Tag Archives: #brain

Learning Foreign Languages Can Affect The Processing Of Music in the Brain (Neuroscience)

Research has shown that a music-related hobby boosts language skills and affects the processing of speech in the brain. According to a new study, the reverse also happens – learning foreign languages can affect the processing of music in the brain.

Research Director Mari Tervaniemi from the University of Helsinki’s Faculty of Educational Sciences  investigated, in cooperation with researchers from the Beijing Normal University (BNU)  and the University of Turku, the link in the brain between language acquisition and music processing in Chinese elementary school pupils aged 8–11 by monitoring, for one school year, children who attended a music training programme and a similar programme for the English language. Brain responses associated with auditory processing were measured in the children before and after the programmes. Tervaniemi compared the results to those of children who attended other training programmes.

“The results demonstrated that both the music and the language programme had an impact on the neural processing of auditory signals,” Tervaniemi says. 

Learning achievements extend from language acquisition to music 

Surprisingly, attendance in the English training programme enhanced the processing of musically relevant sounds, particularly in terms of pitch processing. 

“A possible explanation for the finding is the language background of the children, as understanding Chinese, which is a tonal language, is largely based on the perception of pitch, which potentially equipped the study subjects with the ability to utilise precisely that trait when learning new things. That’s why attending the language training programme facilitated the early neural auditory processes more than the musical training.”

Tervaniemi says that the results support the notion that musical and linguistic brain functions are closely linked in the developing brain. Both music and language acquisition modulate auditory perception. However, whether they produce similar or different results in the developing brain of school-age children has not been systematically investigated in prior studies. 

At the beginning of the training programmes, the number of children studied using electroencephalogram (EEG) recordings was 120, of whom more than 80 also took part in EEG recordings a year later, after the programme.

In the music training, the children had the opportunity to sing a lot: they were taught to sing from both hand signs and sheet music. The language training programme emphasised the combination of spoken and written English, that is, simultaneous learning. At the same time, the English language employs an orthography that is different from Chinese. The one-hour programme sessions were held twice a week after school on school premises throughout the school year, with roughly 20 children and two teachers attending at a time. 

“In both programmes the children liked the content of the lessons which was very interactive and had many means to support communication between the children and the teacher” says Professor Sha Tao who led the study in Beijing. 

The article entitled Improved auditory functions caused by music versus foreign-language training at school age – is there a difference? was recently published in the esteemed Cerebral Cortex journal. 

Authors of the article: Tervaniemi, M., Putkinen, V., Nie, P., Wang, C., Du, B., Lu, J., Li, S., Cowley, B., Tammi, T., Tao, S. Cerebral Cortex. 

Featured image: Children attending the after school music club. (Image: Mari Tervaniemi)

Provided by University of Helsinki

Scientists Provide Molecular Insights Into Primate Hippocampal Aging (Neuroscience)

Deep inside our brain is a region called the hippocampus. It plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. But what drives it down the path of aging?

The hippocampus is a complex structure with a highly heterogeneous cell composition, so it is difficult to accurately reveal the molecular regulatory networks of various cell types contributing to the aging process with traditional techniques. In addition, due to the ethical restrictions, it is difficult to obtain disease-free human brain tissues of both young and old ages. All these factors have limited our understanding of the aging mechanism in the human hippocampus, let alone the development of therapeutic interventions.

Using brain tissues from non-human primates (NHPs), the ideal model to mimic human hippocampal aging, scientists from the Institute of Zoology of the Chinese Academy of Sciences and Xuanwu Hospital Capital Medical University have worked jointly and established the first single-nucleus transcriptomic landscape of primate hippocampal aging, revealed the molecular mechanism of its functional deterioration with age, and provided a valuable resource for the identification of new diagnostic biomarkers and potential therapeutic targets for interventions against hippocampal aging and related human neurodegenerative disorders. This study entitled “Single-nucleus transcriptomic landscape of primate hippocampal aging” is published online in Protein & Cell in 2021.

In this study, the aged NHP hippocampus was found to demonstrate an array of aging-associated damages, including genomic and epigenomic instability, loss of proteostasis, as well as increased inflammation. To explore unique cellular and molecular characteristics underlying these age-related phenotypes, scientists generated a high-resolution single-nucleus transcriptomic landscape of hippocampal aging in NHPs. This landscape is composed of the gene expression profiles of 12 major hippocampal cell types, including neural stem cells, transient amplified progenitor cells (TAPC), immature neurons, excitatory/inhibitory neurons, oligodendrocytes, and microglia. Among them, TAPC and microglia were most affected by aging, as they manifested the most aging-related differentially expressed genes and those annotated as high-risk genes for neurodegenerative diseases.

In-depth analysis of the dynamic gene-expression signatures of the stepwise neurogenesis trajectory revealed the impaired TAPC division and compromised neuronal function, underlying the early onset and later stage of dysregulation in adult hippocampal neurogenesis, respectively. This landscape also enabled the researchers to unveil contributing factors to a hostile microenvironment for neurogenesis in the aged hippocampus, namely the elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells. This may aggravate the loss of neurogenesis in the aged hippocampus, and may lead to the further decline of cognitive function and the occurrence of neurodegenerative diseases.

This study established, for the first time, a comprehensive single-nucleus transcriptomic atlas of primate hippocampal aging, which provides extensive resources for the illustration of age-related molecular signatures at the single-cell level, including changes of internal factors and external microenvironment that contribute collectively to the impaired ability for neuronal regeneration in the old hippocampus. It has deepened our understanding of age-related changes in hippocampal structure and function, and identified cell types and molecules that are most susceptible in the aging process of hippocampus, thus enabling the identification of potential diagnostic biomarkers and therapeutic targets for neurodegenerative diseases associated with hippocampal aging.

Featured image: Dangerous protein aggregates (Amyloid-beta) accumulate in the aged monkey hippocampus. Credit: Guanghui Liu, Institute of Zoology, Chinese Academy of Science

Reference: Hui Zhang et al, Single-nucleus transcriptomic landscape of primate hippocampal aging, Protein & Cell (2021). DOI: 10.1007/s13238-021-00852-9

Provided by Higher Education Press Limited

Mechanism That Triggers Brain Neurone Response Revealed (Neuroscience)

It is the first time it has been possible to see how neurotransmitters and proteins interact at the atomic level to trigger neuronal responses.

Researchers from the G-protein-coupled receptor-based drug development research group at the Hospital del Mar Medical Research Institute (IMIM) have been able to verify, with a degree of precision never before achieved, how the process that triggers the response of neurones in the brain occurs. This is an essential mechanism for understanding how moods or even processes such as addictions are produced, and in which neurotransmitters, molecules that help transmit information between neurones through specialised receptors, the G protein-coupled receptors (GPCRs), play a vital role.

Neurotransmission is one of the most crucial physiological processes, as its dysregulation can result in various neuropsychiatric disorders”, explains Dr. Jana Selent, principal author of the study, published in the journal Chemical Science, and coordinator of the research group that led the work. Very small changes in how information is transmitted by these molecules can trigger different reactions in the brain, some of which are linked to behaviour, addictions and moods.

Jana Selent and Tomasz Stepniewski © IMIM

Possible new treatments for psychiatric illnesses

Researchers have analysed how neurotransmitters connect to proteins in the cell membrane of neurones at the atomic level. They were able to determine which connections between the neurotransmitter and its receptor protein control how the cell will respond. They observed that evolution has naturally caused small changes in the regions where these connections occur, giving rise to different proteins capable of generating different cellular responses. This allows our body to regulate, in a very precise way, the response that the same neurotransmitter causes in the neurone and in the brain. With this information, the authors of the study were able to predict what would happen on each occasion by studying different types of proteins and modified neurotransmitters, checking their conclusions with cell experiments conducted in laboratories in Sweden and Canada.

In this way, the researchers were able to relate the small differences that receptors in these important regions may have to the neuronal response they generate when interacting with the same neurotransmitter. It also shows how modified neurotransmitters can control which regions of the protein they can bind to, to be able to cause a different neuronal response. This makes it possible to “design molecules that only bind to certain regions of the receptor and to specific types of receptors, which may allow the neuronal response to be changed”, explains Dr Tomasz Stepniewski, first author of the study. This possibility is “particularly interesting in neuropsychiatric diseases like schizophrenia, certain addictions, and behavioural patterns, such as those that regulate appetite or mood”, he adds. The signalling pathways involved in each process must now be studied in order to develop the treatments, the molecules, for addressing these pathologies.

Reference article

Stepniewski TMMancini A, Agren R, Torrens-Fontanals M, M Semache, Bouvier M, Sahlholm K, Breton BSelent J. Mechanistic insights into dopaminergic and serotonergic neurotransmission-concerted interactions with helices 5 and 6 drive the functional outcome. Chem Sci, 2021 DOI: 10.1039/D1SC00749A.

Provided by IMIM

Chronic Pain Might Impact How The Brain Processes Emotions (Neuroscience)

Neurotransmitters help regulate our emotions—but scientists have noticed a disruption to their levels in people with chronic pain.

More than 3 million Australians experience chronic pain, an ongoing and often debilitating condition that can last from months to years. This persistent pain can impact many parts of a person’s life, with almost half of people with chronic pain also experiencing major anxiety and depression disorders.

Now, a new study led by UNSW Sydney and NeuRA shows that people with chronic pain have an imbalance of neurotransmitters in the part of the brain responsible for regulating emotions.

This imbalance could be making it harder for them to keep negative emotions in check—and the researchers think persistent pain might be triggering the chemical disruption.

The findings are published today in the European Journal of Pain.

“Chronic pain is more than an awful sensation,” says senior author of the study Associate Professor Sylvia Gustin, a neuroscientist and psychologist at UNSW and NeuRA. “It can affect our feelings, beliefs and the way we are.

“We have discovered, for the first time, that ongoing pain is associated with a decrease in GABA, an inhibitive neurotransmitter in the medial prefrontal cortex. In other words, there’s an actual pathological change going on.”

Neurotransmitters help communicate and balance messages between cells. While some amplify signals (called excitatory neurotransmitters), others weaken them (inhibitive neurotransmitters).

GABA, or γ-aminobutyric acid, is the main inhibitory neurotransmitter in the central nervous system. Its role in the medial prefrontal cortex—the part of the brain where emotional regulation happens—is to help dial down our emotions.

The research team used advanced neurological imaging to scan GABA content in the medial prefrontal cortex of 48 study participants, half of which experienced some form of chronic pain. A/Prof. Gustin says this relatively small sample size is typical for neurological imaging studies, which are costly to run.

The results show that participants with chronic pain had significantly lower levels of GABA than the control group—a pattern that was consistent regardless of their type of chronic pain.

“A decrease in GABA means that the brain cells can no longer communicate to each other properly,” says A/Prof. Gustin.

“When there’s a decrease in this neurotransmitter, our actions, emotions and thoughts get amplified.”

While the link between chronic pain and decreased levels of GABA has previously been found in animal studies, this is the first time it’s been translated to human studies.

A/Prof. Gustin says she hopes the findings are encouraging for people with chronic pain who may be experiencing mental health issues.

“It’s important to remember it’s not you—there’s actually something physically happening to your brain,” she says.

“We don’t know why it happens yet, but we are working on finding solutions on how to change it.”

A chain reaction

GABA is one of many neurotransmitters in the medial prefrontal cortex—and it’s not the only one behaving differently in people with pain.

In a previous study, A/Prof. Gustin and her team found that levels of glutamate, the main excitatory neurotransmitter in the central nervous system, are also lower than average in people with chronic pain. These low glutamate levels were linked to increased feelings of fear, worry and negative thinking.

“Together, our studies show there’s really a disruption in how the brain cells are talking to each other,” says A/Prof. Gustin, who has been researching chronic pain for over 20 years.

“As a result of this disruption, a person’s ability to feel positive emotions, such as happiness, motivation and confidence may be taken away—and they can’t easily be restored.”

A/Prof. Gustin says chronic pain is likely to be the culprit behind these neurological changes. However, this theory could only be tested by scanning participants’ brains both before and after they develop chronic pain—and as brain imaging is expensive to conduct, it’s unlikely such a large-scale project would be possible without major funding.

“Everything starts with stress,” she says. “When someone is in pain, it increases stress hormones like cortisol, which can trigger massive increases in glutamate. This happens during the initial, acute stage of pain.

“Too much glutamate can be toxic to brain cells and brain function. We think this disruption to normal brain function may cause the GABA and glutamate levels to change—and impair a person’s ability to regulate their emotions.”

A new form of treatment

Medication is often used to help treat chronic pain, but there are currently no drugs that directly target the GABA and glutamate content in the medial prefrontal cortex. Instead, medication affects the entire central nervous system, and may come with side effects.

A/Prof. Gustin and her team have recently developed an online emotional recovery program, specifically targeted at people with chronic pain, as a non-pharmaceutical option for treating the neurotransmitter disruption.

The findings will be presented in a paper later this year, but the initial results are encouraging.

“The online therapy program teaches people skills to help self-regulate their negative emotions,” says A/Prof. Gustin, who welcomes people interested in learning more about the program to contact the team.

“The brain can’t dampen down these feelings on its own, but it is plastic—and we can learn to change it.”

Featured image: Regulating emotions might be harder for people with chronic pain, the study finds. Credit: Shutterstock

Reference: David Kang et al, Disruption to normal excitatory and inhibitory function within the medial prefrontal cortex in people with chronic pain, European Journal of Pain (2021). DOI: 10.1002/ejp.1838

Provided by University of New South Wales

Fruit Fly Study Reveals Function Of Taste Neurons (Neuroscience)

UC Riverside study shows food choice decisions require taste input

What can the fruit fly teach us about taste and how chemicals cause our taste buds to recognize sweet, sour, bitter, umami, and salty tastes? Quite a lot, according to University of California, Riverside, researchers who have published a study exploring the insect’s sense of taste.

“Insect feeding behavior directly impacts humans in many ways, from disease-carrying mosquitos that seek human blood to pests whose appetite can wreak havoc on the agricultural sector,” said Anupama Dahanukar, an associate professor of molecular, cell and systems biology, who led the study appearing in the Journal of Neuroscience. “How insect taste neurons are organized and how they function is critical for a deeper understanding of their feeding behavior.”

The fruit fly has multiple taste organs throughout its body to detect chemicals, called tastants, that signal whether a food is palatable or harmful. It is still unclear, however, how individual neurons in each taste organ act to control feeding. To explore this question, Dahanukar’s team used the fly pharynx as a model to study whether taste information regulates sugar and amino acid consumption at the cellular level.

Anupama Dahanukar and David Chen and Ryan Matthew Joseph
Anupama Dahanukar (left), Yu-Chieh David Chen (center) and Ryan Matthew Joseph. © University of California Riverside

Dahanukar explained animals rely heavily on the sense of taste to make feeding decisions, such as consuming nutritive foods while avoiding toxic ones. 

“In mammals, taste information is encoded by specialized cells present in taste buds of the tongue,” she said. “Taste receptors expressed in these cells can detect different chemicals. Molecular and functional differences in receptors expressed in different cells allow recognition of different tastes, such as salty, sour, sweet, bitter, or umami.”

Several new studies in flies indicate individual taste neurons can detect compounds belonging to more than one taste category, raising some questions about the distinct behavioral roles of individual taste neurons. If many classes of taste neurons are activated by sugar, for example, how does activation of just one class of taste neurons affect behavior?

Dahanukar’s team answered this question by genetically engineering a fly in which only a single defined class of pharyngeal neurons is active. The team then tested this fly in different feeding experiments to understand what the fly can or cannot do compared to animals that have all their taste neurons intact.

“We found single-taste neurons are capable of responding and activating behavioral responses to more than one tastant category — sweet and amino acids in our study,” said Yu-Chieh David Chen, the first author of the research paper. “We also found that a single tastant category — amino acids in our study — can activate multiple classes of taste neurons.” 

The team also tested flies that had no functional taste neurons. Such flies were incapable of making any proper feeding decisions, no matter the food choices — whether these were two attractive stimuli, one attractive and one aversive, or one nutritive and the other nonnutritive.

The researchers found food choice decisions cannot be made in the absence of taste input; the latter is critical for ensuring appropriate food choice and feeding behavior. Further, flies that had pharyngeal sweet taste neurons as the only source of taste input were consistently able to select more palatable food. 

“Altogether, our results argue for the existence of a combinatorial coding system, wherein multiple neurons coordinate the response to any given tastant,” Dahanukar said.

The study is the first to directly test the impact of loss of all taste neurons on behavioral responses to tastants of different categories. It is also the first to test whether a single class of taste neurons is sufficient for food choice and feeding behavior.

“Along with several other recent studies in the field, our work also invites revisiting some established ideas about how insect taste is organized,” Dahanukar said. “Rather than encoding tastes as in mammals, flies appear to encode some combination of valence — attractive versus aversive — and tastant identity.”

Her team anticipates that knowing how taste neurons work in flies will facilitate insect studies of greater health or agricultural importance. 

“We are building tools for asking the same sorts of questions in mosquitoes,” Dahanukar said. “Such studies could offer potential targets for manipulating feeding behaviors of pests or disease vectors in surveillance or control strategies.”

She acknowledged that her lab has only evaluated a single taste neuron within the system it set up, with many more remaining to be studied. 

Vaibhav Menon
Vaibhav Menon. © University of California Riverside

“We are interested in understanding what these neurons sense and how they act, individually and as part of a group, to control parameters that lead to either promotion or cessation of food intake,” said Vaibhav Menon, a graduate student in Dahanukar’s lab and a co-author on the study. 

The team plans to apply some of the same strategies to investigate how feeding behavior is controlled in mosquitoes.

Dahanukar, Chen, and Menon were joined in the study by Ryan Matthew Joseph. Chen is now at New York University; Joseph is at Riverside City College.

The study was supported by the Whitehall Foundation, National Institutes of Health, National Institute of Food and Agriculture of the U.S. Department of Agriculture, and UCR Agricultural Experimental Station. Chen was a Howard Hughes Medical Institute International Student Research Fellow at UCR.

The research paper is titled “Control of sugar and amino acid feeding via pharyngeal taste neurons.”

Provided by UCR

How the Brain Paints the Beauty of a Landscape? (Neuroscience)

How does a view of nature gain its gloss of beauty? We know that the sight of beautiful landscapes engages the brain’s reward systems. But how does the brain transform visual signals into aesthetic ones? Why do we perceive a mountain vista or passing clouds as beautiful? A research team from the Max Planck Institute for Empirical Aesthetics has taken up this question and investigated how our brains proceed from merely seeing a landscape to feeling its aesthetic impact.

In their study, the research team presented artistic landscape videos to 24 participants. Using functional magnetic resonance imaging (fMRI), they measured the participants’ brain activity as they viewed and rated the videos. Their findings have just been published in the open-access journal Frontiers in Human Neuroscience. First author A. Ilkay Isik encapsulates:

“We would have expected the aesthetic signals to be limited to the brain’s reward systems, but surprisingly, we found them already present in visual areas of the brain while the participants were watching the videos. The activations occurred right next to brain regions deployed in recognizing physical features in movies, such as the layout of a scene or the presence of motion.”

Senior author Edward Vessel suggests that these signals may reflect an early, elemental form of beauty perception:

“When we see something beyond our expectations, local patches of brain tissue generate small ‘atoms’ of positive affect. The combination of many such surprise signals across the visual system adds up to make for an aesthetically appealing experience.”

With this new knowledge, the study not only contributes to our understanding of beauty, but may also help clarify how interactions with the natural environment can affect our sense of well-being. The results might have potential applications in a variety of fields where the link between perception and emotion is important, such as clinical health care and artificial intelligence.

Featured image: A research team from the Max Planck Institute for Empirical Aesthetics investigated how our brains proceed from merely seeing a landscape to feeling its aesthetic impact. (Illustration: MPI for Empirical Aesthetics)

Original Publication:
Isik, A.I. and Vessel, E.A. (2021). From Visual Perception to Aesthetic Appeal: Brain Responses to Aesthetically Appealing Natural Landscape Movies. Front. Hum. Neurosci. 15:676032. doi:10.3389/fnhum.2021.676032

Provided by Max Planck Institute for Empirical Aesthetics

Researchers Discovered Brain-repair Process That Could Lead to New Epilepsy Treatments (Neuroscience)

School of Medicine researchers have discovered a previously unknown repair process that takes place in the brain that they hope could be harnessed and enhanced to treat seizure-related brain injuries.

Common seizure-preventing drugs do not work for approximately a third of epilepsy patients, so new and better treatments for such brain injuries are much needed. UVA’s discovery identifies a potential avenue, one inspired by the brain’s natural immune response.

Using high-powered imaging, the researchers were able to see, for the first time, that immune cells called microglia were not just removing damaged material after experimental seizures but actually appeared to be healing damaged neurons.

“There has been mounting generic support for the idea that microglia could be used to ameliorate seizures, but direct, visualized evidence for how they could do this has been lacking,” said researcher Ukpong B. Eyo, PhD, of UVA’s Department of Neuroscience, the UVA Brain Institute and UVA’s Center for Brain Immunology and Glia (BIG). “Our results indicate that microglia may not be simply clearing debris but providing structural support for neuronal integrity that may have implications even beyond the scope of seizures and epilepsy.”


The new findings come from a collaboration of scientists at UVA, Mayo Clinic and Rutgers University. They used an advanced imaging technique called two-photon microscopy to examine what happened in the brains of lab mice after severe seizures. What they saw was strange and unexpected.

Rather than simply cleaning up debris, the microglia began forming pouches. These pouches didn’t swallow up damaged material, as many immune cells do. Instead, they began tending to swollen dendrites – the branches of nerve cells that transmit nerve impulses. They weren’t removing, the scientists realized; they appeared to be healing.

These odd little pouches – the scientists named them “microglial process pouches” – stuck around for hours. They often shrank, but they were clearly doing something beneficial because the dendrites they targeted ended up looking better and healthier than those they didn’t.

“We did not find microglia to be ‘eating’ the neuronal elements in this context,” Eyo said. “Rather, we saw a strong correlation between these interactions and a structural resolution of injured neurons suggestive of a ‘healing’ process.”

The new insights into the brain’s immune response points scientists in promising new directions. “Although these findings are exciting, there is yet a lot to follow-up on them. For example, the precise mechanisms that regulate the interactions remain to be identified. Moreover, at present, the ‘healing’ feature is suggested from correlational results and more definitive studies are required to certify the nature of the ‘healing,’” Eyo said. “If these questions can be answered, they will provide a rationale for developing approaches to enhance this process … in seizure contexts.”

Eyo has already received two grants totaling almost $5 million from the National Institutes of Health to continue his study of microglia. The funding will allow him to study how the immune cells help regulate vascular function, which could be important in diseases such as Alzheimer’s, and their role in brain-hyperactivity disorders such as febrile seizures that can trigger epilepsy.

“With this new funding, we are eager to clarify roles for microglia in seizure disorders and vascular function,” he said. “UVA’s continued investment is neuroscience research provides a suitable home for our lab’s research.”


The researchers have published their findings in the scientific journal Cell Reports. The research team consisted of Eyo, Koichiro Haruwaka, Mingshu Mo, Antony Brayan Campos-Salazar, Lingxiao Wang, Xenophon S. Speros IV, Sruchika Sabu, Pingyi Xu and Long-Jun Wu. DOI: https://doi.org/10.1016/j.celrep.2021.109080

The research was supported by National Institutes of Health grants R01NS088627, R01NS112144 and K22N84392. Eyo’s new NIH grants are R01NS119243 and R01NS122782.

Featured image: Ukpong B. Eyo, PhD © Dan Addison | UVA Communications

Provided by UVA Health

Parkinson’s Disease: How Lysosomes Become A Hub For The Propagation Of The Pathology (Neuroscience)

Over the last few decades, neurodegenerative diseases became one of the top 10 global causes of death. Researchers worldwide are making a strong effort to understand neurodegenerative diseases pathogenesis, which is essential to develop efficient treatments against these incurable diseases. However, our knowledge about the basic molecular mechanisms underlying the pathogenesis of neurodegenerative diseases is still lacking. A team of researchers found out the implication of lysosomes in the spread of Parkinson’s disease.

The accumulation of misfolded protein aggregates in affected brain regions is a common hallmark shared by several neurodegenerative diseases (NDs). Mounting evidence in cellular and in animal models highlights the capability of different misfolded proteins to be transmitted and to induce the aggregation of their endogenous counterparts, this process is called “seeding”. In Parkinson’s disease, the second most common ND, misfolded α-synuclein (α-syn) proteins accumulate in fibrillar aggregates within neurons. Those accumulations are named Lewy bodies.

α-syn fibrils spreads through TNTs inside lysosomes

In 2016, a team of researchers from the Institut Pasteur (Paris) and the French National Centre for Scientific Research (in French: CNRS, Centre national de la recherche scientifique) demonstrated that α- syn fibrils spread from donor to acceptor cells through tunneling nanotubes (TNTs). They also found out that these fibrils are transferred through TNTs inside lysosomes. “TNTs are actin-based membrane channels allowing the transfer of several cellular components including organelles between distant cells. Lysosomes are organelles normally deputed to the degradation and recycling of toxic/damaged cell material” describes Chiara Zurzolo, head of the Membrane Traffic and Pathogenesis Unit at the Institut Pasteur.

α-syn fibrils can modify lysosome shape and permeability to allow seeding and diffusion

Following this original discovery, researchers, now shed some light on how lysosomes participate in the spreading of α-syn aggregates through TNTs. “By using super-resolution and electron microscopy, we found that α-syn fibrils affect the morphology of lysosomes and impair their function in neuronal cells. We demonstrated for the first time that α-syn fibrils induce the peripheral redistribution of the lysosomes thus increasing the efficiency of α-syn fibrils’ transfer to neighbouring cells,” continues Chiara Zurzolo. They also showed that α-syn fibrils can permeabilize the lysosomal membrane, impairing the degradative function of lysosomes and allowing the seeding of soluble α-syn, which occurs mainly in those lysosomes. Thus, by impairing lysosomal function α-syn fibrils block their own degradation in lysosomes, that instead become a hub for the propagation of the pathology.


This discovery contributes to the elucidation of the mechanism by which α-syn fibrils spread through TNTs, while also revealing the crucial role of lysosomes, working as a Trojan horse for both seeding and propagation of disease pathology. This information can be exploited to establish novel therapies to target these incurable diseases.


α-Synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubesPlos Biology, July 20 2021

Provided by Institut Pasteur

Brain ‘Noise’ Keeps Nerve Connections Young (Neuroscience)

Neurons communicate through rapid electrical signals that regulate the release of neurotransmitters, the brain’s chemical messengers. Once transmitted across a neuron, electrical signals cause the juncture with another neuron, known as a synapse, to release droplets filled with neurotransmitters that pass the information on to the next neuron. This type of neuron-to-neuron communication is known as evoked neurotransmission.

However, some neurotransmitter-packed droplets are released at the synapse even in the absence of electrical impulses. These miniature release events — or minis — have long been regarded as ‘background noise’, says Brian McCabe, Director of the Laboratory of Neural Genetics and Disease and a Professor in the EPFL Brain Mind Institute.

But several studies have suggested that minis do have a function — and an important one. In 2014, for example, McCabe and his team showed that minis are important for the development of synapses. If neurons in the brain were a network of computers, evoked releases would be packets of data through which the machines exchange information, whereas minis would be pings — brief electronic signals that determine if there is a connection between two computers, McCabe says. “Minis are the pings that neurons use to say ‘I am connected.'”

Adult Drosophila motor terminals (green) and muscles (red) progressively degenerate with age © Laboratory of Neural Genetics and Disease / EPFL

To assess whether minis could play a role in the mature nervous system, Soumya Banerjee, a postdoc in McCabe’s group, and his colleagues set out to study a set of neurons that control movement in fruit flies. As the insects aged, their synapses started to break up into smaller fragments, the researchers found. (A similar process occurs in aging mammals, including people.) As nerve junctions broke down, both evoked and miniature neurotransmission were dampened, and the flies showed motor problems such as a reduced ability to climb the walls of a plastic vial.

Next, the team assessed the effects of stimulating or inhibiting evoked and miniature neurotransmission. When both types of neurotransmission were blocked, synapses aged prematurely, suggesting that during aging or in neurological diseases associated with old age, changes in neurotransmission happen before synapses start to crumble. This finding, McCabe says, upends a longstanding idea in neuroscience. “The idea has long been that the structure of the synapse breaks down, and that causes a functional change in the synapse, but we found it is the other way around,” he says.

Adult Drosophila neuromuscular synaptic terminals. Motor neurons (blue), synaptic boutons (red) and neurotransmitter release sites (green). © Laboratory of Neural Genetics and Disease / EPFL

Stimulating evoked neurotransmission alone had no effect on aging synapses, the researchers found. However, increasing the frequency of minis kept synapses intact and preserved the motor ability of middle-aged flies at levels comparable to those of young flies. “Motor ability declines in all aging animals, including humans, so it was a delightful surprise to see that we could change that,” McCabe says.

The findings, published in Nature Communications, could have important implications for human health: minis have been found at every type of synapse studied so far, and defects in miniature neurotransmission have been linked to range of neurodevelopmental disorders in children. Figuring out how a reduction in miniature neurotransmission changes the structure of synapses, and how that in turn affects behavior, could help to better understand neurodegenerative disorders and other brain conditions.

Featured image: Brian McCabe, Director of the Laboratory of Neural Genetics and Disease and a Professor in the EPFL Brain Mind Institute. © Alain Herzog / EPFL

Reference: Banerjee, S., Vernon, S., Jiao, W. et al. Miniature neurotransmission is required to maintain Drosophila synaptic structures during ageing. Nat Commun 12, 4399 (2021). https://doi.org/10.1038/s41467-021-24490-1

Provided by EPFL