrine: How the Brain Responds to Surprising Events

Brain Surprise Neuroscience
Brain Surprise Neuroscience

According to a new research study, your brain can send out a burst of norepinephrine when it needs you to pay attention to something important.

Unexpected outcomes trigger the release of noradrenaline, which helps the brain focus its attention and learn from the event.

When your brain needs you to pay attention to something important, one way it can do that is to send out a burst of noradrenaline, according to a new MIT study.

This neuromodulator, produced by a structure deep in the brain called the locus coeruleus, can have widespread effects throughout the brain. In a study of mice, the MIT team found that one key role of noradrenaline, also known as norepinephrine, is to help the brain learn from surprising outcomes.

Norepinephrine, also called noradrenaline, is a chemical made by some nerve cells and in the adrenal gland. It can function as both a neurotransmitter (a chemical messenger used by nerve cells) and a hormone (a chemical that travels in the blood and controls the actions of other cells or organs). Norepinephrine is released by the adrenal gland in response to stress and low blood pressure.

“What this work shows is that the locus coeruleus encodes unexpected events, and paying attention to those surprising events is crucial for the brain to take stock of its environment,” says Mriganka Sur, the Newton Professor of Neuroscience in MIT’s Department of Brain and Cognitive Sciences, a member of MIT’s Picower Institute for Learning and Memory, and director of the Simons Center for the Social Brain.

In addition to its role in signaling surprise, the researchers also discovered that noradrenaline helps to stimulate behavior that leads to a reward, particularly in situations where there is uncertainty over whether a reward will be offered.

Sur is the senior author of the new study, which was published on June 1, 2022, in the journal Nature. Vincent Breton-Provencher, a former MIT postdoc who is now an assistant professor at Laval University, and Gabrielle Drummond, an MIT graduate student, are the lead authors of the paper.

Modulating behavior

Noradrenaline is one of several neuromodulators that influence the brain, along with dopamine, serotonin, and acetylcholine. Unlike neurotransmitters, which enable cell-to-cell communication, neuromodulators are released over large swathes of the brain, allowing them to exert more general effects.

“Neuromodulatory substances are thought to perfuse large areas of the brain and thereby alter the excitatory or inhibitory drive that neurons are receiving in a more point-to-point fashion,” Sur says. “This suggests they must have very crucial brain-wide functions that are important for survival and for brain state regulation.”

Brain Locus Coeruleus Nuclei Noradrenaline

Most of the brain’s noradrenaline is produced by the two locus coeruleus nuclei, one in each brain hemisphere. The neurons of the locus coeruleus are labeled with green fluorescent protein. Credit: Gabi Drummond

While scientists have learned much about the role of dopamine in motivation and reward pursuit, less is known about the other neuromodulators, including noradrenaline. It has been linked to arousal and boosting alertness, but too much noradrenaline can lead to anxiety.

Previous studies of the locus coeruleus, the brain’s primary source of noradrenaline, have shown that it receives input from many parts of the brain and also sends its signals far and wide. In the new study, the MIT team set out to study its role in a specific type of learning called reinforcement learning, or learning by trial and error.

For this study, the researchers trained mice to push a lever when they heard a high-frequency tone, but not when they heard a low-frequency tone. When the mice responded correctly to the high-frequency tone, they received water, but if they pushed the lever when they heard a low-frequency tone, they received an unpleasant puff of air.

The mice also learned to push the lever harder when the tones were louder. When the volume was lower, they were more uncertain about whether they should push or not. And, when the researchers inhibited activity of the locus coeruleus, the mice became much more hesitant to push the lever when they heard low volume tones, suggesting that noradrenaline promotes taking a chance on getting a reward in situations where the payoff is uncertain.

“The animal is pushing because it wants a reward, and the locus coeruleus provides critical signals to say, push now, because the reward will come,” Sur says.

The researchers also found that the neurons that generate this noradrenaline signal appear to send most of their output to the motor cortex, which offers more evidence that this signal stimulates the animals to take action.

Signaling surprise

While that initial burst of noradrenaline appears to stimulate the mice to take action, the researchers also found that a second burst often occurs after the trial is finished. When the mice received an expected reward, these bursts were small. However, when the outcome of the trial was a surprise, the bursts were much larger. For example, when a mouse received a puff of air instead of the reward it was expecting, the locus coeruleus sent out a large burst of noradrenaline.

In subsequent trials, that mouse would be much less likely to push the lever when it was uncertain it would receive a reward. “The animal is constantly adjusting its behavior,” Sur says. “Even though it has already learned the task, it’s adjusting its behavior based on what it has just done.”

The mice also showed bursts of noradrenaline on trials when they received an unexpected reward. These bursts appeared to spread noradrenaline to many parts of the brain, including the prefrontal cortex, where planning and other higher cognitive functions occur.

“The surprise-encoding function of the locus coeruleus seem to be much more widespread in the brain, and that may make sense because everything we do is moderated by surprise,” Sur says.

The researchers now plan to explore the possible synergy between noradrenaline and other neuromodulators, especially dopamine, which also responds to unexpected rewards. They also hope to learn more about how the prefrontal cortex stores the short-term memory of the input from the locus coeruleus to help the animals improve their performance in future trials.

Reference: “Spatiotemporal dynamics of noradrenaline during learned behaviour” by Vincent Breton-Provencher, Gabrielle T. Drummond, Jiesi Feng, Yulong Li and Mriganka Sur, 1 June 2022, Nature.
DOI: 10.1038/s41586-022-04782-2

The research was funded, in part, by the Quebec Research Funds, the Natural Sciences and Engineering Research Council of Canada, a NARSAD Young Investigator Award from the Brain and Behavior Research Foundation, the National Institutes of Health, the Simons Foundation Autism Research Initiative through the Simons Center for the Social Brain, the National Natural Science Foundation of China, and the NIH BRAIN Initiative.

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Basolateral amygdala may play a larger, overarching role during naturalistic events

Study provides insights into how early life events can affect brain wiring patterns

The basolateral amygdala (BLA) is a region of the brain that has been almost exclusively studied in the context of fear and emotion. Only recently have researchers begun to question whether the BLA may play a larger, overarching role in memory and behavior. Yet almost nothing is known about the neuronal activity of the BLA during naturalistic behavior.

To address these questions, neuroscientists at the Sainsbury Wellcome Centre at UCL observed the neuronal activity in this brain region while rats freely engaged with a variety of different ethological stimuli. Interactions with ethological stimuli are relevant to the animal’s survival and to the propagation of its genes, and include food, prey and conspecifics. In a new study, published today in Cell Reports, the researchers demonstrate strong responses to these classes of events in the BLA.

The naturalistic stimuli in this study were important to the animals in their everyday life and the rats were naturally curious to interact with them. They included complex multisensory stimuli like male and female rats, food and a moving toy mouse.

Traditionally, research has focused on studying the BLA in rats during trained tasks. Instead, we wanted to observe neuronal activity while rats were freely behaving to see if we could find an overarching role for the BLA during natural behavior that might tie together the previous lines of research.” 

Cristina Mazuski, Research Fellow in the O’Keefe Lab, Sainsbury Wellcome Centre and lead author on the paper

Using Neuropixels, Mazuski and O’Keefe simultaneously recorded from hundreds of neurons in the rat BLA and correlated single-cell neural activity with complex behavior to identify different classes of cells within the BLA that respond to the ethological stimuli. They identified and described two novel categories of cells in the BLA; event-specific neurons, which responded to only one of the four classes of stimuli, and panresponsive neurons, which responded equally well to most or all of the stimuli.

Strikingly, 1/3 of the cells showed an active memory response: not only did the neural response last throughout the entire event but it continued after the end of the event for many minutes. The authors speculate that these after-responses might be acting as a memory system telling the rest of the brain that an important event had just occurred and perhaps alerting other brain regions to store information about other aspects of the event and the circumstances surrounding it.

Commenting on these aspects of the results, Prof. O’Keefe, the senior author on the paper, said “These findings position the basolateral amygdala at the center of the social/ethological brain and open up a whole research program investigating what other naturally-occurring stimuli the rest of the (normally silent) BLA cells are interested in. They also direct our attention to the memory functions of the amygdala which have not, to date, received sufficient consideration”.

As the researchers were recording from many neurons simultaneously using Neuropixels probes, they were also able to look at the circuit connectivity. By delving into the correlated activity between different single neurons, they could infer the flow of information from more-specific neurons such as those responding to female rats or food to the less-specific panresponsive neurons.

“This initial study opens up a lot of future avenues for research. The next steps are to find out what the responses are sensitive to, how robust they are and confirm whether they play a role in memory,” concluded Cristina.

This research received funding from the European Union’s Horizon 2020 research and innovation program under the Marie-Sklodowska-Curie grant agreement No. 840562 to Cristina Mazuski, the Sainsbury Wellcome Centre Core Grant from the Gatsby Charitable Foundation and Wellcome Trust (090843/F/09/Z), and Wellcome Trust Principal Research Fellowship (Wt203020/z/16/z) to John O’Keefe.

Source:

Sainsbury Wellcome Centre

Journal reference:

Mazuski, C & O’Keefe, J., (2022) Representation of Ethological Events by Basolateral Amygdala Neurons. Cell Reports. doi.org/10.1016/j.celrep.2022.110921.

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Dear Abby: My brain keeps reminding me of unhappy events in my past

Dear Abby: My brain keeps reminding me of unhappy events in my past

DEAR ABBY: I’m a divorced woman, soon to be 60, who is often haunted by vivid memories of the past. I constantly recall times in my life that I regret or cringe about, and things I wish I would have handled better. They range from being embarrassed at my 7th birthday party to being bullied from the 5th through 8th grades to awkward moments in high school to parenting decisions I wish I’d made differently.

These memories play over and over like videos in my mind, causing me to feel the emotions again and again. I’ve been through therapy three times in three cities over the past 24 years. One therapist even used eye movement desensitization and reprocessing (EMDR), all to no avail.

I know I can’t go back and change any poor choices or bad decisions, but how can I stop torturing myself over them? Also, would you say it’s normal for people my age to have such vivid memories of what others might have let go of decades ago? — PRISONER OF THE PAST

DEAR PRISONER: People of every age have been known to revisit the past. Some have “conversations” with deceased parents, divorced husbands, old loves, etc.

A technique that might help you would be to get up and move from wherever you are when those flashbacks happen to a new location. Take a 30-minute walk in the sunshine and smell the roses. Count your blessings. And say ALOUD to yourself, “That was THEN. This is NOW.” It is not possible to think of two things at once. Please try it. It’s cheaper than yet another therapist, and it works.

P.S. You are not a “prisoner” of your unhappy past; you CONQUERED it. Congratulations.

DEAR ABBY: I recently married a younger lady and want to know the best way to get her to put her phone down, because she’s texting about 10 hours a day. She works from home now, and if she isn’t working, she’s texting. I feel like I can’t compete, and I’m not sure what to do about it. Please help. — FIGHTING ABOUT THE PHONE

DEAR FIGHTING: Tell your wife you feel like you are in competition with her cellphone, and you don’t like coming out second best. Many people become so caught up in their electronic devices that their relationships suffer, which is why apps have been created that make the addicted more aware of how much time is spent on them. Using the “focus” and “do not disturb” features can also be helpful. I suggest that your wife start using one of them before your marriage deteriorates further.

DEAR ABBY: While driving our car to a babysitting gig, our teenage daughter was asked by the parents to stop at a pizza place and pick up lunch for their child. While pulling into the restaurant’s parking garage, she hit a post, which caused significant damage to the bumper. Should she tell the parents with any expectation that they should offer to pay for some of the repair or is this all on her? — WORK-RELATED IN THE WEST

DEAR WORK-RELATED: I’m sorry, but your daughter should not expect the parents to pay for her fender bender. She can certainly tell them what happened — if she hasn’t already — but with NO expectation that they will help her pay to have her bumper repaired.

Dear Abby is written by Abigail Van Buren, also known as Jeanne Phillips, and was founded by her mother, Pauline Phillips. Contact Dear Abby at www.DearAbby.com or P.O. Box 69440, Los Angeles, CA 90069.

Abby shares more than 100 of her favorite recipes in two booklets: “Abby’s Favorite Recipes” and “More Favorite Recipes by Dear Abby.” Send your name and mailing address, plus check or money order for $16 (U.S. funds), to: Dear Abby, Cookbooklet Set, P.O. Box 447, Mount Morris, IL 61054-0447. (Shipping and handling are included in the price.)

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World events, time change and anger piling on pandemic pressures

World events, time change and anger piling on pandemic pressures






Chuck Norris

Chuck Norris


Don’t care much for the constant mid-March ritual of moving our clocks ahead one hour? According to Beth Ann Malow, a professor of neurology and pediatrics at Vanderbilt University, 63% of Americans would like to see it eliminated.

The thing is, daylight saving time represents much more than a disruption to daily routines. Given the stresses heaped upon us in our world of uncertainties, it could be the proverbial straw that broke the camel’s back.

“Beyond simple inconvenience,” writes Malow on TheConversation.com, “Researchers are discovering that ‘springing ahead’ each March is connected with serious negative health effects.”

“In a 2020 commentary for the journal JAMA Neurology, my co-authors and I reviewed the evidence linking the annual transition to daylight saving time to increased strokes, heart attacks and teen sleep deprivation,” she says.

A separate post on TheConversation.com co-authored by Deepa Burman, co-director of the Pediatric Sleep Evaluation Center at UPMC Children’s Hospital of Pittsburgh, and Hiren Muzumdar, director of the Pediatric Sleep Evaluation Center, notes that sleep deprivation can result in increases of workplace injuries and automobile accidents. One individual’s sleep deprivation can affect an entire family.

People are also reading…

“You may notice more frequent meltdowns, irritability and loss of attention and focus,” they say.

I wonder, could uncontrolled anger be far behind?

Now, watching a devastating war unfold on social media is also hammering away at our collective mental health. We’re all being heightened by graphic and disturbing images that fill our feeds, writes Time magazine reporter Jamie Ducharme.

“Tracking up-to-the-minute developments can come at a cost. … Footage and photos from Ukraine flooding social media and misinformation spreading rampantly (has) implications for public health,” she reports.

It has long been the responsibility of traditional media outlets for editors to decide which content is too graphic to show, or to label disturbing images with warnings. As pointed out by Roxane Cohen Silver, a professor of psychological science at the University of California, Irvine, today anyone “can take pictures and videos and immediately distribute that (on social media) without warning, potentially without thinking about it.”

Jason Steinhauer, founder of the History Communication Institute, says, “Russia has been waging a social media and misinformation war for the past 10 to 12 years.” This has only gotten worse since its invasion of Ukraine.

We should not be surprised at all that studies now suggest that news coverage of the pandemic has contributed to our mental distress. “Adding yet another difficult topic to the mix can worsen those feelings,” Cohen Silver says.

Yet the war is hardly the only attack on our senses. At a time when we are most vulnerable, the Federal Trade Commission reports that predatory fraudsters bilked consumers of an estimated $5.8 billion last year. According to the agency, it represents a 70% increase over 2020. “Almost 2.8 million people filed a fraud complaint, an annual record” and “the highest number on record dating back to 2001,” reports the FTC. “Imposter scams were most prevalent, but investment scams cost the typical victim the most money.”

“Those figures also don’t include reports of identity theft and other categories,” the report points out. “More than 1.4 million Americans also reported being a victim of identity theft in 2021; another 1.5 million filed complaints related to ‘other’ categories (including credit reporting companies failing to investigate disputed information, or debt collectors falsely representing the amount or status of debt).”

The mounting stresses placed upon us are now posing a threat to not just our mental and financial health but our physical well-being.

According to a working paper from researchers at the Naval Postgraduate School and the University of Pennsylvania, “In 2020, the risk of outdoor street crimes initially rose by more than 40% and was consistently between 10-15% higher than it had been in 2019 through the remainder of the year.” Researchers also believe that the finding “points to the potential for other crimes to surge the way homicides have as cities reopen and people return to the streets,” says the report.

Adds Megan McArdle commenting on the report in an op-ed for the Washington Post, “community trust in the police might have plummeted, possibly making people more likely to settle scores on their own. Or police might have reacted to public anger by pulling back from active policing, creating more opportunities for crime.”

Hans Steiner is a professor emeritus of Stanford’s Department of Psychiatry and Behavioral Sciences who has logged decades of work studying anger and aggression. In an interview posted on the Stanford University website, he says he believes that “the coronavirus pandemic, with its extreme disruption of normal daily life and uncertainty for the future, compounded by several other crises (economic distress, racial tension, social inequities, political and ideological conflicts) puts us all to the test: we find ourselves immersed in a pool of negative emotions: fear, sadness, contempt, and yes, anger. What do we do with this forceful emotion?”

“Anger signals that we are being threatened, injured, deprived, robbed of rewards and expectancies,” Steiner says. It should be “one of our adaptive tools to deal with the most difficult circumstances. Sometimes it becomes an obstacle to our struggles, especially when it derails into aggression and even violence.”

Anger problems are now spilling over into record accounts of hate crimes. It seems that today’s circumstances, with anger management and rule of law seemingly at an all-time low, have caused many individuals to become ticking time bombs. Reports CBS News, “the total number of hate crimes nationwide has increased every year but one since 2014, according to FBI data, which includes statistics through 2020.”

Steiner says that “maladaptive anger and aggression has the following characteristics: 1. It arises without any trigger, seemingly out of the blue; 2. it is disproportionate to its trigger in its frequency, intensity, duration and strength; 3. it does not subside after the offending person has apologized; 4. it occurs in a social context which does not sanction anger and aggression.”

Who among us has not seen or maybe even experienced some, maybe all, of these behavior characteristics?

“In such conflicts we need to remind ourselves that diatribes, lies and accusations will not move us forward; compassion, empathy and the reminder that we are all in this horrible situation together (needs to) inspire us,” Steiner advises.

Write to Chuck Norris at info@creators.com with questions about health and fitness.

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Study provides insights into how early life events can affect brain wiring patterns

Study provides insights into how early life events can affect brain wiring patterns

Mar 10 2022

A new study of brain development in mice shortly after birth may provide insights into how early life events can affect wiring patterns in the brain that manifest as disease later in life – specifically such disorders as schizophrenia, epilepsy and autism.

Researchers focused on two types of brain cells that have been linked to adult neurological disorders: neurons in a modulating system nestled deep in the brain and other neurons in the cortex, the brain’s outermost layer, that counteract excitation in other cells using inhibitory effects. The modulating cells send long-range cables to the cortex to remotely influence cortical cell activity.

The study is the first to show that these two types of cells communicate very early in brain development. A chemical released from the modulating cells initiates the branching, or arborization, of axons, the long, slender extensions of nerve cell bodies that transmit messages, on the cortical cells – and that arborization dictates how effective the cells in the cortex are at doing their job.

Though there is still a lot to learn about the impact of this cellular interaction in the postnatal brain, the researchers said the study opens the door to a better understanding of how neurological diseases in adults may relate to early-life events.

It’s known that abnormal early-life experiences can impact kids’ future sensation and behavior. This finding may help explain that kind of mechanism.”


Hiroki Taniguchi, associate professor of pathology, The Ohio State University College of Medicine and senior author of the study

“This study provides new insight into brain development and brain pathology. It’s possible that during development, depending on animals’ experiences, this modulating system activity can be changed and, accordingly, the cortical circuit wiring can be changed.”

Taniguchi completed the work with co-authors André Steinecke and McLean Bolton while he was an investigator at the Max Planck Florida Institute for Neuroscience.

The research is published today (March 9, 2022) in the journal Science Advances.

The study involved chandelier cells, a type of inhibitory neurons in the cortical section of the brain, and neurons of the cholinergic system – one of the systems that monitor the environment and the internal state, and send signals to the rest of the brain to trigger memory and appropriate behaviors.

“Both of these types of cells have been separately studied in the context of adult functions or modulations so far. The developmental role of cholinergic neurons in the brain wiring remains poorly understood,” Taniguchi said.

Chandelier cells are named for the spray of signal-transmitting synapses (called synaptic cartridges) at the branch terminals that resemble candles of a traditional chandelier, a pattern that gives them inhibitory control over hundreds of cells at a time.

“These cells have output control,” said Steinecke, first author of the study who is now working at Neuway Pharma in Germany. “Chandelier cells can put a brake on excitatory cells and tell them they’re not ready to fire. As inhibitory cells, chandelier cells are thought to regulate waves of firing – which is important, because the waves contain information that is transmitted over large distances of the brain.”

Previous post-mortem studies have shown that the synaptic terminals located at the end of chandelier cell axons appear to be reduced in the brains of patients with schizophrenia.

“This axonal ‘arbor’ being reduced suggests they don’t make as many connections to downstream targets, and the connections themselves are also altered and don’t work that well,” Steinecke said.

The team used two techniques to observe chandelier cells during early-life brain development in mice: genetically targeting and using a dye to label and detect cells that differentiate into chandelier cells, and transplanting genetically manipulated cells back into animals shortly after birth. “This enabled us to watch brain development as it happens and manipulate conditions to test what the mechanisms are,” Taniguchi said.

The researchers first observed how chandelier cell axons develop their branching structures, noting that small protrusions emerging from axons were the first signs that branches would sprout. And they identified the chemical needed to start that sprouting process – the neurotransmitter acetylcholine, which is released by cholinergic system cells.

The interaction between the distant cell types was confirmed through a series of experiments: Knocking out receptors that bind to acetylcholine and decreasing activity of cholinergic neurons lessened branch development, and making cholinergic neurons more likely to fire led to more widespread branching.

“The key is that we didn’t previously know how neuromodulatory systems regulate the cortical circuits – and both of them have been implicated in brain diseases,” Taniguchi said. “Now that we’ve found that cholinergic neurons could remotely impact cortical circuit development, especially cortical inhibitory signals, the question is what kind of environment or emotional state of change can impact cortical inhibitors’ development? We may want to see if we can find a link as a next step.”

This work was supported by funding from the Max Planck Society and the Brain Behavior and Research Foundation.

Source:

Journal reference:

Steinecke, A., et al. (2022) Neuromodulatory control of inhibitory network arborization in the developing postnatal neocortex. Science Advances. doi.org/10.1126/sciadv.abe7192.

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Cell stress-related biochemical events may be partly driving Parkinson’s disease

Cell stress-related biochemical events may be partly driving Parkinson's disease

Parkinson’s disease may be driven in part by cell stress-related biochemical events that disrupt a key cellular cleanup system, leading to the spread of harmful protein aggregates in the brain, according to a new study from scientists at Scripps Research.

The discovery, published in The Journal of Neuroscience in February 2022, offers a clear and testable hypothesis about the progression of Parkinson’s disease, and may lead to treatments capable of significantly slowing or even stopping it.

We think our findings about this apparent disease-driving process are important for developing compounds that can specifically inhibit the process of disease spread in the brain.”


Stuart Lipton, MD, PhD, study senior author, Step Family Endowed Chair, founding co-director of the Neurodegeneration New Medicines Center, and professor in the Department of Molecular Medicine at Scripps Research

Parkinson’s disease affects roughly one million people in the United States. Its precise trigger is unknown, but it entails the deaths of neurons in a characteristic sequence through key brain regions. The killing of one small set of dopamine-producing neurons in the midbrain leads to the classic Parkinsonian tremor and other movement impairments. Harm to other brain regions results in various other disease signs including dementia in late stages of Parkinson’s. A closely related syndrome in which dementia occurs early in the disease course is called Lewy Body Dementia (LBD), and affects about 1.4 million people in the U.S.

In both diseases, affected neurons contain abnormal protein aggregations, known as Lewy bodies, whose predominant ingredient is a protein called alpha-synuclein. Prior studies have shown that alpha-synuclein aggregates can spread from neuron to neuron in Parkinson’s and LBD, apparently transmitting the disease process through the brain. But precisely how alpha-synuclein aggregates build up and spread in this way has been unclear.

One clue, uncovered by Lipton’s lab and others in prior research, is that the Parkinson’s/LBD disease process generates highly reactive nitrogen-containing molecules including nitric oxide. In principle, these reactive nitrogen molecules could disrupt important cellular systems, including “housekeeping” systems that normally keep protein aggregates under control.

In the new study, the Scripps Research team demonstrated the validity of this idea by showing that a type of nitrogen-molecule reaction called S-nitrosylation can affect an important cellular protein called p62, triggering the buildup and spread of alpha-synuclein aggregates.

The p62 protein normally assists in autophagy, a waste-management system that helps cells get rid of potentially harmful protein aggregates. The researchers found evidence that in cell and animal models of Parkinson’s, p62 is S-nitrosylated at abnormally high levels in affected neurons. This alteration of p62 inhibits autophagy, causing a buildup of alpha-synuclein aggregates. The buildup of aggregates, in turn, leads to the secretion of the aggregates by affected neurons, and some of these aggregates are taken up by nearby neurons.

“The process we observed seems very similar to what is seen in Parkinson’s and LBD brains,” says study first author Chang-Ki Oh, PhD, a staff scientist in the Lipton laboratory.

The researchers also tested postmortem brains of LBD patients, and again found that levels of S-nitrosylated p62 were abnormally high in affected brain areas-;supporting the idea that this process occurs in humans.

Lipton and Oh say that S-nitrosylation of proteins becomes more likely in many situations of cellular stress, including the presence of protein aggregates. Thus, this chemical modification of p62 could be a key factor in a self-reinforcing process that not only stresses brain cells beyond their limits, but also spreads the source of stress to other brain cells.

The team is now working to develop drug-like compounds that specifically inhibit the S-nitrosylation of p62. Although it would take years to develop such compounds as potential commercial drugs, they could, in principle, slow the Parkinson’s/LBD disease process or prevent its further spread in the brain after it begins, Lipton says.

Source:

Scripps Research Institute

Journal reference:

Oh, C., et al. (2022) S-Nitrosylation of p62 Inhibits Autophagic Flux to Promote α-Synuclein Secretion and Spread in Parkinson’s Disease and Lewy Body Dementia. Journal of Neuroscience. doi.org/10.1523/JNEUROSCI.1508-21.2022.

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Dying brain may recall key life events

Dying brain may recall key life events

Scientists may be closer to answering an age-old question about what happens to the human brain as we die.

Neuroscientists accidentally recorded a dying brain while they were using electroencephalography (EEG) to detect and treat seizures in an 87-year-old man and the patient suffered a heart attack.

It was the first time ever that scientists had recorded the activity of a dying human brain.

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The rhythmic brain wave patterns which were recorded during the man’s time of death were observed to be similar to those occurring during dreaming, memory recall and meditation.

The unexpected event allowed scientists to conduct a study into what they recorded – the findings from which have just been published in Frontiers in Aging Neuroscience.

According to the study’s organiser, Dr Ajmal Zemmar, a neurosurgeon at the University of Louisville, its findings suggest that our brains may remain active and coordinated during and even after the transition to death.

Furthermore, the specific type of brain waves which were recorded in the dying brain – called neural oscillations – suggest the person was seeing their lives flash before their eyes through “memory retrieval”.

“We measured 900 seconds of brain activity around the time of death and set a specific focus to investigate what happened in the 30 seconds before and after the heart stopped beating,” Dr Zemmar told Frontiers Science News.

“Just before and after the heart stopped working, we saw changes in a specific band of neural oscillations, so-called gamma oscillations, but also in others such as delta, theta, alpha, and beta oscillations.

“Through generating oscillations involved in memory retrieval, the brain may be playing a last recall of important life events just before we die, similar to the ones reported in near-death experiences.

“These findings challenge our understanding of when exactly life ends and generate important subsequent questions, such as those related to the timing of organ donation.”

While the first-of-its-kind study is based on a single case that additionally involved a patient who was suffering from epilepsy and swelling, Dr Zemmar said he hopes to investigate more cases.

He added that the results gave neuroscientists hope to better understanding the “life recall” phenomenon which is often reported by those who have had near-death experiences.

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Biological events occurring during puberty trigger sex differences in learning and memory

Biological events occurring during puberty trigger sex differences in learning and memory

New research from the University of California, Irvine reveals that sex differences in learning and memory mechanisms are triggered by biological events occurring during puberty. Findings show prepubescent female rodents have much better hippocampal long-term potentiation (LTP) and spatial learning than same-age males, but puberty has opposite consequences for synaptic plasticity in the two sexes.

The study, titled “Prepubescent female rodents have enhanced hippocampal LTP and learning relative to males, reversing in adulthood as inhibition increases” was recently published in Nature Neuroscience.

Since the late 19th century, the general consensus in the scientific community has been that men outperform women on spatial tasks, while women excel in learning tasks involving verbal material, while the general debate has been about why there is a difference.

The surprising conclusion from our results is that the polarization of sex differences in hippocampal synapses and related learning reverses in females and males from before to after puberty. This occurs because of distinct developmental changes. Thresholds for plasticity and encoding spatial information increase in females and decease in males.”


Christine Gall, PhD, co-corresponding author, and distinguished professor and chair of anatomy and neurobiology at the UCI School of Medicine

Puberty is a critical landmark in brain maturation and results in a wide variety of sex differences in behavior, but little is known about how it affects the substrates for memory encoding. Researchers identified a female-specific mechanism that increases the LTP threshold and decreases spatial memory from before to after puberty. Sex differences were demonstrated for hippocampus-dependent processes and driven by different underlying mechanisms.

In females only, inhibitory synapses in the CA1 field of the hippocampus exhibit an increase in levels of GABAA receptors containing the α5 subunit; this increase is associated with greater inhibition of synaptic activity critical for synaptic plasticity and memory. The α5 receptors have been linked to anxiety which also undergoes changes at the onset of the estrous cycle. Researchers found that pharmacological suppression of α5-GABAA receptors restored LTP and memory encoding in females to levels observed before puberty.

“Our team proposes that the emergent female pattern may favor learning in complex circumstances while the emergent male pattern favors rapid acquisition of simpler material. This idea suggests that optimal teaching strategies need to reflect previously unsuspected brain differences between the sexes and how these are dramatically adjusted during puberty,” Gall said. “The vast majority of studies have begun with analyses of young adult male rodents. Females use somewhat different memory mechanisms than do males and therefore may respond differently to drugs and gene mutations. This new research demonstrates the need for new sexually differentiated approaches for the development of therapeutic treatments and their applications at different life stages.”

Further research will be conducted to determine if the sex-specific LTP threshold changes identified in hippocampus during the transition to postpubertal life are evident in other brain areas and influence the encoding of different types of memories.

Source:

University of California, Irvine

Journal reference:

Le, A.A., et al. (2022) Prepubescent female rodents have enhanced hippocampal LTP and learning relative to males, reversing in adulthood as inhibition increases. Nature Neuroscience. doi.org/10.1038/s41593-021-01001-5.