Cell Biology

White blood cells play unexpected role in clearing out dead liver cells – EurekAlert

A type of white blood cell usually associated with immune responses to foreign particles may have another role in clearing out liver cells that have undergone apoptosis where cells are programmed to die in a controlled manner.

The study, published today as a Reviewed Preprint in eLife, provides what the editors describe as solid evidence that neutrophils destroy liver cells going through apoptosis by burrowing into them a process the authors have called perforocytosis. The findings also suggest that a lack of neutrophils may be a cause of human autoimmune liver disease (AIL), with potential implications for new therapeutic strategies against the disease.

Billions of apoptotic cells are removed daily in adults by a group of immune cells called phagocytes. Neutrophils represent around 5070% of the total white blood cell population in humans and are a type of phagocyte. However, unlike other phagocytes, they were widely assumed to be excluded from apoptotic cells, as they promote inflammation which could damage nearby healthy cells and tissues. The current findings now challenge that assumption.

Although apoptotic cells are well characterised, they are not often found within human samples, possibly because they are removed so efficiently by phagocytes, says co-lead author Luyang Cao, Associate Investigator in the Department of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, China. This means that the specific phagocytes responsible for the removal of apoptotic cells remain unknown, and we do not know if they are specific to different tissues in the body.

To identify the phagocytes responsible for removing apoptotic cells in the liver, the team obtained cells from the liver tissue of patients with tumours caused by hepatocellular carcinoma or hepatic hemangioma. They used two different staining techniques to confirm which cells in the sample were apoptotic.

In a total of 281 apoptotic liver cells from the livers of 32 patients, the team noticed that each cell was engorged by the presence of up to 22 neutrophils. It has previously been suggested that a type of phagocyte called Kupffer cells were responsible for the clearance of apoptotic liver cells, but when the researchers searched for Kupffer cells in the samples, they found that very few were present. They therefore hypothesised that neutrophils were the primary phagocyte for the removal of dead liver cells through the process they called perforocytosis. This contrasts to the usual process of engulfing apoptotic cells that most other phagocytes use.

To confirm the mechanism by which neutrophils remove apoptotic liver cells, the team sought to visualise the process in mouse livers using intravital microscopy a live imaging technique that allows biological processes to be viewed in real time within living organisms. They labelled liver cells with a protein called Annexin V and neutrophils with an anti-Ly6G antibody. Consistent with their findings in human samples, the team observed that neutrophils burrowed into and cleared dead liver cells in the mice. The process was fast and rigorous, with the dead cells completely digested in four to seven minutes.

Our discovery of neutrophils burrowing into and clearing out apoptotic liver cells helps to solve some of the mysteries surrounding the apoptotic clearance process, says co-corresponding author Hexige Saiyin, Assistant Professor in the State Key Laboratory of Genetic Engineering, School of Life Sciences,Fudan University, China.

Next, the team sought to investigate whether reducing the neutrophil population in mice impacts the clearance of apoptotic liver cells. In a sample of cells from the livers of neutrophil-depleted mice, the percentage of apoptotic cells was significantly higher than in normal mice 0.92% and 0.2%, respectively suggesting that neutrophil depletion impairs the clearance of apoptotic cells. They also noticed the presence of other phagocytes in the neutrophil-depleted mice, implying a compensatory role of other phagocytes in the absence of neutrophils.

The defective clearance of apoptotic cells is often linked with autoimmune diseases, such as AIL. In the neutrophil-depleted mice, the team noticed an increase in autoantibodies immune cells that mistakenly attack the bodys own healthy cells instead of foreign bodies such as viruses or bacteria. This increase was unaffected by antibiotic treatments and present only in neutrophil-depleted mice, not in mice with other phagocyte depletions. This implies that neutrophil depletion is associated with impaired apoptotic liver cell clearance and, subsequently, the generation of autoantibodies that may lead to AIL disease. The team consolidated this finding by analysing biopsy samples from human patients with AIL disease. Once again they found that, in each patient, the neutrophil-mediated clearance of apoptotic cells was impaired.

The authors say that more research is needed to better understand the process and significance of perforocytosis, as well as whether perforocytosis occurs in other organs besides livers. The next important step is how to apply this newly identified apoptotic clearance mechanism to the clinical treatment of AIL.

Since the failure to clear dead cells is linked to inflammatory and autoimmune diseases, further insights into the critical role that neutrophils play in apoptotic clearance may have important implications for the treatment of these diseases. We recently have screened and identified several compounds which markedly enhanced neutrophil perforocytosis and demonstrated great therapeutic values to cure AIL in mouse models. concludes senior author Jingsong Xu, former Principal Investigator at the Department of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University (current address: Department of Pharmacology, Center for Lung and Vascular Biology, University of Illinois, Chicago).

##

Reference

The Reviewed Preprint, An unexpected role of neutrophils in clearing apoptotic hepatocytes in vivo, is available to view at https://doi.org/10.7554/eLife.86591.1. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

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About eLife

eLife transforms research communication to create a future where a diverse, global community of scientists and researchers produces open and trusted results for the benefit of all. Independent, not-for-profit and supported by funders, we improve the way science is practised and shared. In support of our goal, weve launched a new publishing model that ends the accept/reject decision after peer review. Instead, papers invited for review will be published as a Reviewed Preprint that contains public peer reviews and an eLife assessment. We also continue to publish research that was accepted after peer review as part of our traditional process. eLife receives financial support and strategic guidance from the Howard Hughes Medical Institute, Knut and Alice Wallenberg Foundation, the Max Planck Society and Wellcome. Learn more at https://elifesciences.org/about.

To read the latest Medicine research published in eLife, visit https://elifesciences.org/subjects/medicine.

An Unexpected Role of Neutrophils in Clearing Apoptotic Hepatocytes In Vivo

4-Apr-2023

The authors declare that no competing interests exist

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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White blood cells play unexpected role in clearing out dead liver cells - EurekAlert

Cell Biology

Woolly mammoths evolved smaller ears and woolier coats over the 700,000 years that they roamed the Siberian steppes – Newswise

Newswise A team of researchers compared the genomes of woolly mammoths with modern day elephants to find out what made woolly mammoths unique, both as individuals and as a species. The investigators report April 7 in the journalCurrent Biologythat many of the woolly mammoths trademark featuresincluding their woolly coats and large fat depositswere already genetically encoded in the earliest woolly mammoths, but these and other traits became more defined over the species 700,000+ year existence. They also identified a gene with several mutations that may have been responsible for the woolly mammoths miniscule ears.

We wanted to know what makes a mammoth a woolly mammoth, says paleogeneticist and first author David Dez-del-Molino (@indianadiez) of the Centre for Palaeogenetics in Stockholm. Woolly mammoths have some very characteristic morphological features, like their thick fur and small ears, that you obviously expect based on what frozen specimens look like, but there are also many other adaptations like fat metabolism and cold perception that are not so evident because theyre at the molecular level.

To identify genes that were highly evolved in woolly mammoths meaning they had accrued a large number of mutationsthe team compared the genomes of 23 Siberian woolly mammoth with 28 modern-day Asian and African elephant genomes. Twenty-two of these woolly mammoths were relatively modern, having lived within the past 100,000 years, and sixteen of the genomes had not been previously sequenced. The twenty-third woolly mammoth genome belonged to one of the oldest known woolly mammoths, Chukochya, who lived approximately 700,000 years ago.

Having the Chukochya genome allowed us to identify a number of genes that evolved during the lifespan of the woolly mammoth as a species, says senior author Love Daln (@love_dalen), professor of evolutionary genomics at the Centre for Palaeogenetics in Stockholm. This allows us to study evolution in real time, and we can say these specific mutations are unique to woolly mammoths, and they didn't exist in its ancestors.

Not surprisingly, many genes that were adaptive for woolly mammoths are related to living in cold environments. Some of these genes are shared by unrelated modern-day Arctic mammals. We found some highly evolved genes related to fat metabolism and storage that are also found in other Arctic species like reindeer and polar bears, which means theres probably convergent evolution for these genes in cold-adapted mammals, says Dez-del-Molino.

While previous studies have looked at the genomes of one or two woolly mammoths, this is the first comparison of a large number of mammoth genomes. This large sample size enabled the team to identify genes that were common among all woolly mammoths, and therefore likely adaptive, as opposed to genetic mutations that might only have been present in a single individual.

We found that some of the genes that were previously thought to be special for woolly mammoths are actually variable between mammoths, which means they probably weren't as important, says Dez-del-Molino.

Overall, the 700,000-year-old Chukochya genome shared approximately 91.7% of the mutations that caused protein-coding changes in the more modern woolly mammoths. This means that many of the woolly mammoths defining traitsincluding thick fur, fat metabolism, and cold-perception abilitieswere probably already present when the woolly mammoth first diverged from its ancestor, the steppe mammoth.

However, these traits developed further in Chukochyas descendants. The very earliest woolly mammoths weren't fully evolved, says Daln They possibly had larger ears, and their wool was differentperhaps less insulating and fluffy compared to later woolly mammoths.

More modern woolly mammoths also had several immune mutations in T cell antigens that were not seen in their ancestor. The authors speculate that these mutations may have conferred enhanced cell-mediated immunity in response to emerging viral pathogens.

Working with ancient mammoth DNA comes with a slew of hurdles. Every step of the way, things are a bit more difficult, from fieldwork, to lab work, to bioinformatics, says Dez-del-Molino.

Apart from the field work, where we have to battle both polar bears and mosquitos, another aspect that makes this much more difficult is that you have to work in an ancient DNA laboratory, and that means that you have to dress up in this full-body suit with a hood and face mask and visor and double gloves, so doing the lab work is rather uncomfortable to put it mildly, says Daln. I would like to highlight Marianne Dehasque, the second author of this paper, who did the herculean effort of performing lab work on most of these samples.

All the mammoths whose genomes were included in this study were collected in Siberia, but the researchers hope to branch out and compare North American woolly mammoths in the future. We showed a couple of years ago that there was gene flow between woolly mammoths and the ancestors of Colombian mammoths, so thats something that we will need to account for because North American woolly mammoths might have been carrying non-woolly mammoth genes as well, says Daln.

###

This research was supported by the Swedish Research Council, FORMAS, the Carl Tryggers Foundation, the SciLifeLab, the Wallenberg Data Driven Life Science Program, the Wallenberg Academy, and the Russian Science Foundation.

Current Biology, Dez-del-Molino et al. Genomics of adaptive evolution in the woolly mammothhttps://www.cell.com/current-biology/fulltext/S0960-9822(23)00404-9

Current Biology(@CurrentBiology), published by Cell Press, is a bimonthly journal that features papers across all areas of biology.Current Biologystrives to foster communication across fields of biology, both by publishing important findings of general interest and through highly accessible front matter for non-specialists. Visit:http://www.cell.com/current-biology.

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Neuroscience

Announcing the Hackensack Meridian Health Neuroscience Institute … – Hackensack Meridian Health

Hackensack Meridian Healths three nationally-recognized neuroscience institutes at Hackensack University Medical Center, Jersey Shore University Medical Center and JFK University Medical Center are now united as Hackensack Meridian Neuroscience Institute the largest, most comprehensive Neuroscience Institute in the state. By coming together as one institute with a shared vision and mission, the three locations have strengthened their ability to provide integrated access to care and research for patients throughout New Jersey.

Under the Hackensack Meridian Neuroscience Institute umbrella, neurology and neurosurgery team members are able to leverage the network resources to provide their patients with enhanced access to evidence-based care protocols, clinical trials, technology, and subspecialty expertise closer to home, and without the need to refer patients outside HMH.

One in three people will develop a neurological disorder at some point. Neurological disorders are the leading cause of disability and among the leading causes of death in the United States. That is why where and who a patient seeks treatment for conditions like brain and spine tumors, Parkinson's disease and other movement disorders, stroke, epilepsy, Alzheimers disease, and dementia and neuromuscular diseases like multiple sclerosis, is important.

The Hackensack Meridian Neuroscience Institute offers the highest standard of care for patients with neurological illnesses, allowing us to bring together neurologists, neurosurgeons and other neurology specialists including neuropsychologists, case managers, neurointensivists, researchers and neuro-oncologists so that every facet of a neurological illness is attended to, said Timothy Hogan, FACHE, executive vice president of Hackensack Meridian Health Care Transformation Services. The Institute allows for even greater connectivity and collaboration, to allow patients access to the highest quality care in all the regions we serve throughout New Jersey.

Hackensack Meridian Health has the largest neurology and neurosurgery program in New Jersey and is home to the states only nationally ranked neurology and neurosurgery program at Hackensack University Medical Center. The Neuroscience Institutes accolades include the following:

Patients will also have access to nationally ranked neurological rehabilitation services at the JFK Johnson Rehabilitation Institute, ranked by US News & World Report as one of the top rehabilitation hospitals in the country.

The Hackensack Meridian Neuroscience Institute allows patients access to state-of-the-art care and advanced therapies through new research and clinical trials, including trials in neurological conditions like amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Alzheimers disease, Charcot-Marie-Tooth disease (CMT), spinal cord injury, brain tumors and migraines.

Collaboration throughout Hackensack Meridian Healths vast healthcare network allows other underlying medical causes for neurological disorders to be addressed. For example, Hackensack University Medical Center has established a Heart and Brain Clinic to evaluate and treat people with patent foramen ovale (PFO) a small hole in the heart who have had a stroke not due to other causes and who are at risk of a second stroke. The clinic is a collaboration between the medical centers renowned cardiology and neurology experts in one multidisciplinary program and is the first-of-its-kind in New Jersey. At the Neuroscience Institutes Center for Memory Loss and Brain Health, patients have access to cognitive neurologists, geriatricians, health & neuro-psychologists and social workers for comprehensive care to all parts of memory loss diseases.

Hackensack Meridian Neuroscience Institute Offers Advanced Technology

The Neuroscience Institute offers premiere technology for treatment of neurological disease and disorders that cannot be found at most other institutions. The Neuroscience Institute is now equipped with Quicktome brain mapping technology, an innovation in imaging to map brain networks and electrical connections to preserve them during surgery, allowing surgeons to plot out a surgery that would limit the amount of brain tissue impacted. The Hackensack Meridian Neuroscience Institute sites are the first locations in New Jersey and only a few in the Northeast with this technology.

The Neuroscience Institute at Hackensack University Medical Center is home to New Jerseys first intraoperative MRI system, used during neurosurgical and neuro-interventional procedures to help neurosurgeons accurately remove tumors and treat conditions such as Parkinsons disease, epilepsy and more. Similar technology, including Clear Point brings MRI technology into the operation room, allowing patients to undergo deep brain stimulation (DBS) while asleep rather than awake.

The Hackensack Meridian Neuroscience Institute at Hackensack University Medical Center and later this year, Jersey Shore University Medical Center are the only locations in New Jersey to offer High Intensity Focused Ultrasound (HiFU). This unique non-invasive procedure effectively treats Parkinsons tremors and essential tremors in cases where managing with medication hasnt been effective, allowing patients to return to their normal activities without debilitating tremors.

For the treatment of brain cancer and other conditions of the head and neck, the Neuroscience Institute at Jersey Shore University Medical Center will offer Zap-X beginning this summer, a non-invasive precision treatment that delivers high-dose radiation to brain tumors, facial pain and arteriovenous malformations or twisted blood vessels that can cause clots leading to stroke, without destroying healthy brain cells. The Neuroscience Institute will be the sixth in the nation to have Zap-X, the only one in the Northeast, and globally the first to pair it with Synaptive MRI, shortening the time from diagnosis to treatment. The Neuroscience Institute also skillfully uses gamma knife and fluorescence-targeted radiation in the treatment of brain tumors, tremors and other neurological issues.

If brain or spine surgery is required, the Neuroscience Institute at JFK University Medical Center is one of a handful of hospitals nationally and the only one in New Jersey offering 3D imaging technology and intraoperative augmented reality imaging during surgery known as Surgical Theater. Neurosurgeons slip on a virtual reality headset and see exceptionally detailed images to determine the best strategy to target pathologies while preserving normal tissue. Doctors also use this technology to practice a surgery before they perform it and to demonstrate to patients what needs to be done.

Other technology available at the Hackensack Meridian Neuroscience Institute include Laser Interstitial Thermal Therapy (LiTT Technology), a minimally invasive surgical option for people with drug-resistant epilepsy and select brain tumors. DaTSCAN Camera, one of the most advanced diagnostic imaging technologies available, visualizes dopamine transporter levels in the brain. This is an effective tool in diagnosing Parkinsons disease and other movement disorders.

Neuroscience Institute surgeons are skilled at using DBS to surgically implant a pacemaker-type device into the brain to control tremors. For sleep disorders, the Hackensack Meridian Neuroscience Institute offers two surgical options for obstructive sleep apnea that cannot be controlled with a CPAP machine.

Hackensack Meridian Neuroscience Institute Has World-Class Physicians

The Neuroscience Institutes advanced technology is even more powerful in the hands of its world-class physicians. From neurology, neuro-surgery, neuro-oncology, movement disorders, stroke, memory disorders, sleep, and headaches, the Hackensack Meridian Neuroscience Institute offers expert physicians in all areas. The Institutes doctors are leaders and innovators in neurological treatments and surgeries. Bringing them all together in one institute allows more collaboration to combat a patients illness.

No matter the neurological issue, the Hackensack Meridian Neuroscience Institute has a specialist ready to treat it with knowledge, compassion, and state-of-the-art tools in the hands of our renowned neurologists, neurosurgeons, and neuro-oncologists, said Maria Coello, vice president of Care Transformation Services including Neurosciences, Hackensack Meridian Health.

Hackensack Meridian Neuroscience Institute Participates in Groundbreaking Research

The Hackensack Meridian Neuroscience Institute continues to innovate new treatments for neurological ailments, as technology and science evolve, participating in clinical trials and groundbreaking research. Neuroscience Institute patients are able to access cutting-edge technology and treatment breakthroughs for their neurological disorders.

Scientists at the Hackensack Meridian Neuroscience Institute are researching and participating in clinical trials on topics including treatments for traumatic brain injury, Alzheimers disease, multiple sclerosis, and stroke.

Teaching Future Physicians at Hackensack Meridian School of Medicine

The physicians at the Hackensack Meridian Neuroscience Institute are also professors at the Hackensack Meridian School of Medicine, the first private medical school opened in New Jersey in more than 50 years, which is training the next generation of neurologists and neurosurgeons on the innovative treatments and advancements being made. The School of Medicines progressive curriculum trains future doctors to not only treat a patients medical condition, but the underlying social determinants of health affecting them. The unique school trains diverse doctors who look like the country and the patients they serve. Nearly half of the class admitted in 2020 is female, and students speak 33 languages. Half of the class identifies as persons of color (other than white), and a quarter are from groups categorized as under-represented in medicine. Studies show patients are more likely to respond to a doctor from their cultural or ethnic background. More than half of the School of Medicine students go on to residencies at Hackensack Meridian hospitals, including within the Neuroscience Institute.

The new Hackensack Meridian Neuroscience Institute advertising campaign launches the week of April 3. Click here to watch our new television commercial.

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Announcing the Hackensack Meridian Health Neuroscience Institute ... - Hackensack Meridian Health

Neuroscience

CZIs Grant for Diversity in Neuroscience is a Positive Development … – Inside Philanthropy

With its February announcement of a two-year, $1 million grant to a new Baltimore initiative focused on racial disparities in the field of neuroscience, the Chan-Zuckerberg Initiative didnt just take another step toward its goal of funding research leading to the cure or treatment of all human disease by the end of this century. The grant is also a step toward ensuring that fewer people will be left out of both the process and the benefits of that research.

CZIs grant will help fund the development of the African Ancestry Neuroscience Research Initiative (AANRI), a partnership between Baltimores Lieber Institute for Brain Development, historically Black Morgan State University, and community leaders helmed by the Rev. Dr. Alvin C. Hathaway, the retired pastor of West Baltimores Union Baptist Church. First announced in 2019, AANRIs aims include alleviating the Black communitys distrust of the medical and research establishment, eventually improving health outcomes by vastly increasing the racial diversity of donated brains available to neuroscientists studying the causes and treatments of everything from psychiatric disorders to Alzheimers Disease, and diversifying the field of neuroscience itself. AANRI has also attracted support from the Abell Foundation, Brown Capital Management, and the state of Maryland.

When it comes to the ways that the countrys health care system has betrayed and failed Black Americans, the infamous Tuskegee syphilis experiments of the 20th century are just one example of medicines many tresspasses. Other examples of medical neglect and outright abuse of Black patients includes forced sterilization, frequent failures to treat their pain or take it seriously, and the disparate toll of the COVID-19 pandemic.

There are also glaring disparities among practitioners. Only 4% of American physicians are Black, and its too early to tell whether the notable increase in Black medical school applicants in 2021 will translate to more representation in the profession. Given that history and todays reality, it shouldnt come as a surprise that underrepresented minority groups, including Black Americans, comprise less than 5% of the research cohorts in neuroscience research studies.

The lack of Black representation in neuroscience research subjects is a real problem in a country where Black Americans are twice as likely to develop Alzheimers, 20% more likely to develop serious mental health problems, and suicide rates for Black children under 13 are twice as high as the rates of children of European ancestry, according to AANRIs website.

Increasing the diversity of donated brains to study isnt just about being representative for the sake of being representative and fair and proportionate, said CZI Science Program Officer Katja Brose, who holds a Ph.D. in biochemistry. Instead, she said, its about bringing a deep and thorough level of science to bear on questions like the contributions of differences in genetics, or how much of an impact differing environments and life experiences, including experiences of racism, have on determining who may develop a brain disorder.

To put it another way, we dont even know what we dont know, said Patricia Flores, a senior communications associate at CZI who works closely with several of the funders scientists. We just know that were missing a large swath of the pot. The majority of the globe is being missed in the science that we understand today.

Is science funding diversifying?

CZIs grant to develop AANRI is only one of several moves in the past few years aiming to promote more diversity in the sciences. In 2021, for example, the MacArthur Foundation committed $2 million to the Native Biodata Consortium, the worlds first Indigenous-led bio-repository, which, like AANRI, is also working to both diversify the field of medical research and help insure that the subjects of that research benefit from its results. Last year, the Howard Hughes Medical Institute launched a $2 billion initiative to diversify academic science more broadly.

CZI is also no stranger to moving money to promote greater diversity in the sciences. A quick look at the funders grants database reveals money being moved to scientific organizations focused on underrepresented groups, efforts like AANRI to diversify sample studies, and, in a 2021 grant to the Americas Health Foundation, efforts to advance a more equitable rare disease advocacy and research ecosystem in the Caribbean and Latin America.

Beyond the anecdotal evidence, its hard to say whether were seeing an overall uptick in funding in this area, but theres definitely a lot of room for more such giving considering the far reach of federal and philanthropic science funding. The National Institutes of Health alone reports that it dedicates most of its $45 billion budget to medical research; last year, one study identified about $30 billion in annual philanthropic funding for scientific work.

One way well truly know whether scientific funding, including money for medical research and to train new scientists and doctors, has truly diversified will be by watching for practical results. Are health disparities improving or disappearing? How common is it for a patient to be seen by a doctor or other health specialist whos Black or another person of color? In the meantime, well do our best to shout out funders efforts to promote diversity in the sciences and call out funders who dont seem to have gotten the memo.

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CZIs Grant for Diversity in Neuroscience is a Positive Development ... - Inside Philanthropy

Neuroscience

SME Topeka welcomes speaker connecting neuroscience to the real world – WIBW

Abortion opponents pushed a bill through the Kansas Legislature early Friday to require providers to tell patients that a medication abortion can be reversed once its started a measure that could face a state court challenge if its supporters can overcome the governors expected veto.

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SME Topeka welcomes speaker connecting neuroscience to the real world - WIBW

Neuroscience

Behavioral Neuroscience Program awards pair of summer research … – Western Washington University

The Behavioral Neuroscience Program is pleased to announce the 2023 recipients of the BNS Program Undergraduate Summer Research Award and the Dr. David Goldman and Dr. Linda Blackwell Undergraduate Summer Research Award. Both research awards aim to increase opportunities in Behavioral Neuroscience research for individuals who are typically underrepresented in the field. The awards will be given annually to a Behavioral Neuroscience undergraduate with demonstrated interest in behavioral neuroscience research, enthusiasm for a graduate degree or health professional program, and has financial need.

This years BNS Program Summer Undergraduate Research Award recipient is Lauren Gilman (she/her), who works in the lab of Josh Kaplan, an associate professor in the Department of Psychology. Gilman wants to become an osteopathic psychiatrist after graduation and this summer will research cannabis effects on autism spectrum disorder.

Im thrilled that Lauren will have the opportunity to explore her research interests this summer, and Im looking forward to supporting her scientific growth as she learns new molecular approaches that will be applied to her research into cannabis effects in autism spectrum disorder," said Kaplan. "Lauren will now be able to apply her holistic approach to medicine and research by studying the effect of cannabis on the gut-brain axis, neuroinflammation, and behavior using molecular and mass spectrometry approaches. These are hot areas of research and Im excited for Lauren to lead our lab in this new direction."

Gilman was grateful for the research award and excited to get to work this summer.

"I am grateful for this award and honored to be a presence for other queer women in STEM. My time at Western has given me immense opportunities for growth and leadership. To name a few, I participated in the psychiatry internship, as the NeRDS publicity officer, as the waterski team travel coordinator, and as a volunteer in Dr. Kaplan's cannabis lab," Gilman said. "I hope my research on the microbiome and inflammation in autism spectrum disorder increases our understanding of CBD and paves the way for other safe, novel treatments."

"In the future, I hope to work as an osteopathic psychiatrist, providing a holistic approach to healing. Admittedly, many psychiatric disorders have a biological basis and require pharmacological intervention to improve symptoms; however, I plan to approach patients as people first, not as an array of dysfunctional circuits and chemicals. Environment, social connections, and underlying disease impact the minds state just as much as neurotransmitters and deserve equal attention," she said.

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Neuroscience

Data and Tools Integration in the Canadian Open Neuroscience … – Nature.com

The platform design relies on open formats, APIs, and standards to allow for extensibility and promote interoperability. The key design ideas are based on the following constraints and considerations:

The platform should integrate data resources from different infrastructures,

Data and tools should be integrated without undue duplication,

Integration of data and tools in the platform by community members should be feasible,

Datasets and processing tools should implement the FAIR principles,

Data governance should remain with the original data stewards or providers,

The platform should rely on open formats and standards to foster reuse and integration with other projects, and

The portal should provide intuitive navigation and provide users with documentation and help resources.

The CONP consists of several key components (Fig.1, see also Table4):

A data infrastructure layer, incorporating disparate independent data repositories (e.g., Zenodo, http://www.zenodo.org, LORIS7, or the Open-Science Framework OSF5);

A (meta)data integration layer, leveraging DataLad13, GitHub14, Boutiques tool descriptors12, enabling uniform data search queries based on the Data Tags Suite (DATS) model15;

An analysis layer that allows for simple download of tools and easy use of High-Performance Computing (HPC) environments; and

An interface layer, which controls the interaction between these components and will be outlined further in the Results section.

Architecture of the Canadian Open Neuroscience Platform. The platform is comprised of multiple tiers including: (i) Independent data infrastructure; (ii) Metadata integration across tools and datasets via standard models (Biocaddie DATS, Boutiques descriptors); (iii) Data analysis on High-Performance Computing and; (iv) Web and command-line interfaces.

The CONP takes advantage of distributed data repositories, each with their own infrastructures, access control requirements, APIs, and licensing. This importantly gives flexibility to manage collections using specific context-appropriate tools, rather than prescribing an incomplete one-size-fits-all solution. The CONP presently supports accessing and integrating data from several flexible domain-agnostic datastores (OSF, Zenodo, FRDR-DFDR, https://www.frdr-dfdr.ca/), specific brain imaging repositories (LORIS, XNAT, Brain-CODE), and the commonly used HTTP and FTP web protocols. This set of supported infrastructures is intentionally extensible to any other repository which allows access via programmatic web-compatible interfaces (e.g. a RESTful API).

To integrate datasets across infrastructures, the CONP uses DataLad as a backend and GitHub to host the metadata. Crawlers automate both the discovery of tools (on Zenodo, http://www.zenodo.org) and datasets (on Zenodo and OSF) and the DataLad and GitHub integration workflows. CircleCI16 continuously tests if datasets are available and if data are accessible by testing the download of a few files from the datasets.

The CONP adopts a decentralized architecture, to accommodate the various governance, ethical, and performance models required by data owners. For instance, some datasets may not easily be stored outside of the jurisdiction where they were acquired, while some institutions require local control of data storage, with some projects preferring to remain in control of access rules. This is all possible in CONP, as data can remain hosted anywhere on the internet.

Integration between datasets is provided by DataLad, a software library for managing Git repositories that references data. In DataLad, datasets are described in a Git repository containing metadata, file URLs and hashes of data blobs managed by git-annex. Importantly, a DataLad dataset does not generally contain the data themselves, which remain stored remotely. DataLad datasets can also be nested to represent dataset aggregation.

The CONP dataset consists of a main DataLad dataset and its metadata stored on GitHub (github.com/CONP-PCNO/conp-dataset) and referenced in the main DataLad index (http://datasets.datalad.org). The use of GitHub enables a variety of features useful for open-source software development; including issue tracking, code reviews, pull requests, branch protection, and integration with various applications. Datasets are integrated as Git submodules of the main dataset, and may be hosted on GitHub or on any other platform including GitLab or even a simple web server. This has the added benefit of being able to point to a specific commit, allowing continued evolution of the remote subdataset while the CONP portal keeps a reference to the stable version of the root dataset. Any DataLad dataset can be integrated into CONP provided that it contains a README file and a Data Tags Suite (DATS17) model file describing it. In addition, a configuration script can be added to the root of the dataset, to perform any required initialization.

The data themselves can be stored in any server implementing a protocol supported by git-annex, including HTTP, FTP, and many more. We used this flexibility to integrate data coming from three main types of sources. First, brain data archives such as the LORIS7, XNAT18, and Brain-CODE19 platforms provide a complete neuroscience data management solution for data ingestion, quality control, visualization, access control, and querying. They are commonly used to support large-scale multi-site longitudinal studies with hundreds of participants. Second, multi-disciplinary research data archives such as Zenodo in Europe, the Open Science Framework in the USA5, and the Federated Research Data Repository (FRDR)20 in Canada, provide simple ways to share research data publicly through the web and to guarantee long-term archival, findability, and immutability of data objects through Digital Object Identifiers (DOIs). They are typically used for local studies or companion data to a publication. Third, simple internet hosts accessible through the HTTP or FTP protocol allow for flexible integration of any other data already available online. CONP also provides local data-hosting for users who do not have the resources to make use of these other options.

Through git-annex, DataLad also supports authentication protocols, a critical feature for the ethical sharing of neuroscience data with restricted access. We extended this capability to support authentication to the LORIS, Zenodo, and OSF platforms. LORIS uses a common username/password authentication, which could be added to DataLad without particular challenges. Zenodo, however, implements private data sharing through secret tokens added to the file URLs. Since the file URLs are part of the DataLad repository and are therefore publicly shared, we implemented a custom mechanism to add and remove tokens from URLs on demand.

To leverage the capabilities of existing research data archives (currently Zenodo and OSF, and in the future FRDR), we developed a crawling framework to manage the life cycle of DataLad datasets on GitHub. As a result, users can upload datasets to the CONP through these web platforms, without having to install and learn DataLad, or to become familiar with our GitHub workflow. The CONP data crawler performs the following actions, implemented as a base class containing most of the GitHub and DataLad logic, and as a set of derived classes containing the API calls specific to each crawled platform:

Search for CONP-tagged datasets in web platforms;

When a new dataset is found, create a new DataLad dataset;

When a dataset modification is detected, update the corresponding DataLad dataset;

Push modifications to CONP forked GitHub repository;

Create a pull request for each modified dataset, for the CONP maintainers to review and approve.

In addition, if no DATS model is found in the datasets, one is created automatically from the fields available in the web platforms, with minimal information such as title, license and creators.

The CONP includes a dataset testing suite to mitigate the reliability challenges of decentralized systems. We implemented the testing suite in the CircleCI platform, due to its support for multithreaded testing, FTP connections, and interactive SSH sessions in testing environments. Hosting CONP DataLad datasets on GitHub allows for transparent integration with CircleCI. Similar to a software repository, dataset tests are triggered with every GitHub pull request, and their successful execution is required for the pull request to be approved by the maintainers. To reduce execution time, the testing framework only runs the tests for the datasets influenced by the pull request.

Datasets may become unavailable for a variety of transient reasons, including network interruptions, operational downtimes of the hosting platforms, or configuration errors. To detect these issues, we configured CircleCI to periodically test all the datasets available through the CONP every four hours, providing continuous monitoring. Results of this periodical testing are stored in CircleCI artifacts and are automatically displayed as status badges in the CONP portal. To increase robustness against transient errors, we used Pytests flaky module to re-run tests three times upon failure, with a 5-second delay.

The test suite tests the following properties for every dataset:

Presence of a README file at the root of the dataset,

Presence of a DATS model complying with our extended schema,

Successful installation of the dataset with DataLad,

Integrity of the git-annex repository, and

Successful download of the four smallest files from a sample to reduce runtime.

For datasets that require authentication, we include credentials through CircleCI environment variables. To reduce the associated security risks, we configured the testing framework to skip the testing of authenticated datasets in pull requests. From these environment variables, the testing framework generates a DataLad authentication provider (LORIS, Brain-CODE), or configures the dataset to use access credentials (Zenodo). The testing suite is executed in a Docker container also available for download to replicate the testing environment.

As the CONP portal brings together two types of research objects, software tools and datasets, we have reused two metadata standards developed to document these objects. The Boutiques standard12 describes a tools execution, inputs and outputs. We chose the Data Tags Suite (DATS) model17 developed by the BioCaddie consortium (Big Data to Knowledge NIH funds) to build the Datamed (https://datamed.org/) platform, for dataset description. Datamed was designed to be an equivalent of PubMed for datasets21, and DATS follows the architecture of the Journal Article Tag Suite JATS. This choice was driven by the flexible nature of DATS and its associated material (e.g., validator, documentation). DATS also has the capacity to represent sub-datasets, a feature that can be used in association with the DataLad sub-datasets mechanism (implemented with git submodules).

These two standards are used to extract information about the research objects to be displayed in the portal, as well as provide the necessary JSON-LD information for making the datasets discoverable by Google Dataset Search. The DATS model also allows for an RDF representation of the information, which enables integration of the CONP metadata as a knowledge graph in BlueBrain Nexus22. The portal includes an advanced search interface mapped to a BlueBrain Nexus SPARQL endpoint where the DATS model files are regularly exported.

The DATS model contains a number of required fields: the name and description of the dataset, the name and affiliation(s) of the individual(s) who generated the data, the license under which a dataset is released, keywords, and data types and formats. It may also include details regarding related publications, funding bodies, and cross-referencing derived datasets. We have also applied the extensibility of the DATS model to add specific fields such as a structured record of the datasets source, allowing searches by institution, city, or country of origin17.

The CONP portal goes beyond the findability of tools, directly integrating tools into workflows and enabling their execution on HPC systems.

Analysis tools are uniformly described in Boutiques, an open specification and software library for sharing tools according to the FAIR principles1. Boutiques descriptors are JSON objects containing a specification of the tool input data, parameters, and output data. They link to a Docker or Singularity container image where the tool and all its dependencies are installed and configured for execution. Boutiques tools can be reused in various platforms, such as workflow engines, as exemplified in TIGR-PURR (https://github.com/TIGRLab/TIGR_PURR), or in web platforms such as CBRAIN23 or VIP (https://www.creatis.insa-lyon.fr/vip/).

Boutiques tools can be published, archived, and retrieved in the Zenodo research archive or in the OpenAIRE-Nexus project. Once published, Boutiques tools receive a DOI, which makes their archives permanently findable.

Similar to the data integration layer, tools can be executed through both command-line and web interfaces. The Boutiques command-line tool can be used to run the tools locally with a uniform interface, provided that a container engine is installed. This is useful for testing analyses or processing smaller datasets. CONP datasets can be downloaded locally for processing through the DataLad command-line or Python API. Boutiques Python API also enables tool integration in external pipeline engines such as Pydra24, Nextflow25, or Apache Spark26.

For use-cases that benefit from the use of HPC clusters, the Clowdr command-line tool and Python API27 can easily be used to apply Boutiques tools concurrently to multiple subjects on HPC clusters available through the SLURM workload manager, such as the ones provided by Compute Canada (https://www.computecanada.ca/), or on the Amazon Elastic Computing Cloud (EC2). This allows CONP users to leverage their own resource allocation and to process CONP datasets through the DataLad interface.

Many CONP tools are also installed in CBRAIN23, a web portal interfaced with storage and computing resources at HPC centers, to provide a higher-level interface for users who do not want to use the command-line, or for developers who prefer to interact with HPC resources through a web API. CBRAIN can import Boutiques descriptors, and create web forms and HPC jobs to launch and monitor the tools. Pipelines that were installed as Docker images are converted to Singularity for deployment on HPC clusters. To facilitate the processing of datasets accessible via the CONP, CBRAIN also interfaces with DataLad, downloading files on-demand for processing.

Running a data analysis pipeline on CBRAIN requires a CBRAIN account. There is no current billing model associated with the compute part of the platform, because CBRAIN relies on academic computing resources, primarily Compute Canada, obtained through resource allocation competitions. The CBRAIN infrastructure allows for external compute resources to be attached to the platform such that an international research laboratory could use its own resources. CBRAIN also has a certain amount of computing time allocated on Compute Canada and when possible the team can offer these for reasonable usage. This needs to be directly requested to the CBRAIN infrastructure governance team through an email to CBRAIN support. Data derived from processing will be stored on the CBRAIN infrastructure, and the agreement by the CBRAIN team to process data will depend on both the compute time (if on CBRAIN Compute Canada allocation) and on the capacity to store these derived data. We note that CBRAIN can also attach data providers with the Principal Investigators own disk space allocation on Compute Canada, on other accessible infrastructures, or even on their own laboratory servers. Given the variety of situations, requests for compute time and disk space are handled on a case by case basis.

Finally, Boutiques executions, including local, Clowdr and CBRAIN ones, also collect anonymized provenance records for activity monitoring, traceability, and other applications.

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Neuroscience

The Neuroscience of Learning – New Trader U

The neuroscience study opens new avenues for understanding the brains role in learning and education. As researchers uncover more about the mechanisms underlying acquiring knowledge, educators can implement evidence-based strategies to enhance student outcomes. This blog post delves into the fascinating world of neuroscience, explores how the brain learns, and examines various learning theories and strategies informed by neuroscientific research.

Neuroscience refers to studying the nervous system, focusing on its role in behavior, cognition, and learning. The human brain, a complex organ, contains billions of neurons that transmit information through electrical and chemical signals. These neurons form networks, and the brains organization into different regions allows it to carry out specific functions.

Learning involves three primary processes: encoding, consolidation, and retrieval. The brain processes new information during encoding, while consolidation refers to stabilizing memories. Retrieval, on the other hand, involves recalling information from memory. Several brain regions, including the prefrontal cortex, hippocampus, and amygdala, contribute to these processes. The prefrontal cortex plays a role in decision-making, problem-solving, and critical thinking, while the hippocampus is essential for forming new memories. The amygdala is responsible for emotional processing and memory consolidation.

Neuronal plasticity, the brains ability to change and adapt due to experience, is critical to learning. Synaptic plasticity involves changes in the strength of connections between neurons, and neurogenesis refers to the formation of new neurons. Both of these processes contribute to the brains adaptability and capacity for learning.

Cognitive learning theories focus on the mental processes involved in learning. One such theory, the Information Processing Theory, likens the brain to a computer. According to this theory, information passes through three stages: sensory memory, short-term memory, and long-term memory. Another cognitive learning theory, Cognitive Load Theory, emphasizes working memory capacity limits. Effective learning requires managing cognitive load to prevent overloading.

Neuroscience research has identified several effective learning strategies, including retrieval practice, spaced repetition, and interleaving. Retrieval practice involves actively recalling information from memory, which has been shown to strengthen memory and improve long-term retention. Spaced repetition refers to revisiting material at increasingly longer intervals, a technique proven to enhance memory consolidation and retention. Interleaving involves mixing different topics or types of problems during study sessions, which can enhance cognitive flexibility and promote the better transfer of learning.

The amygdala plays a significant role in learning, processing emotional stimuli, and connecting them to memories. Emotional regulation, or the ability to manage emotions, can impact cognitive processes and learning outcomes. Chronic stress can impair memory and cognitive function, making it essential to develop strategies to reduce stress and promote a positive learning environment.

Learning disabilities are neurodevelopmental disorders that affect the brains ability to process information. Individuals with learning disabilities exhibit structural and functional differences in language, memory, and attention-related brain regions. Strategies for supporting individuals with learning disabilities include personalized learning plans, assistive technologies, and support from educators, therapists, and specialists.

The potential of neuroscientific research in education is immense. As researchers continue to expand our understanding of how learning occurs, educators can integrate these findings into evidence-based teaching strategies. Identifying individual learning preferences and needs can lead to more personalized educational experiences.

Technology also plays a role in the intersection of neuroscience and education. Neuroimaging techniques like functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) allow researchers to study learning processes in real-time. Brain-computer interfaces and adaptive learning technologies hold promise for developing personalized learning experiences. Virtual reality and immersive learning environments can also provide unique educational opportunities that engage students on a deeper level.

Ethical considerations must be addressed in applying neuroscience to education. Balancing the benefits and potential risks of using neuroscientific data in educational settings is crucial. Issues of privacy, consent, and data security must be considered.

The field of neuroscience offers valuable insights into the brains role in learning and education. Educators can implement evidence-based strategies to enhance student outcomes by understanding the underlying learning mechanisms. Cognitive learning theories, such as Information Processing Theory and Cognitive Load Theory, can provide a framework for understanding the mental processes involved in learning.

Neuroscientific research has also informed effective learning strategies, such as retrieval practice, spaced repetition, and interleaving. These strategies have improved memory consolidation, retention, and cognitive flexibility. Additionally, understanding the impact of emotion on learning and the neuroscience of learning disabilities can help educators develop targeted support strategies for students with diverse needs.

As the field of neuroscience continues to grow, so too will its potential applications in education. Technology, including neuroimaging techniques and virtual reality, will undoubtedly play an increasingly important role in understanding and enhancing learning experiences. However, it is essential to address ethical considerations to ensure that these advancements benefit all students and protect their privacy and rights.

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The Neuroscience of Learning - New Trader U

Neuroscience

CMU Neuroscience Major Researches Mindfulness Meditation – News – Carnegie Mellon University

Aiwen Chen remembers the stress of studying for the college entrance exam as a high school student in China, and the impact it had on her and her friends.

"That's why I'm very interested in stress management, because a lot of my friends were in this same, extremely stressful situation, and a lot of them were having mental health issues," Chen said. "It becomes such a heavy burden."

Chen, a Carnegie Mellon University junior with a major in neuroscience(opens in new window) and an additional major in philosophy(opens in new window) in the Dietrich College of Humanities and Social Sciences(opens in new window), was the recipient of a Summer Undergraduate Research Fellowship(opens in new window) (SURF) award that allowed her to conduct research on the effects of mindfulness meditation on stress levels. She was part of a team working to determine the correct dosage of meditation a person needs for optimal results.

Her research was based on the Monitor and Acceptance theory of mindfulness training, which posits that people can be trained to achieve a state of mindfulness in meditation by learning how to experience and better monitor the present moment, with an attitude of acceptance. Participants in the research took 20-minute lessons daily for 14 days.

Her somewhat unusual combination of majors was possible because CMU encourages interdisciplinary learning. "It's like multiple programs or multiple displays intertwine with each other," Chen said. It was this encouragement to study across fields that helped Chen decide on philosophy as her additional major because she said it complements the work she does in her neuroscience major.

"I'm super interested in the brain, how it works and how the physiology of the brain impacts psychological effects in humans," she said. "I'm very interested in the problems of mind and body and how philosophers approach those questions."

Chen said the SURF award allowed her to get hands-on experience, the kind she was hoping for when she decided to attend CMU. "I really wanted to know how research is conducted, the whole process of doing research from scratch," she said.

Her graduate student mentor, Asal Yunusova, helped her learn how to tackle problems and improve her study management and communication skills. Yunusova said that Chen showed great initiative and thought like a research scientist.

J. David Creswell,(opens in new window) the William S. Dietrich II Professor in Psychology, worked with Chen to come up with her core project design of assigning study participants to either zero, seven or 14-day programs, to examine the stress tolerance outcomes.

Aiwen has been building some really innovative research focused on answering just how much meditation training dose is needed for benefits, which is a largely unanswered question in the field. It has been a lot of fun for me to collaborate with her on this work, Creswell said.

Aiwen was very detail-oriented and thoughtful when conducting her research project, Yusunova said. And she worked very diligently putting together on the various experiment scripts and survey measures that we would be administering, and was very diligent with recruiting and running in-person sessions.

Aiwen said shes still trying to decide what she wants to do after she completes her undergraduate study. She is considering possibly going to medical school to be a psychiatrist, or enter a graduate program for clinical psychology to be a therapist.

I want to work in mental health, she said, to best help people relieve the pain of their mental health issues.

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CMU Neuroscience Major Researches Mindfulness Meditation - News - Carnegie Mellon University

Neuroscience

Using Photons as Neurotransmitters to Control the Activity of Neurons – Neuroscience News

Summary: Researchers present a new system that uses photons instead of chemical neurotransmitters to control neural activity.

Source: ICFO

Our brains are made of billions of neurons, which are connected forming complex networks. They communicate between themselves by sending electrical signals, known as action potentials, and chemical signals, known as neurotransmitters, in a process called synaptic transmission.

Chemical neurotransmitters are released from one neuron, diffuse to the others and arrive at the targeted cells, generating a signal which excites, inhibits or modulates the cellular activity. The timing and strength of these signals are crucial for the brain to process and interpret sensory information, make decisions, and generate behavior.

Controlling the connections between the neurons would allow us to understand and treat better neurological disorders, rewire or repair the malfunctions of the neural circuits after being damaged, improve our learning capabilities or expand our set of behaviours. There are several approaches to controlling neuronal activity.

One possible method is using drugs, that alter the levels of the chemical neurotransmitters in the brain and affect the activity of neurons. Another approach is to use electrical stimulation applied to specific brain regions to activate or inhibit the neurons. A third possibility is using light to control neural activity.

Using photons to control the neuronal activity

Using light to manipulate neuronal activity is a relatively new technique that has been explored in the past. It involves genetically modifying neurons to express light-sensitive proteins, ion channels, pumps or specific enzymes in the target cells. This technique allows researchers to precisely control the activity of concrete populations of neurons with higher precision.

There are, however, some limitations. It needs to be delivered very close to the neurons to achieve enough resolution at the level of the synapsis, as light scatters in the brain tissue. Thus, it is often invasive, requiring external interventions. Moreover, the intensity needed to reach the targeted cells can be potentially harmful to them.

To overcome these challenges, a team of ICFO researchers presents inNature Methodsa system that uses photons instead of chemical neurotransmitters as a strategy to control neuronal activity.

The ICFO researchersMontserrat Porta,Adriana Carolina Gonzlez,Neus Sanfeliu-Cerdn,Shadi Karimi,Nawaphat Malaiwong,Aleksandra Pidde,Luis Felipe MoralesandSara Gonzlez-Bolvarled byProf. Michael Kriegtogether withPablo FernndezandCedric Hurth, have developed a method to connect two neurons by using luciferases, light-emitting enzymes, and light-sensitive ion channels.

They have developed and tested a system named PhAST -short for Photons as synaptic transmitters- in the roundwormCaenorhabditis elegans, a model organism widely used to study specific biological processes. Resembling how the bioluminescent animals use photons to communicate, PhAST uses the enzymes luciferases to send photons, instead of chemicals, as transmitters between neurons.

Replacing chemical neurotransmitters with photons

To test if photons could codify and transmit the activity state between two neurons, the team genetically modified the roundworms to have faulty neurotransmitters, making them insensitive to mechanical stimuli. They aimed to overcome those defects using the PhAST system. Secondly, they engineered light-emitting enzymes luciferases and selected ion channels that were sensitive to light.

To follow the information flow, they developed a device that delivered mechanical stresses to the animals nose while measuring, at the same time, the calcium activity in the sensory neurons, one of the most important ions and intracellular messengers.

To be able to see the photons and study bioluminescence, the team had previously designed a new microscope by simplifying a fluorescence one, removing all the unnecessary optical elements such as filters, mirrors, or the laser itself, assisted with machine learning to reduce the noise coming from the external sources of light.

Researchers then tested that the PhAST system worked in several experiments and succeeded in using photons to transmit neuronal states. They were able to establish a new transmission between two unconnected cells, restoring neuronal communication in a defective circuit.

They also suppressed the animals response to a painful stimulus, changed their response to an olfactory stimulus from attractive to aversive behavior and studied the calcium dynamics when laying the eggs.

These results demonstrate that photons can indeed act as neurotransmitters and allow communication between neurons and that the PhAST system allows the synthetic modification of animal behavior.

The potential of light as a messenger

Light as a messenger offers a broad scope for future potential applications. As photons can be used in other types of cells and several animal species, it has wide-ranging implications for both basic research and clinical applications in neuroscience.

Using light to control and monitor neuronal activity can help researchers better understand the underlying mechanisms of brain function and complex behaviors, and how different brain regions communicate with each other, providing new ways of imaging and mapping brain activity with higher spatial and temporal resolution. It could also help researchers develop new treatments, and for example, be useful for repairing damaged brain connections without invasive surgeries.

However, there are still some limitations to the widespread use of the technology, and further improvements in the engineering of the bioluminescent enzymes and the ion channels or in the targeting of molecules would allow controlling optically the neuronal function, non-invasively and with higher specificity and precision.

Author: Alina HirschmannSource: ICFOContact: Alina Hirschmann ICFOImage: The image is credited to ICFO

Original Research: Closed access.Neural engineering with photons as synaptic transmitters by Montserrat Porta-de-la-Riva et al. Nature Methods

Abstract

Neural engineering with photons as synaptic transmitters

Neuronal computation is achieved through connections of individual neurons into a larger network. To expand the repertoire of endogenous cellular communication, we developed a synthetic, photon-assisted synaptic transmission (PhAST) system.

PhAST is based on luciferases and channelrhodopsins that enable the transmission of a neuronal state across space, using photons as neurotransmitters.

PhAST overcomes synaptic barriers and rescues the behavioral deficit of a glutamate mutant with conditional, calcium-triggered photon emission between two neurons of theCaenorhabditis elegansnociceptive avoidance circuit.

To demonstrate versatility and flexibility, we generated de novo synaptic transmission between two unconnected cells in a sexually dimorphic neuronal circuit, suppressed endogenous nocifensive response through activation of an anion channelrhodopsin and switched attractive to aversive behavior in an olfactory circuit.

Finally, we applied PhAST to dissect the calcium dynamics of the temporal pattern generator in a motor circuit for ovipositioning. In summary, we established photon-based synaptic transmission that facilitates the modification of animal behavior.

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Using Photons as Neurotransmitters to Control the Activity of Neurons - Neuroscience News