Monthly Archives: December 2023

Neuroscience

Anthrobots: Tiny Biobots From Human Cells Heal Neurons – Neuroscience News

Summary: Researchers developed Anthrobots, microscopic biological robots made from human tracheal cells, demonstrating potential in healing and regenerative medicine.

These self-assembling multicellular robots, ranging from hair-width to pencil-point size, show remarkable healing effects, particularly in neuron growth across damaged areas in lab conditions.

Building on earlier Xenobot research, this study reveals that Anthrobots can be created from adult human cells without genetic modification, offering a new approach to patient-specific therapeutic tools.

Key Facts:

Source: Tufts University

Researchers at Tufts University and Harvard Universitys Wyss Institute have created tiny biological robots that they call Anthrobots from human tracheal cells that can move across a surface and have been found to encourage the growth of neurons across a region of damage in a lab dish.

The multicellular robots, ranging in size from the width of a human hair to the point of a sharpened pencil, were made to self-assemble and shown to have a remarkable healing effect on other cells. The discovery is a starting point for the researchers vision to use patient-derived biobots as new therapeutic tools for regeneration, healing, and treatment of disease.

The work follows from earlier research in the laboratories of Michael Levin, Vannevar Bush Professor of Biology at Tufts UniversitySchool of Arts & Sciences, and Josh Bongard at the University of Vermont in which they created multicellular biological robots from frog embryo cells calledXenobots, capable of navigating passageways, collecting material,recording information, healing themselves from injury, and evenreplicating for a few cycleson their own.

At the time, researchers did not know if these capabilities were dependent on their being derived from an amphibian embryo, or if biobots could be constructed from cells of other species.

In the current study, published inAdvanced Science, Levin, along with PhD student Gizem Gumuskaya discovered that bots can in fact be created from adult human cells without any genetic modification and they are demonstrating some capabilities beyond what was observed with the Xenobots.

The discovery starts to answer a broader question that the lab has posedwhat are the rules that govern how cells assemble and work together in the body, and can the cells be taken out of their natural context and recombined into different body plans to carry out other functions by design?

In this case, researchers gave human cells, after decades of quiet life in the trachea, a chance to reboot and find ways of creating new structures and tasks.

We wanted to probe what cells can do besides create default features in the body, said Gumuskaya, who earned a degree in architecture before coming into biology.

By reprogramming interactions between cells, new multicellular structures can be created, analogous to the way stone and brick can be arranged into different structural elements like walls, archways or columns.

The researchers found that not only could the cells create new multicellular shapes, but they could move in different ways over a surface of human neurons grown in a lab dish and encourage new growth to fill in gaps caused by scratching the layer of cells.

Exactly how the Anthrobots encourage growth of neurons is not yet clear, but the researchers confirmed that neurons grew under the area covered by a clustered assembly of Anthrobots, which they called a superbot.

The cellular assemblies we construct in the lab can have capabilities that go beyond what they do in the body, said Levin, who also serves as the director of the Allen Discovery Center at Tufts and is an associate faculty member of the Wyss Institute. It is fascinating and completely unexpected that normal patient tracheal cells, without modifying their DNA, can move on their own and encourage neuron growth across a region of damage, said Levin.

Were now looking at how the healing mechanism works, and asking what else these constructs can do.

The advantages of using human cells include the ability to construct bots from a patients own cells to perform therapeutic work without the risk of triggering an immune response or requiring immunosuppressants. They only last a few weeks before breaking down, and so can easily be re-absorbed into the body after their work is done.

In addition, outside of the body, Anthrobots can only survive in very specific laboratory conditions, and there is no risk of exposure or unintended spread outside the lab. Likewise, they do not reproduce, and they have no genetic edits, additions or deletions, so there is no risk of their evolving beyond existing safeguards.

How Are Anthrobots Made?

Each Anthrobot starts out as a single cell, derived from an adult donor. The cells come from the surface of the trachea and are covered with hairlike projections called cilia that wave back and forth. The cilia help the tracheal cells push out tiny particles that find their way into air passages of the lung.

We all experience the work of ciliated cells when we take the final step of expelling the particles and excess fluid by coughing or clearing our throats. Earlier studies by others had shown that when the cells are grown in the lab, they spontaneously form tiny multicellular spheres called organoids.

The researchers developed growth conditions that encouraged the cilia to face outward on organoids. Within a few days they started moving around, driven by the cilia acting like oars. They noted different shapes and types of movement the first. important feature observed of the biorobotics platform.

Levin says that if other features could be added to the Anthrobots (for example, contributed by different cells), they could be designed to respond to their environment, and travel to and perform functions in the body, or help build engineered tissues in the lab.

The team, with the help of Simon Garnier at the New Jersey Institute of Technology, characterized the different types of Anthrobots that were produced. They observed that bots fell into a few discrete categories of shape and movement, ranging in size from 30 to 500 micrometers (from the thickness of a human hair to the point of a sharpened pencil), filling an important niche between nanotechnology and larger engineered devices.

Some were spherical and fully covered in cilia, and some were irregular or football shaped with more patchy coverage of cilia, or just covered with cilia on one side. They traveled in straight lines, moved in tight circles, combined those movements, or just sat around and wiggled. The spherical ones fully covered with cilia tended to be wigglers.

The Anthrobots with cilia distributed unevenly tended to move forward for longer stretches in straight or curved paths. They usually survived about 45-60 days in laboratory conditions before they naturally biodegraded.

Anthrobots self-assemble in the lab dish, said Gumuskaya, who created the Anthrobots. Unlike Xenobots, they dont require tweezers or scalpels to give them shape, and we can use adult cells even cells from elderly patients instead of embryonic cells. Its fully scalablewe can produce swarms of these bots in parallel, which is a good start for developing a therapeutic tool.

LittleHealers

Because Levin and Gumuskaya ultimately plan to make Anthrobots with therapeutic applications, they created a lab test to see how the bots might heal wounds. The model involved growing a two-dimensional layer of human neurons, and simply by scratching the layer with a thin metal rod, they created an open wound devoid of cells.

To ensure the gap would be exposed to a dense concentration of Anthrobots, they created superbots a cluster that naturally forms when the Anthrobots are confined to a small space. The superbots were made up primarily of circlers and wigglers, so they would not wander too far away from the open wound.

Although it might be expected that genetic modifications of Anthrobot cells would be needed to help the bots encourage neural growth, surprisingly the unmodified Anthrobots triggered substantial regrowth, creating a bridge of neurons as thick as the rest of the healthy cells on the plate.

Neurons did not grow in the wound where Anthrobots were absent. At least in the simplified 2D world of the lab dish, the Anthrobot assemblies encouraged efficient healing of live neural tissue.

According to the researchers, further development of the bots could lead to other applications, including clearing plaque buildup in the arteries of atherosclerosis patients, repairing spinal cord or retinal nerve damage, recognizing bacteria or cancer cells, or delivering drugs to targeted tissues. The Anthrobots could in theory assist in healing tissues, while also laying down pro-regenerative drugs.

Making New Blueprints, Restoring Old Ones

Gumuskaya explained that cells have the innate ability to self-assemble into larger structures in certain fundamental ways.

The cells can form layers, fold, make spheres, sort and separate themselves by type, fuse together, or even move, Gumuskaya said.

Two important differences from inanimate bricks are that cells can communicate with each other and create these structures dynamically, and each cell is programmed with many functions, like movement, secretion of molecules, detection of signals and more. We are just figuring out how to combine these elements to create new biological body plans and functionsdifferent than those found in nature.

Taking advantage of the inherently flexible rules of cellular assembly helps the scientists construct the bots, but it can also help them understand how natural body plans assemble, how the genome and environment work together to create tissues, organs, and limbs, and how to restore them withregenerative treatments.

Author: Mike Silver Source: Tufts University Contact: Mike Silver Tufts University Image: The image is credited to Gizem Gumuskaya, Tufts University

Original Research: Open access. Motile Living Biobots Self-Construct from Adult Human Somatic Progenitor Seed Cells by Michael Levin et al. Advanced Science

Abstract

Motile Living Biobots Self-Construct from Adult Human Somatic Progenitor Seed Cells

Fundamental knowledge gaps exist about the plasticity of cells from adult soma and the potential diversity of body shape and behavior in living constructs derived from genetically wild-type cells.

Here anthrobots are introduced, a spheroid-shaped multicellular biological robot (biobot) platform with diameters ranging from 30 to 500microns and cilia-powered locomotive abilities.

Each Anthrobot begins as a single cell, derived from the adult human lung, and self-constructs into a multicellular motile biobot after being cultured in extra cellular matrix for 2 weeks and transferred into a minimally viscous habitat.

Anthrobots exhibit diverse behaviors with motility patterns ranging from tight loops to straight lines and speeds ranging from 550micronss1. The anatomical investigations reveal that this behavioral diversity is significantly correlated with their morphological diversity.

Anthrobots can assume morphologies with fully polarized or wholly ciliated bodies and spherical or ellipsoidal shapes, each related to a distinct movement type. Anthrobots are found to be capable of traversing, andinducing rapid repair of scratches in, cultured human neural cell sheets in vitro.

By controlling microenvironmental cues in bulk, novel structures, with new and unexpected behavior and biomedically-relevant capabilities, can be discovered in morphogenetic processes without direct genetic editing or manual sculpting.

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Anthrobots: Tiny Biobots From Human Cells Heal Neurons - Neuroscience News

Neuroscience

Neuroscience and Neurology: New Insights into Neurodegenerative Diseases – Medriva

Recent findings in neuroscience and neurology have started to shed light on the intricate connections between personality traits, dementia diagnoses, Parkinsons disease, and multiple sclerosis. These understandings not only contribute to the scientific communitys growing knowledge of these complex conditions but also potentially pave the way for innovative treatment options.

A recent meta-analysis revealed that personality traits are strong predictors of dementia diagnoses. However, the association between these traits and neuropathology at autopsy was not consistently found. This suggests that while personality traits may help predict the risk of dementia, they may not directly correlate with the physical manifestations of the disease in the brain.

Another significant finding is that neuronally derived extracellular vesicle-associated alpha-synuclein in serum correctly identified 80% of at-risk individuals who phenoconverted to Parkinsons disease and related dementia. This discovery suggests that this biomarker could be instrumental in identifying individuals at risk of developing Parkinsons disease and related dementia.

Groundbreaking treatment approaches are also being explored. High-dose nicotinamide riboside, a form of vitamin B3, showed promise in easing Parkinsons motor symptoms in a phase I trial. Additionally, a phase I study demonstrated the tolerability of injecting allogeneic neural stem cells into the brains of people with secondary progressive multiple sclerosis, suggesting potential new therapeutic approaches for these neurodegenerative diseases.

Another area of recent research has focused on the link between blood-based biomarkers of amyloid, tau, and neurodegeneration and domain-specific neuropsychological performance in women with and without HIV. The results could have significant implications for understanding cognitive impairment in both the general population and those living with HIV.

The role of the TREM2 protein in neurodegeneration has also been a focus of recent research. Specifically, a mutation in this protein may promote synapse loss in mice, contributing to cognitive decline. Furthermore, salty immune cells surrounding the brain were associated with hypertension-induced dementia in mice, suggesting a possible link between dietary salt intake, hypertension, and dementia.

Finally, a Norwegian study found a moderate association between objectively measured hearing impairment and dementia in people aged 70 to 85. This correlation underlines the importance of early detection and intervention in hearing impairment to potentially reduce the risk of dementia.

In conclusion, these developments in neuroscience and neurology are expanding our understanding of neurodegenerative diseases and offering new avenues for potential treatments. The ongoing research in this field continues to bring hope for those affected by these conditions and their families.

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Neuroscience and Neurology: New Insights into Neurodegenerative Diseases - Medriva

Neuroscience

How Imagination Fuels Empathy and Prosocial Behavior – Neuroscience News

Summary: A new study highlights the significant role of imagination in evoking empathy and driving prosocial behavior. While empathy is multifaceted, this research focuses on two aspects: personal distress and compassionate concern.

The study reveals that vividly imagining someone elses problems increases personal distress, motivating individuals to offer help.

These findings break new ground in understanding the connection between mental experiences and actions, shedding light on why certain situations and individuals elicit more empathy than others.

Key Facts:

Source: McGill University

In a world grappling with deep-seated division and social upheaval, empathy has become more critical than ever.

But science suggests when it comes to evoking empathy, our imagination is more powerful than we previously thought. A new study, led by McGill researchers, reveals how the different ways to experience empathy affect our willingness to help others.

Empathy is the ability to understand the situation of another person and is vital for prosocial behaviours. However, we know that empathy isnt just one thing we can experience it very differently, either as personal distress or compassionate concern for that other person, explains McGill psychology professor Signy Sheldon, and the studys co-author.

Until now, research in empathy has largely focused on how imagining helping another person can promote compassion, but not on how imagining another persons situation affects empathy, which is usually our first mental course of action.

These findings, published inthe journalEmotionbreak new ground by showing how another form of empathy, personal distress, is more prominent when imagining those situations and may actually be a catalyst for taking action to help.

The joint effort between McGill and Albany University discovered that when we vividly imagine someone elses problems in our minds, it makes us feel their pain more and motivates us to lend a helping hand.

The findings bring us closer to cracking the code of human behaviour and the link between our mental experiences and prosocial actions. These results are important for understanding why some situations and even people seem more empathetic than others.

If you hear your friend has lost a loved one or a neighbors car was stolen, what happens in your mind? Do you take on the pain of your friend or do you feel concern and compassion?

The research involved three online experiments where participants were asked to truly visualize themselves in another persons shoes.

Our experiments revealed that when people simulated distressful scenarios of other individuals, they felt much more personal distress than when these scenarios were not simulated. Interestingly, we also found imagining these scenarios in such a way increased the willingness to help that individual, says Sheldon, Canada Research Chair in Cognitive Neuroscience of Memory.

As imagining others situations is linked to episodic memory, this discovery raises significant questions about the link between memory capacity and empathy, which is an important avenue for further research.

Author: Keila DePape Source: McGill University Contact: Keila DePape McGill University Image: The image is credited to Neuroscience News

Original Research: Closed access. From memory to motivation: Probing the relationship between episodic simulation, empathy, and helping intentions by Signy Sheldon et al. Emotion

Abstract

From memory to motivation: Probing the relationship between episodic simulation, empathy, and helping intentions

Research has documented a strong link between constructingepisodic simulationsvivid imaginations of specific eventsand empathy. To date, most studies have used episodic simulations of helping someone to facilitate affective empathy and promote helping intentions, but have not studied how episodic simulations of anothers distressing situation affect empathy.

Moreover, affective empathy encompasses bothpersonal distress(i.e., an egocentric experience of distress in response to anothers circumstances) and empathic concern (i.e., compassion for another), but we do not know how episodic simulations affect each component.

To address these questions, we ran three experiments testing how different episodic simulations influenced personal distress and empathic concern, and thereby willingness to help.

In Experiment 1 (N= 216), we found that participants who constructed episodic simulations of anothers situation reported increased personal distress (but not empathic concern) and increased helping intentions compared to a control group; additional analyses revealed that personal distress mediated the simulation effect on helping.

Furthermore, in Experiment 2 (N= 213), we contrasted episodic simulation of helping versus the distressing scenario; we found no differences in personal distress or helping intentions, but simulating helping led to higher empathic concern.

Experiment 3 (N= 571) included both simulation conditions and a control condition; we fully replicated our findings, additionally showing that simulating a helping interaction increased personal distress, empathic concern, and helping intentions relative to the control condition, which consisted of prior work.

Taken together, our work illustrates how distinct forms of episodic simulation differentially guide empathic responding and highlights the importance of personal distress in motivating helping.

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How Imagination Fuels Empathy and Prosocial Behavior - Neuroscience News

Neuroscience

Peptide PACAP’s Key Role in Alcohol Addiction – Neuroscience News

Summary: Alcohol, the worlds most common addictive substance, leads to $249 billion in annual costs and 88,000 deaths in the U.S. Alcohol use disorder affects millions but is under-treated.

Researchers discovered a key player in alcohol addiction: pituitary adenylate cyclase activating polypeptide (PACAP). This peptide, found in the bed nucleus of the stria terminalis (BNST), is linked to heavy alcohol drinking and withdrawal.

Inhibiting PACAP in the BNST significantly reduces alcohol consumption, offering a potential target for novel treatments.

Key Facts:

Source: Boston University

Alcohol is the most common addictive substance in the world. Every year in the U.S. excessive alcohol use costs $249 billion and causes approximately 88,000 deaths, as well as various chronic diseases and social issues.

Alcohol use disorder, a highly prevalent, chronic, relapsing disorder, affects more than 14 million people in the U.S. alone, in addition to being severely under-treated, with only three modestly effective pharmacological therapies available.

Chronic exposure to alcohol has been shown to produce profound neuroadaptations in specific brain regions, including the recruitment of key stress neurotransmitters, ultimately causing changes in the body that sustain excessive drinking. The area of the brain known as the bed nucleus of the stria terminalis (BNST) is critically involved in the behavioral response to stress as well as in chronic, pathological alcohol use.

Researchers from Boston University Chobanian & Avedisian School of Medicine have identified that a peptide called pituitary adenylate cyclase activating polypeptide (PACAP), is involved in heavy alcohol drinking. In addition, they have discovered that this peptide acts in the BNST area.

Using an established experimental model for heavy, intermittent alcohol drinking, the researchers observed that during withdrawal this model showed increased levels of the stress neuropeptide PACAP selectively in the BNST, compared to the control model.

Interestingly, a similar increase was also observed in the levels of another stress neuropeptide closely related to PACAP, the calcitonin gene-related peptide, or CGRP. Both peptides have been implicated in stress as well as pain sensitivity, but their role in alcohol addiction is less established.

The researchers then used a virus in a transgenic model to block the neural pathways containing PACAP that specifically arrive to the BNST. We found that inhibiting PACAP to the BNST dramatically reduced heavy ethanol drinking, explained co-corresponding author Valentina Sabino, PhD, co-director of the Schools Laboratory of Addictive Disorders as well as professor of pharmacology, physiology & biophysics.

According to the researchers, these results provide evidence that this protein mediates the addictive properties of alcohol. We found a key player, PACAP, driving heavy alcohol drinking, which can be targeted for the development of novel pharmacological therapies, added co-corresponding author Pietro Cottone, PhD, associate professor of pharmacology, physiology & biophysics and co-director of the Laboratory of Addictive Disorders.

These findings appear online in the journaleNeuro.

Funding: Funding for this study was to grants number AA026051 (PC), AA025038 (VS), and AA024439 (VS) from the National Institute on Alcohol and Alcoholism (NIAAA), the Boston University Undergraduate Research Opportunities Program (UROP), the Boston University Micro and Nano Imaging Facility and the Office of the Director of the National Institutes of Health (S10OD024993).

Author: Gina DiGravio Source: Boston University Contact: Gina DiGravio Boston University Image: The image is credited to Neuroscience News

Original Research: Closed access. Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking in Mice by Valentina Sabino et al. eNeuro

Abstract

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking in Mice

Alcohol use disorder (AUD) is a complex psychiatric disease characterized by periods of heavy drinking and periods of withdrawal. Chronic exposure to ethanol causes profound neuroadaptations in the extended amygdala, which cause allostatic changes promoting excessive drinking.

The bed nucleus of the stria terminalis (BNST), a brain region involved in both excessive drinking and anxiety-like behavior, shows particularly high levels of pituitary adenylate cyclase activating polypeptide (PACAP), a key mediator of the stress response.

Recently, a role for PACAP in withdrawal-induced alcohol drinking and anxiety-like behavior in alcohol-dependent rats has been proposed; whether the PACAP system of the BNST is also recruited in other models of alcohol addiction and whether it is of local or non-local origin is currently unknown.

Here, we show that PACAP immunoreactivity is increased selectively in the BNST of C57Bl/6J mice exposed to a chronic, intermittent access to ethanol.

While PAC1R expressing cells were unchanged by chronic alcohol, the levels of a peptide closely related to PACAP, the calcitonin gene related neuropeptide (CGRP), were found to also be increased in the BNST.

Finally, using a retrograde chemogenetic approach in PACAP-ires-Cre mice, we found that the inhibition of PACAP neuronal afferents to the BNST reduced heavy ethanol drinking.

Our data suggest that the PACAP system of the BNST is recruited by chronic, voluntary alcohol drinking in mice and that non-locally originating PACAP projections to the BNST regulate heavy alcohol intake, indicating that this system may represent a promising target for novel AUD therapies.

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Peptide PACAP's Key Role in Alcohol Addiction - Neuroscience News

Neuroscience

Fruit Fly Study Sheds Light on Aggression’s Neural Roots – Neuroscience News

Summary: Researchers have discovered new insights into persistent aggression in female fruit flies, challenging existing theories.

A new study shows that certain neural cells sustain aggressive behavior for up to 10 minutes, suggesting factors beyond recurrent neural connections are at play.

These findings could aid understanding of human aggression and related neurological conditions, highlighting the need for revised models of aggression in the brain.

Key Facts:

Source: HHMI

Its one of those days. On the drive home from work, the car in the next lane cuts you off. You slam on the brakes, lay on the horn, and yell choice words at the offending driver. When you walk into your house half an hour later, youre still angry, and snap at your partner when they ask about your day.

Fruit flies may not have to worry about the lingering effects of road rage, but they also experience states of persistent aggression. In the case of female fruit flies, this behavior is a survival mechanism, causing the flies to headbutt, shove, and fence other female fruit flies to guard prime egg-laying territory on a ripe banana.

Now, researchers at Janelia and the California Institute of Technology are homing in on the neurons, circuits, and mechanisms responsible for this tenacious behavior.

In anew study, the researchers report theyve teased out the cell types contributing to a persistent aggressive state in female fruit flies, showing that some cells associated with aggression can cause flies to remain angry for up to 10 minutes.

They also found that this persistent state may not be solely due to a recurrent connection between the aggression-associated cells, as had been thought. In a recurrent connection, signals loop back and feed into the same neural circuit, which could cause a behavior to persist.

Instead, the new research suggests persistent aggression could be regulated by other factors, including neuromodulators affecting neuronal activity, neurons downstream from the aggression-associated cells, or other circuits in the fly brain. Considering their findings, scientists may need to develop a new model that considers these other factors in addition to recurrent connections to explain this enduring behavior.

It is interesting for the field because we talk about these recurrent connections as being key for the persistent state, and thats really what we thought, says Katie Schretter, a postdoc in the Rubin Lab who led the research. But now it seems less clear in this case.

Understanding persistent internal states like aggression could help researchers better uncover how the brain makes decisions for instance, whether to stay mad or move on and the individual circuits involved in these choices. Figuring out the underlying mechanisms behind aggression could also help scientists better understand aggressive behavior in humans, including behaviors that can occur alongside neurodegenerative or psychiatric diseases.

For our society, its important to be able to decrease aggression and figure out how to stop persistent aggression, Schretter says. Figuring out how the circuit works can help us figure out how we might decrease it.

Fighting fruit flies

Scientists had previously identified cell types associated with aggression in the brains of female fruit flies. They found that activating these cells caused the flies to fight. Given this, the team, led by Schretter, Cal Tech graduate student Hui (Vivian) Chiu, Janelia Senior Group Leader Gerry Rubin, and HHMI Investigator David Anderson, wanted to look at these cells to see how their signals might feed back into each other to generate a persistent aggressive state.

The researchers separated female flies with a barrier and then activated the different cell types associated with aggression for 30 seconds at a time. They kept the flies separated for specific periods of time, up to 30 minutes, before removing the barrier and letting them interact.

The team hypothesized that recurrent connections between certain aggression-associated cell types could cause the flies to remain aggressive for longer periods of time.

They found that one cell type associated with aggression aIPg contributes to persistent aggression. When these cells were activated, the flies would fight for up to 10 minutes after the barrier was removed. But another cell type previously found to be involved in aggression pC1d did not cause this same enduring anger.

pC1d also didnt affect whether aIPg caused persistent aggression, and neither pC1d nor aIPg showed persistent neuronal activity. These findings suggest that a persistent aggressive state doesnt depend on a recurrent connection between the two cell types.

Previous research had shown that stimulating another cell associated with aggression pC1e also does not cause persistent behavior on its own. However, Schretter and colleagues were surprised to find that when pC1d and pC1e were stimulated simultaneously, the flies remained persistently aggressive.

Taken together, the results suggest that the persistent aggressive state may be maintained by a mechanism different from what the researchers had originally thought. Instead of being due to a recurrent connection between aIPg and pC1d, as they had hypothesized, persistent aggression could involve pC1e.

But it could also include other factors, such as a neuromodulator acting on the circuit or the effect of neurons downstream from aIPg, pC1d, and pC1e. Or aggression could be controlled by another circuit altogether.

Schretter says investigating these other models to explain persistent aggression is the next step.

Its exciting to see what else could lengthen that persistence, because there could be other circuits that are also involved, she says. It is basically open for us to go after, so it is a fun place to be.

Author: Nanci Bompey Source: HHMI Contact: Nanci Bompey HHMI Image: The image is credited to the CDC and is in the public domain

Original Research: Open access. Cell type-specific contributions to a persistent aggressive internal state in femaleDrosophila by Katie Schretter et al. eLife

Abstract

Cell type-specific contributions to a persistent aggressive internal state in femaleDrosophila

Persistent internal states are important for maintaining survival-promoting behaviors, such as aggression. In femaleDrosophila melanogaster, we have previously shown that individually activating either aIPg or pC1d cell types can induce aggression.

Here we investigate further the individual roles of these cholinergic, sexually dimorphic cell types, and the reciprocal connections between them, in generating a persistent aggressive internal state.

We find that a brief 30-second optogenetic stimulation of aIPg neurons was sufficient to promote an aggressive internal state lasting at least 10 minutes, whereas similar stimulation of pC1d neurons did not.

While we previously showed that stimulation of pC1e alone does not evoke aggression, persistent behavior could be promoted through simultaneous stimulation of pC1d and pC1e, suggesting an unexpected synergy of these cell types in establishing a persistent aggressive state.

Neither aIPg nor pC1d show persistent neuronal activity themselves, implying that the persistent internal state is maintained by other mechanisms.

Moreover, inactivation of pC1d did not significantly reduce aIPg-evoked persistent aggression arguing that the aggressive state did not depend on pC1d-aIPg recurrent connectivity.

Our results suggest the need for alternative models to explain persistent female aggression.

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Fruit Fly Study Sheds Light on Aggression's Neural Roots - Neuroscience News

Neuroscience

Two leading standards bodies launch Neuroscience Community, powering a global data network that will speed up … – EurekAlert

image:

GA4GH & INCF launch Neuroscience Community

Credit: Global Alliance for Genomics and Health / Stephanie Li

The Global Alliance for Genomics and Health (GA4GH) and the International Neuroinformatics Coordinating Facility (INCF) launched a new group to lay the groundwork for connecting global neuroscience and genomic data.

Answering data-driven questions in neuroscience means dealing with complexity: in types of data, data management systems, the number and variety of conditions, ethical and legal requirements, and the genetic and biological conditions themselves. Even just aligning industry standards for neuroimaging and genomics can be a struggle.

To improve life for people with neurological conditions, we need to tackle the complexity together.

The newGA4GH & INCF Neuroscience Communityunites collaborators from around the world to share best practices and improve standards that will expand responsible use of neuroscientific data, including genomic data. Interested organisations canjoin today.

A parent wants to understand why their autistic five-year-old wakes up multiple times a night, but doctors cant explain. A person with early-onset Parkinsons struggles to find a cocktail of medications that wards off the symptoms but doesnt make them sleepy, irritable, and confused on the job. Someone has tried every treatment for severe depression that their insurance will pay for, but nothing works.

For people with neurological conditions and their families, the healthcare system can seem to offer more headache than help.

Those with illnesses like Parkinsons, addiction, depression, and epilepsy often report worse quality of life than others. So domany neurodivergent people, including autistic people and those with ADHD.For example, people with epilepsy are at greater risk ofdying early. Many autistic children facegastrointestinalandsleepproblems.

Progress has been slow to tailor healthcare for neurodivergent people and neurological patients. In part, thats because researchers need lots and lots of data and many differenttypesof data to answer neuroscience questions.

To fully understand just one neurological patient or research participant, you need brain images, genomic sequences, gene expression data, socio-cultural factors, test results showing how they metabolise drugs, their overall health history and their familys, and biomarker data like health and weight. Then add a detailed work-up of their phenotype, or the traits, behaviours, and symptoms they show, said neuroscientist Randy McIntosh, Co-Lead of the GA4GH & INCF Neuroscience Community, Deputy Chair of the INCF Governing Board, and professor at Simon Fraser University.

Now multiply that amount of data by thousands of people, which you need to get real predictive power in a study, he said.

A single organisation is unlikely to collect or manage so much data. Yet sharing data between groups is difficult, in part for an important reason: stewarding someones data means taking great care to protect their privacy, wishes, and legal rights.

One solution is data visiting.

Instead of downloading a data file and transferring it to a faraway scientist, data visiting means that a scientist visits the data where it lives. These days, data visiting is done virtually: algorithms or other computer tools travel to an institutions trove of data, or a secure environment where many institutions share their data, and run tests. Then they send the results to scientists with proper access permissions.

To visit the most data possible, you need a federated network where you can study data housed in many different locations, all at once.

No matter your access method, you need to use data responsibly. Groups like the Wellcome-funded Brain Research International Data Governance & Exchange Program (BRIDGE) a Neuroscience Community member are studying how to properly follow laws and regulations when making data available worldwide. BRIDGE works with partners in Brazil, the US, South Africa, Switzerland, and the UK to develop resources for governing neuroscience data.

Conditions and diseases dont respect borders. If we want the lives of people with neurological conditions to improve, we cant just look at data from one hospital or even one country. We have to study diverse data from around the world. With data visiting powered by federation and Global Alliance for Genomics and Health standards, clinicians and researchers can vastly expand their pool of data while data stewards rest easy knowing they are protecting rights and following regulations, said Peter Goodhand, CEO of GA4GH.

The GA4GH & INCF Neuroscience Community will connect international partners to develop the standards, collaborations, and systems needed to power data visiting across a global network.

The community will help get answers faster for patients and people everywhere, while respecting the human rights of people who donate their data. (Read the communitysin-progress charter.)

For nearly two decades, INCF has developed standards and best practices to make neuroscience data FAIR: findable, accessible, interoperable, and reusable. Now we are eager to work with partners from genomics, like GA4GH, to ensure that our standards development efforts progress together and lead to the best possible science, said Mathew Abrams, Director of Science and Training for INCF.

The GA4GH & INCF Neuroscience Community will expand neuroscience and genomic data networking around the world ramping up what many members are already doing.

In Ontario, Canada, for example, several Neuroscience Community members run projects to link data across the province and the globe.

Take software company DNAstack. Working closely with the Autism Sharing Initiative (a GA4GH Driver Project), the company developed the Neuroscience AI network with its existing Omics AI software. The network makes it easier to find, analyse, and apply artificial intelligence to autism and other neuroscience datasets.

Then Azadeh Kushki, a researcher at Holland Bloorview Kids Rehabilitation Hospital also a Neuroscience Community member arrived. She used Neuroscience AI to make an important discovery: neurodivergent kids might be prescribed medication differently based on their ethnicity and family income.

The finding relied on a machine learning model trained on a federated network that follows GA4GH standards. Thanks to the Neuroscience Community, other groups will learn how to apply this powerful technique.

Another Neuroscience Community member, the Ontario Brain Institute, scaled up even further. Its Brain-CODE platform includes not only neurodevelopmental but also concussion, mental health, cerebral palsy, epilepsy, and neurodegenerative data. Brain-CODE houses data from more than 20,000 people who agreed to give researchers and other third parties access.

For more than 10 years, the Ontario Brain Institute has fostered an integrated approach for neuroscience discovery to improve brain health. By combining ideas and expertise from patients, researchers, and industry, weve created a powerful ecosystem of innovation using data, analytics, and AI. But we cant do this alone. With the GA4GH & INCF Neuroscience Community, we have a genuinely international opportunity to combine efforts and reach breakthroughs faster, said Francis Jeanson, Head of the Centre for Analytics at Ontario Brain Institute and Co-Lead of the GA4GH & INCF Neuroscience Community.

The new Neuroscience Community is one of severalCommunities of Interestfounded in recent years by GA4GH. These groups bring together global experts who focus on a specific topic, and who are eager to connect across borders and find a path to better data use.

Great work is happening all over the world to understand neurological conditions, including their genomic underpinnings. The GA4GH & INCF Neuroscience Community will ensure that all those experts are sharing best practices, developing interoperable standards, and building connections across data, said Angela Page, GA4GH Director of Strategy and Engagement. People with neurological conditions have advocated for and deserve a global data network that will lead to better healthcare and improved quality of life.

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About GA4GH

The Global Alliance for Genomics and Health (GA4GH) is an international, not-for-profit alliance formed in 2013 to accelerate progress in human health by expanding responsible use of genomic data. Bringing together 500+ leading organisations working in healthcare, research, patient advocacy, life science, and information technology, the GA4GH community creates frameworks and standards that power the responsible, broad, and democratised use of genomic and related health data.

About INCF

The International Neuroinformatics Coordinating Facility (INCF) network serves as a forum to collaboratively coordinate global neuroinformatics activities that guide and oversee the development of standards, best practices, ontologies, and other unifying activities. The mission of INCF network is to promote the uptake of FAIR data management practices in neuroscience through the development of standards and best practices that support open, FAIR, and citable neuroscience. INCF also provides training on how standards and best practices facilitate reproducibility and enables the publishing of the entirety of research output, including data and code.

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Two leading standards bodies launch Neuroscience Community, powering a global data network that will speed up ... - EurekAlert

Neuroscience

Personality Predictors of Dementia; Parkinson’s Blood Test; Klotho in Alzheimer’s – Medpage Today

Personality traits were strong predictors of dementia diagnoses in a meta-analysis, but were not consistently associated with neuropathology at autopsy. (Alzheimer's and Dementia)

Neuronally derived extracellular vesicle-associated alpha-synuclein in serum correctly identified 80% of at-risk people who phenoconverted to Parkinson's disease and related dementia. (JAMA Neurology)

High-dose nicotinamide riboside eased Parkinson's motor symptoms in a phase I trial. (Nature Communications)

Injecting allogeneic neural stem cells into the brains of people with secondary progressive multiple sclerosis was tolerated in a phase I study. (Cell Stem Cell)

Klotho protein levels differed in clinical stages of Alzheimer's and were associated with amyloid and tau burden. (JAMA Network Open)

Newborn infants perceived the beat in music. (Cognition)

Short sleep and sleep variability were linked with impaired cognitive performance in older adults. (JAMA Network Open)

Liver fibrosis was associated with cognitive decline in Parkinson's disease. (Journal of Clinical Neuroscience)

Blood-based biomarkers of amyloid, tau, and neurodegeneration were tied to domain-specific neuropsychological performance in women with and without HIV. (JAMA Network Open)

Microglia with the R47H/+ mutation in TREM2 protein promoted synapse loss in mice. (GLIA)

Also in mice, salty immune cells that surrounded the brain were linked with hypertension-induced dementia. (Nature Neuroscience)

A Norwegian study found a moderate association between objectively measured hearing impairment and dementia in people ages 70 to 85. (eClinicalMedicine)

Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimers, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinsons, ALS, concussion, CTE, sleep, pain, and more. Follow

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Personality Predictors of Dementia; Parkinson's Blood Test; Klotho in Alzheimer's - Medpage Today

Neuroscience

RNA’s Pivotal Role in Fear Memory and PTSD Treatment – Neuroscience News

Summary: Researchers have revealed a groundbreaking role of RNA in fear-related learning and memory. Their study shows how noncoding RNA Gas5 influences neuronal excitability, impacting learning and memory processes.

Another study identified m6A-modified RNAs that regulate synaptic plasticity, crucial for fear extinction memory, a key factor in PTSD. These findings offer new insights into RNAs role in the brain and potential RNA-based therapies for PTSD.

Key Facts:

Source: University of Queensland

Researchers fromThe University of Queenslandhave discovered a new way ribonucleic acid (RNA) impacts fear-related learning and memory.

Professor Timothy BredyfromUQs Queensland Brain Institutesaid this is an exciting example of RNAs role in fine-tuning the cellular functions in the brain.

In a paper published inNature Communications, researchers demonstrated that a noncoding RNA known as Gas5 coordinates the trafficking and clustering of RNA molecules inside the long processes of neurons, and orchestrating neuronal excitability in real time that contributes to learning and memory.

Understanding the complex world of RNA is a rapidly emerging area of neuroscience research, where we are constantly learning more about how different classes of RNA control the communication between and within brain cells, Professor Bredy said.

In this study, we found learning-related RNAs at the synapse and one, in particular, called Gas5 seems to be uniquely required for fear extinction memory.

Theres a lot more happening with these kinds of RNA molecules than we first thought and that fact they influence cellular function on a millisecond timeframe, which mirrors the real time changes in synaptic function that happen in the brain during learning, is extraordinary.

Non-coding RNA may be the missing link to understanding how the brain processes critically important inputs that lead to the formation of memory

This study builds on earlier findings this year from the Bredy Lab which identified a separate population of learning-related RNAs that accumulate near the synapse the junction between neurons that allow them to communicate.

In that paper, published in theJournal of Neuroscience, they uncovered several new synapse-specific RNA that harbour a specific chemical tag called N6-methyladenosine (m6A).

Lead authorDr Sachithrani Madugallesaid the findings highlighted the importance of m6A-modified RNAs in regulating synaptic plasticity.

Readers are proteins that bind to the chemical tag and direct it to locations and functions, Dr Madugalle said.

The readers allowed us to determine the functional role of m6A-modified RNA molecules in the formation of new memories.

By examining one such RNA, Malat1, we discovered the key proteins that interact with this RNA and support processes related to an important type of memory called fear extinction.

Fear extinction impairment is associated with post-traumatic stress disorder (PTSD).

When Malat1 is chemically decorated with m6A, this allows it to interact with different proteins in the synaptic compartment, which can then alter the mechanisms involved in the formation of fear extinction memory.

This new information may inform the development of future RNA therapies to address PTSD.

By understanding where, when, and how an RNA molecule is activated and having a precise marker will help us identify the target for therapies.

In addition, in both studies the team employed an innovative new tool that allowed them to manipulate the functional state of an RNA molecule, together with Professor Bryan Dickinson and Dr. Simone Rauch at the University of Chicago.

We are now looking for ways to harness RNA to control the aspects of synaptic function underlying memory formation and to potentially develop an RNA therapeutic for the treatment of PTSD and phobia, Professor Bredy said.

Author: Lisa Clarke Source: University of Queensland Contact: Lisa Clarke University of Queensland Image: The image is credited to Neuroscience News

Original Research: Open access. Fear extinction is regulated by the activity of long noncoding RNAs at the synapse by Sachithrani Madugalle et al. Nature Communications

Closed access. Synapse-Enriched m6A-Modified Malat1 Interacts with the Novel m6A Reader, DPYSL2, and Is Required for Fear-Extinction Memory by Sachithrani Madugalle et al. Journal of Neuroscience

Abstract

Fear extinction is regulated by the activity of long noncoding RNAs at the synapse

Long noncoding RNAs (lncRNAs) represent a multidimensional class of regulatory molecules that are involved in many aspects of brain function.

Emerging evidence indicates that lncRNAs are localized to the synapse; however, a direct role for their activity in this subcellular compartment in memory formation has yet to be demonstrated.

Using lncRNA capture-seq, we identified a specific set of lncRNAs that accumulate in the synaptic compartment within the infralimbic prefrontal cortex of adult male C57/Bl6 mice.

Among these was a splice variant related to the stress-associated lncRNA,Gas5. RNA immunoprecipitation followed by mass spectrometry and single-molecule imaging revealed that thisGas5isoform, in association with the RNA binding proteins G3BP2 and CAPRIN1, regulates the activity-dependent trafficking and clustering of RNA granules.

In addition, we found that cell-type-specific, activity-dependent, and synapse-specific knockdown of theGas5variant led to impaired fear extinction memory.

These findings identify a new mechanism of fear extinction that involves the dynamic interaction between local lncRNA activity and RNA condensates in the synaptic compartment.

Abstract

Synapse-Enriched m6A-Modified Malat1 Interacts with the Novel m6A Reader, DPYSL2, and Is Required for Fear-Extinction Memory

The RNA modification N6-methyladenosine (m6A) regulates the interaction between RNA and various RNA binding proteins within the nucleus and other subcellular compartments and has recently been shown to be involved in experience-dependent plasticity, learning, and memory.

Using m6A RNA-sequencing, we have discovered a distinct population of learning-related m6A- modified RNAs at the synapse, which includes the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1). RNA immunoprecipitation and mass spectrometry revealed 12 new synapse-specific learning-induced m6A readers in the mPFC of male C57/BL6 mice, with m6A-modifiedMalat1binding to a subset of these, including CYFIP2 and DPYSL2.

In addition, a cell type- and synapse-specific, and state-dependent, reduction of m6A onMalat1impairs fear-extinction memory; an effect that likely occurs through a disruption in the interaction betweenMalat1and DPYSL2 and an associated decrease in dendritic spine formation.

These findings highlight the critical role of m6A in regulating the functional state of RNA during the consolidation of fear-extinction memory, and expand the repertoire of experience-dependent m6A readers in the synaptic compartment.

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RNA's Pivotal Role in Fear Memory and PTSD Treatment - Neuroscience News

Neuroscience

AI Reveals Brain Differences in ADHD – Neuroscience News

Summary: Researchers utilizing artificial intelligence (AI) to analyze brain MRI scans have identified significant differences in white matter tracts of adolescents with ADHD.

The study, involving over 1,700 participants from the multi-institutional Adolescent Brain Cognitive Development Study, used diffusion-weighted imaging (DWI) and a deep-learning AI model to detect these variations.

Elevated fractional anisotropy (FA) values were found in nine white matter tracts in individuals with ADHD, providing objective biomarkers for diagnosis. This approach offers a new, quantitative way to diagnose ADHD, addressing the current reliance on subjective self-reported surveys.

Key Facts:

Source: RSNA

Using artificial intelligence (AI) to analyze specialized brain MRI scans of adolescents with and without attention-deficit/hyperactivity disorder (ADHD), researchers found significant differences in nine brain white matter tracts in individuals with ADHD. Results of the study will be presented today at theannual meetingof the Radiological Society of North America (RSNA).

ADHD is a common disorder often diagnosed in childhood and continuing into adulthood, according to the Centers for Disease Control and Prevention. In the U.S., an estimated 5.7 million children and adolescents between the ages of 6 and 17 have been diagnosed with ADHD.

ADHD often manifests at an early age and can have a massive impact on someones quality of life and ability to function in society, said study co-author Justin Huynh, M.S., a research specialist in the Department of Neuroradiology at the University of California, San Francisco, and medical student at the Carle Illinois College of Medicine at Urbana-Champaign.

It is also becoming increasingly prevalent in society among todays youth, with the influx of smartphones and other distracting devices readily accessible.

Children with ADHD may have trouble paying attention, controlling impulsive behaviors or regulating activity. Early diagnosis and intervention are key to managing the condition.

ADHD is extremely difficult to diagnose and relies on subjective self-reported surveys, Huynh said. There is definitely an unmet need for more objective metrics for diagnosis. Thats the gap we are trying to fill.

Huynh said this is the first study to apply deep learning, a type of AI, to identify markers of ADHD in the multi-institutional Adolescent Brain Cognitive Development (ABCD) Study, which includes brain imaging, clinical surveys and other data on over 11,000 adolescents from 21 research sites in the U.S. The brain imaging data included a specialized type of MRI called diffusion-weighted imaging (DWI).

Prior research studies using AI to detect ADHD have not been successful due to a small sample size and the complexity of the disorder, Huynh said.

The research team selected a group of 1,704 individuals from the ABCD dataset, including adolescents with and without ADHD. Using DWI scans, the researchers extracted fractional anisotropy (FA) measurements along 30 major white matter tracts in the brain. FA is a measure of how water molecules move along the fibers of white matter tracts.

The FA values from 1,371 individuals were used as input for training a deep-learning AI model, which was then tested on 333 patients, including 193 diagnosed with ADHD and 140 without. ADHD diagnoses were determined by the Brief Problem Monitor assessment, a rating tool used for monitoring a childs functioning and their responses to interventions.

With the help of AI, the researchers discovered that in patients with ADHD, FA values were significantly elevated in nine white matter tracts.

These differences in MRI signatures in individuals with ADHD have never been seen before at this level of detail, Huynh said. In general, the abnormalities seen in the nine white matter tracts coincide with the symptoms of ADHD.

The researchers intend to continue obtaining data from the rest of the individuals in the ABCD dataset, comparing the performance of additional AI models.

Many people feel that they have ADHD, but it is undiagnosed due to the subjective nature of the available diagnostic tests, Huynh said.

This method provides a promising step towards finding imaging biomarkers that can be used to diagnose ADHD in a quantitative, objective diagnostic framework, Huynh said.

Co-authors are Pierre F. Nedelec, M.S., M.T.M., Samuel Lashof-Regas, Michael Romano, M.D., Ph.D., Leo P. Sugrue, M.D., Ph.D., and Andreas M. Rauschecker, M.D., Ph.D.

Author: Linda Brooks Source: RSNA Contact: Linda Brooks RSNA Image: The image is credited to Neuroscience News

Original Research: The findings will be presented at the 109th Scientific Assembly and Annual Meeting of the Radiological Society of North America

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AI Reveals Brain Differences in ADHD - Neuroscience News

Neuroscience

Heartbeat’s Influence on Brain Activity – Neuroscience News

Summary: New research uncovered that the phases of a heartbeat significantly influence brain and motor system excitability.

The study utilized transcranial magnetic stimulation (TMS) on 37 healthy volunteers to observe changes in cortical and corticospinal excitability across the cardiac cycle. They found heightened excitability during the systolic phase, when blood vessels are distended.

This discovery could revolutionize treatments for depression and stroke by aligning them with the cardiac cycle for enhanced effectiveness.

Key Facts:

Source; PLOS

Optimal windows exist for action and perception during the 0.8 seconds of a heartbeat, according to research published November 28thin the open access journalPLOS Biology.

The sequence of contraction and relaxation is linked to changes in the motor system and its ability to respond to stimulation, and this could have implications for treatments for depression and stroke that excite nerve cells.

The ways in which we perceive and engage with the world are influenced by internal bodily processes such as heartbeats, respiration and digestion. Cardiac activity can influence auditory and visual perception, and touch and sensory perceptions have been shown to be impaired during the systolic phase of the cardiac cycle when blood vessels are briefly distended.

Esra Al of the Max Planck Institute for Human Cognitive and Brain Sciences,Germany, and colleagues, wanted to understand whether there were changes in cortical and corticospinal excitability the ability to respond to stimuli across the cardiac cycle. 37 healthy human volunteers aged between 18 and 40 years received a series of transcranial magnetic stimulation (TMS) pulses non-invasive short magnetic pulses that stimulate nerve cells above the right side of the brain.

Motor and cortical responses as well as heartbeats were measured during the pulses and the authors found that higher excitability was recorded during the systolic phase. These simultaneous recordings of brain activity, heart activity, and muscle activity, suggest the timing of heartbeats and their neural processing are linked to changes in the excitability of the motor system.

TMS is used in treatments for depression and recovery after stroke. The research raises questions about whether these could be fine-tuned to improve results, as well as contributing to a greater understanding of brain-body interactions in health and in disease.

The authors add, Intriguingly, this study uncovers a remarkable connection between the human heart and brain, revealing distinct time windows tailored for action and perception.

Author: Claire Turner Source: PLOS Contact: Claire Turner PLOS Image: The image is credited to Neuroscience News

Original Research: Open access. Cardiac activity impacts cortical motor excitability by Esra Al et al. PLoS Biology

Abstract

Cardiac activity impacts cortical motor excitability

Human cognition and action can be influenced by internal bodily processes such as heartbeats. For instance, somatosensory perception is impaired both during the systolic phase of the cardiac cycle and when heartbeats evoke stronger cortical responses.

Here, we test whether these cardiac effects originate from overall changes in cortical excitability.

Cortical and corticospinal excitability were assessed using electroencephalographic and electromyographic responses to transcranial magnetic stimulation while concurrently monitoring cardiac activity with electrocardiography.

Cortical and corticospinal excitability were found to be highest during systole and following stronger neural responses to heartbeats. Furthermore, in a motor task, handmuscle activity and the associated desynchronization of sensorimotor oscillations were stronger during systole.

These results suggest that systolic cardiac signals have a facilitatory effect on motor excitabilityin contrast to sensory attenuation that was previously reported for somatosensory perception. Thus, it is possible that distinct time windows exist across the cardiac cycle, optimizing either perception or action.

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Heartbeat's Influence on Brain Activity - Neuroscience News