Category Archives: Neuroscience

Neuroscience

Shape Therapeutics enters into a strategic research

SEATTLE, Aug. 24, 2021 (GLOBE NEWSWIRE) -- Shape Therapeutics Inc. (ShapeTX), a biotechnology company developing RNA technologies to shape the future of gene therapy, today announced a multi-target strategic collaboration and license agreement with Roche (SIX: RO, ROG; OTCQX: RHHBY). Through this partnership ShapeTX will apply its proprietary RNA editing platform RNAfixand potentially leverage its AAVidtechnology platform for next-generation tissue-specific adeno-associated viruses (AAVs) for the development of gene therapy for certain targets in the areas of Alzheimers disease, Parkinsons disease, and rare diseases.

During the course of the partnership, ShapeTX will conduct preclinical research to identify and deliver development candidates discovered by its AI-powered platforms RNAfixand, potentially, AAVid. Roche will be responsible for the development and worldwide commercialization of any potential products resulting from the collaboration.

Our mission at ShapeTX is to unlock the next breakthrough in RNA technologies in the gene therapy space across a wide range of therapeutic areas, said Francois Vigneault, PhD, co-founder and Chief Executive Officer of ShapeTX. The relationship with Roche quickly centered on a common desire to tackle some of the worlds most challenging diseases by accelerating the development of breakthrough technologies towards the clinic.

We are excited by the disruptive potential of ShapeTXs RNA-editing approach based on natures own mechanism for specific base editing. This new collaboration is also perfectly aligned with our broader efforts across the Roche Group to unlock the full potential of gene therapy, said James Sabry, Head of Roche Pharma Partnering. We look forward to working with ShapeTX to create novel treatment options for neuroscience and rare disease indications.

Under the terms of the agreement, ShapeTX is eligible to receive an initial payment as well as development, regulatory and sales milestone payments, potentially exceeding $3 billion in aggregate value. ShapeTX is also eligible to receive tiered royalties on future sales of products resulting from the collaboration.

About Shape Therapeutics Inc.Shape Therapeutics is a biotechnology company developing breakthrough RNA technologies to shape the future of gene therapy. The ShapeTX gene therapy platform is comprised of RNAskip, RNAfixand RNAswappayload technologies, next-generation tissue-specific AAViddelivery technology, and SquareBio, a solution for scalable gene therapy manufacturing based on industrialization of human stable cell lines. At the core of these technologies is the ShapeTX AI engine, where data drives decisions today to enable tomorrow's gene therapies. ShapeTX is committed to data-driven scientific advancement, passionate people, and a mission of providing lifelong cures to patients. Shape Life! shapetx.com

Contact Business Contact:Shape Therapeutics Inc.Cindy Fung, PhDcindy@shapetx.com

Media Contact:ID Public RelationsLydia Youmedia@shapetx.com

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Shape Therapeutics enters into a strategic research

Neuroscience

The Facts on ALS – Articles and Videos, Featured, Health Topics, Neuroscience – Hackensack Meridian Health

October 11, 2021

ALS, or amyotrophic lateral sclerosis, is a debilitating disease that affects motor nerve cells in the brain and spinal cord. This causes a wide variety of symptoms, but most commonly and universally, people with ALS experience progressive muscle weakening and paralysis. As many as 30,000 people in the United States have ALS, and about 5,000 new cases are diagnosed every year.

You may have heard of ALS due to the Ice Bucket Challenge, or even as its previously common name, Lou Gehrigs disease. Here are answers to some of the most common questions asked about ALS.

No. Unfortunately there is no way to prevent ALS, says Mary Sedarous, M.D., neuromuscular medicine specialist and director of the ALS Center at Jersey Shore University Medical Center and assistant professor, Department of Neurology, Hackensack Meridian School of Medicine. For many people with ALS, there is not even a clear identifying cause of the disease. Researchers have studied numerous potential causes, such as diet, lifestyle and environment, among others. However, to this date, no clear reason has been identified.

For other patients with ALS, the cause is genetic. For about 5 to 10 percent of people with ALS, there is a clear genetic line to another family member with ALS. This is called familial ALS.

Genetic testing can be done for ALS, says Dr. Sedarous. I recommend discussing your options with a genetic counselor before undergoing the testing process.

Because there is no clear identifying cause for many cases of ALS, it is difficult to pinpoint risk factors, says neurologist Florian Thomas, M.D., Ph.D., co-director of the ALS Center and professor and founding Chair, Department of Neurology, Hackensack University Medical Center and Hackensack Meridian School of Medicine. Dr. Thomas explains that the clearest risk factor is having a family history of ALS.

That being said, Dr. Thomas points to some other factors to consider:

It is hard to say. Currently there is no cure for ALS, but that is not due to lack of effort from doctors and researchers.

Research is ongoing, and treatments and medications that help slow the effects of ALS are continually being discovered, says Dr. Thomas. Today, ALS treatment is an interprofessional undertaking that includes respiratory support, medication, physical therapy, speech therapy, assistive devices and other forms of treatment and support. And at Hackensack, we are pursuing a small, phase 1 study that seeks to show that re-educating the bone marrow to produce less neuro-inflammation may be helpful in ALS.

The material provided through HealthU is intended to be used as general information only and should not replace the advice of your physician. Always consult your physician for individual care.

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The Facts on ALS - Articles and Videos, Featured, Health Topics, Neuroscience - Hackensack Meridian Health

Neuroscience

Meet Neumora, Arch’s $500M, Amgen-partnered play for the targeted future of neuroscience R&D – FierceBiotech

Arch Venture Partners has taken the lid off its big bet on neuroscience. Having quietly put the startup together over the past 18 months, Thursday Arch unveiled Neumora Therapeuticsa biotech that starts life with $500 million, a collaboration with Amgen and a pipeline of eight prospects.

Neumora represents a test of the idea that neuroscience is on the cusp of the sort of rapid progress that has transformed oncology in recent years. If Neumora is right, recent advances in genomics and neurobiology have set the stage for more targeted modulation of the underlying biology of specific brain diseases, just as the oncology field has gone from targeting organs to zeroing in on molecularly defined diseases.

We recognized an opportunity to build a proprietary toolbox of state-of-the-art neural network technologies, which uniquely positions us to pioneer a new era in precision medicines for brain diseases by integrating data science and neuroscience, Lori Lyons-Williams, chief operating officer at Neumora, said.

Armed with the platform, Neumora aims to match the right patients to targeted therapeutics, Lyons-Williams said, enabling it to de-risk clinical trials and improve outcomes for patients. Unlike most newly unveiled biotechs, Neumora is already in a position to start putting its ideas to the test in the clinic.

RELATED: As Amgen zeroes in on cancer, neuroscience pipeline under the ax

The startup begins life with a pipeline of eight candidates, two of which are in the clinic, and more than $500 million to fund their development. Most of the money comes from an Arch-led syndicate.

Some of the assets, targeting casein kinase 1 delta and glucocerebrosidase, and $100 million of the cash come from Amgen, which pulled out of neuroscience R&D in 2019. The Big Biotechs retreat from the hard-to-crack therapeutic area opened the door to a deal with Neumora. Amgen will use its deCODE genetics and human data research capabilities to feed insights into Neumoras precision neuroscience platform.

Neumora put together the rest of the pipeline by rolling up privately held companies including BlackThorn Therapeutics. Arch led a $40 million series A round in BlackThorn in 2016 and went on to participate in a $76 million series B in 2019. The rounds positioned BlackThorn, under the leadership of a team featuring Paul Berns, to advance targeted therapeutics for mental health.

BlackThorn is now part of Neumora, and Berns is CEO of the combined company, slotting in at the head of a C-suite that features John Dunlop, Ph.D., formerly of Amgen, in the chief scientific officer role. Other posts are filled by former employees of companies including Alexion and BlackThorn. As it stands, BlackThorn is still listed as the sponsor of a phase 2 clinical trial that is testing kappa opioid receptor antagonist BTRX-335140 in patients with major depressive disorder. The 180-subject study is scheduled to wrap up next summer, according to ClinicalTrials.gov.

RELATED: Fierce 15 2017 | BlackThorn Therapeutics

BTRX-335140, now known as NMRA-140, is joined in Neumoras clinical-phase pipeline by NMRA-511, a selective V1aR antagonist that is in phase 1 development as a treatment of anxiety disorders. Neumoras preclinical pipeline addresses sleep, neuropsychiatric and neurodegenerative disorders.

Building a pipeline that has mental health programs alongside drugs targeting neurodegenerative diseases sets Neumora apart from most of its predecessors. However, while acknowledging that the industry has historically kept neuropsychiatric disorders and neurodegenerative diseases separate, Lyons-Williams thinks current knowledge supports a more unified approach.

The reality is that these are all diseases of one organ, the brain, and there are mechanistic overlaps and comorbidities across these diseases. We believe our multi-modal data science approach captures unique insights across a range of disease drivers including genetic, imaging and clinical that can be applicable across brain diseases, Lyons-Williams said.

Neumora will soon be in a position to start delivering some early wins, or losses. Data drops on the two clinical programs are planned for 2022 and 2023, Lyons-Williams said, and multiple INDs are on the schedule for the next few years. Neumora plans to advance the pipeline prospects while building out its platform, including by adding more data sets and expanding its data science efforts.

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Meet Neumora, Arch's $500M, Amgen-partnered play for the targeted future of neuroscience R&D - FierceBiotech

Neuroscience

Research Fellow, Imaging/Cognitive Neuroscience job with ROYAL HOLLOWAY, UNIVERSITY OF LONDON | 268065 – Times Higher Education (THE)

Department of Psychology

Location: EghamSalary: 36,438 to 38,516 per annum - including London AllowancePostType: Full TimeClosingDate: 23.59 hours GMT on Monday 01 November 2021Reference: 0921-345

Full-Time, Fixed-Term

Applications are invited for the post of Research Fellow in the Psychology Department.

We are seeking an enthusiastic, productive and highly-skilled early-career scientist for a postdoctoral research position linked to a recently awarded BBSRC grant held jointly across Royal Holloway, University of London, and Cardiff University (e.g., Cardiff University Brain Research Imaging Centre, CUBRIC). This exciting project will apply state-of-the-art 7-Tesla MRI (and connectom diffusion MRI) to examine the functional neuroanatomy and connectivity of the human subiculum and broader hippocampal network. The studies will focus primarily on the fine-grained mapping of hippocampal network connectivity, as well as developing novel naturalistic cognitive paradigms to examine how the subiculum constructs representations of scenes and events.

The successful candidate will join a multi-disciplinary research team across Royal Holloway and Cardiff University and will be expected to work closely with a second postdoctoral researcher based at CUBRIC. This will include conceptualisation, implementation, design/analysis and dissemination of multimodal neuroimaging studies, as well as other activities linked to the grant (e.g., arranging regular online meetings, public engagement, supporting early-career researchers/students). The post-holder will also be expected to spend time at the partner institution when feasible. In line with our commitment to open science, they will be expected to implement reliable, reproducible, and efficient approaches to data management, thus ensuring the long-term value of these data for the wider neuroimaging community. There will also be the opportunity to analyse existing in-house and publicly available multimodal imaging datasets across human and nonhuman primates (structural/diffusion MRI, 3T/7T resting and task-fMRI). The research fellow will be expected to provide mentorship and support to junior researchers and students in the team on imaging data analyses.

Successful applicants will have a Ph.D. in cognitive/imaging neuroscience, experimental psychology, or related field (e.g., computational neuroscience or computer science). Strong skills in advanced statistical methods (e.g., MVPA, intersubject correlation analysis and/or network analyses), manuscript preparation, and working closely with other institutions are essential. A primary interest in the neuroscience of memory and spatial navigation and/or the analysis of existing large-sample datasets is desirable.

This full-time position is available to start as soon as possible. This is a fixed-term post until 30/09/2024.

Informal enquiries may be made to Dr Carl Hodgetts (carl.hodgetts@rhul.ac.uk) or Prof Andrew Lawrence (lawrencead@cardiff.ac.uk) and more information about the project can be found here:https://gtr.ukri.org/projects?ref=BB%2FV010549%2F1.

To find out more about Dr Carl Hodgetts Connected Memory Lab at Royal Holloway, please visitwww.connectedmemorylab.com. You can also visit the websites ofProf Andrew Lawrence(co-PI),Dr Jiaxiang Zhang,Prof Kim Graham, andProf John Aggletonto find out more about the work of the co-investigators.

In return we offer a highly competitive rewards and benefits package including:

The post is based in Egham, Surrey where the College is situated in a beautiful, leafy campus near to Windsor Great Park and within commuting distance from London. As described above, the post will also require the research fellow to some spend time at Cardiff University for research activities such as data collection and project meetings.

To view further details of this post and to apply please visithttps://jobs.royalholloway.ac.uk. For queries on the application process the Human Resources Department can be contacted by email at:recruitment@rhul.ac.uk

Facilities

The Psychology Department, located in Egham, close to Central London, has an excellent research profile (rated 6th in the latest Research Excellence Framework) and benefits from state-of-the-art research facilities (e.g. MRI, TMS, EEG, cognitive behavioural testing suites, Babylab). Data collection and regular meetings will take place at the Cardiff University Brain Research Imaging Centre (CUBRIC), which houses a unique combination of state-of-the-art facilities and world-leading expertise, with 4 human MRI systems (2 x Siemens Prisma, 1 x Siemens Connectom, 1 x Siemens 7T), MEG, EEG, TMS, tDCS, clinical research units and testing labs. Further details of CUBRIC can be found on their webpage (http://sites.cardiff.ac.uk/cubric).

Please quote the reference: 0921-345

Closing Date: Midnight, 1st November 2021

Interview Date: TBC

Furtherdetails: JobDescription PersonSpecification

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Research Fellow, Imaging/Cognitive Neuroscience job with ROYAL HOLLOWAY, UNIVERSITY OF LONDON | 268065 - Times Higher Education (THE)

Neuroscience

The 6 best habits to keep your brain fit, according to neuroscience – BBC Science Focus Magazine

If youve ever had the feeling that you arent as sharp as you used to be perhaps you get frustrated that you cant put a name to an actor or politician who has been in the news, for instance, or maybe youre not as quick at mental arithmetic as you were it might have given you pause for thought about your brains fitness and whether its all downhill from here.

Its true that the brain typically finishes developing in our twenties, after which there is a gradual cognitive slowing with age, so its good to start thinking about these things early. Later in life, there is also the risk of dementia, caused by diseases such as Alzheimers; inevitably, countries with ageing populations are now witnessing rising rates of dementia.

Thankfully, however, rates of cognitive slowing and dementia risk are both influenced by what experts call modifiable risk factors. In short, theres reason to be optimistic because there are things you can do lifestyle habits you can adopt to maintain your brain sharpness and protect yourself from risk of dementia.

Stay mentally active to build your cognitive reserve

Psychologists and gerontologists refer to a concept known as cognitive reserve which is essentially your brains ability to adapt in the face of ageing or illness.

For instance, if a person has high cognitive reserve, then even if they show some of the biological markers of Alzheimers (such as the clumps of protein that accumulate and harm brain function), its possible they will still perform well on tests of their mental performance. Its as if they have spare mental capacity that allows them to cope with the damage.

Importantly, there are many activities you can adopt that are considered to build your cognitive reserve, such as reading, playing musical instruments or singing, completing challenging puzzles, learning a second language and travelling. Put simply, there really is truth to the old adage to use it or lose it.

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Socialising is the ultimate brain-training activity Getty Images

You will have seen the computerised brain training games that purport to keep your grey matter razor-sharp. The problem with these games is that their benefits dont generalise youll get better at the games, but you wont see your gains spill over into other aspects of your life. The games might even be harmful if playing them to excess diverts you from socialising with friends and family. Thats because socialising is the ultimate brain-training activity.

Conversely, social isolation is considered a major risk factor for dementia. As a team of researchers at the University of Groningen put it in their recent comprehensive review of this topic, people with less social participation, less frequent social contact and more feelings of loneliness have an increased risk to develop dementia.

So, seek out company and lively conversation when you can it will give your brain a great work-out and the feelings of belonging will be a boon for your mental health too. If youre not sure where to start, try volunteering or join a debating club.

A sedentary lifestyle can speed up cognitive decline Getty Images

Your brain depends on oxygen and other nutrients to function well and so it follows that the better your cardiovascular health, the fitter and healthier your brain will be too. At the same time, a sedentary lifestyle and obesity are both associated with speedier cognitive decline and increased risk of dementia.

So, try to build an active lifestyle into your routine. Regular running, cycling, swimming or similar exercise classes will do the trick, but if thats not your thing, you could try simply walking and taking the stairs more often, or staying more active through gardening or regularly completing some other kind of hobby that gets your heart pumping, such as choir singing.

The Mediterranean diet can provide your brain with the nutrients it needs to stay healthy Getty Images

Its also good for your brain if you can sustain a healthy diet. Avoiding too much saturated fat will stop your arteries becoming clogged, and plenty of fruits and green vegetables will provide your body with ample antioxidants that help cleanse the brain of free radicals a kind of harmful by-product of various biological processes.

To meet these goals, the World Health Organization recommends the so-called Mediterranean Diet, which is high in fruit, vegetables, legumes (such as lentils, beans and peas), nuts, cereals and olive oil, while being low in saturated fats and meat. If thats too overwhelming, make a start by aiming to eat one more item of fruit a day and avoiding too many supermarket ready meals.

More surprisingly perhaps, there are also links between personality and brain health. People who score higher in Openness to Experience (one of the so-called Big Five traits thats associated with curiosity, creativity and a willingness to try out new things) tend to be sharper and at lower risk of dementia. As a team at the University of Georgia put it, Higher Openness was related to better psychomotor speed, cognitive flexibility, and working memory in depressed and non-depressed older adults.

Fortunately there are habits you can adopt to boost your Openness to Experience, such as seeking out more awe (for example by taking walks in stunning surroundings or watching nature documentaries), travelling to exotic and unfamiliar places, and enjoying mind-expanding cultural experiences (such as live theatre).

Thinking positively is the final piece of the jigsaw Getty Images

Hopefully by now, once youve established this range of positive habits around being mentally and physically active, socialising plenty, being open-minded and eating well, youll be feeling pretty optimistic about your brains future, especially as you get older. This is actually the final piece of the jigsaw.

A growing amount of research suggests that your attitudes toward ageing can have real consequences for your neural health. If you expect to become increasingly slow and prone to forgetfulness, that could well become a self-fulfilling prophecy.

Alternatively, if you realise that your brain health is to some extent in your own hands, and thats its possible with the right lifestyle and routines to remain mentally agile through life, then that is actually likely to benefit your brain.

So, seek out positive older role models if you can, take the advice in this article to heart, and seize the chance to train your brain like a muscle you may yet unlock your full potential.

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The 6 best habits to keep your brain fit, according to neuroscience - BBC Science Focus Magazine

Neuroscience

Linking mysteries of neuroscience with caring for mental health | Opinion – Sun Sentinel

These collaborations are essential to overcoming the disparities between physical and mental health care and creating a movement for understanding that taking care of our brains is just as important as taking care of our bodies. Its a movement we co-created with community partners, research institutes, theSouth Florida Science Center and AquariumandFlorida Atlantic Universitys Stiles-Nicholson Brain Instituteover the past five years through the annualTrain the Braincampaign.Train the Brain, Connecting Brain Science, Community & Care, is offering the last of two virtual educational events featuring Amishi Jha, Ph.D., professor of psychology at the University of Miami and director of Contemplative Neuroscience for the Mindfulness Research and Practice Initiative, at 1 p.m. Oct. 19.

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Linking mysteries of neuroscience with caring for mental health | Opinion - Sun Sentinel

Neuroscience

A Collection of Essays Considers Resonance in the Arts – Columbia University

Q. What is artistic resonance, and how does the concept create pathways between artistic forms and/or academic fields?

A. In my search for the most basic task of the theater experience, I came to understand that it is resonance that matters most. Our job as theater artists is to create the conditions in which resonanceliterally, vibrationcan happen between actors and the audiences bodies, minds, and senses. As I studied the phenomena of resonance, I realized that, in fact, all the arts are only as successful as the resonance that they generate with those on the receiving end.

Q. What are you most looking forward to seeing during New York's fall cultural season? Will you attend live theater?

A. I am trepidatious about being in packed rooms, but I shall tread carefully back to live performance. I am finished with Zoom performances. I am looking forward to Bill T. Jones production ofDeep Blue Seaat the Park Avenue Armory. Also,Pass OverandDana H.andIs This a Roomon Broadway.

Q. What is the last great book you read, and why?

A. I am currently enjoying Louis MenandsThe Free World. Also,The Extended Mind: The Power of Thinking Outside the Brainby Annie Murphy Paul was a complete revelation this summer and a delightful book of highly readable neuroscience.

Q. What's on your night table to read next?

A. I am reading a great deal about the poets in Russia who were highly influential prior to the Russian Revolution. These include Anna Akhmatova, Marina Tsvetaeva, Alexander Blok, Osip Mandelstam, Sergei Yesenin, Velimir Khlebnikov, and Vladimir Mayakovsky. This delicious reading is research for a project that I am directing entitledBeautiful Lady, a musical by Elizabeth Swados and Paul Schmitt.

Q. What are you teaching this semester?

A. I am teaching four classes:Directing 1 is essentially a composition class in which first-year directing students produce one short play per week.For the second-year directing students, I am co-teaching Collaboration 2 with David Henry Hwang and Christian Parker. I am also teaching a Visiting Artists course in which illustrious theater professionals come to our class each week. And along with Brian Kulick, I am co-teaching a class with New York University design professors in which our directing students work with NYU set, lighting, and costume designer students.

Q. You're hosting a dinner party. Which three scholars or academics, dead or alive, would you invite, and why?

A. bell hooks, Steven Pinker, and Oliver Sacks. What would happen then?

Check out Booksto learn more about publicationsby Columbia professors.

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A Collection of Essays Considers Resonance in the Arts - Columbia University

Neuroscience

Researchers aim to understand COVID-19 in children with Intellectual and Developmental Disabilities – URMC

Researchers at the Del Monte Institute for Neuroscience at the University of Rochester are working to better understand how COVID-19 impacts student and staff in schools that serve students with intellectual and developmental disabilities (IDD). The $4 million project, funded by the National Institutes of Health (NIH) Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP), will allow researchers to work with students and staff at the Mary Cariola Center School in Rochester, to study how COVID-19 spreads in the vulnerable population the agency serves.

Understanding how to best test this population and how COVID spreads in group settings is imperative to keeping those with an IDD safe, John Foxe, Ph.D., Director of the Del Monte Institute for Neuroscience, and co-principal investigator of the study. Ultimately, this study will have major implications for schools across the United States and specifically for schools that serve vulnerable students. This funding continues a well-establish collaboration with Mary Cariola Center and will help keep their population, many of which are too young to be vaccinated, safe from COVID.

John Foxe, Ph.D., announces study at Mary Cariola Center during press conference.

Foxe is one of three principal investigators leading this study. Martin Zand, M.D., Ph.D., co-director of Clinical & Translational Science Institute and Senior Associate Dean for Clinical Research at the Medical Center, and Stephen Dewhurst, Ph.D., Vice Dean for Research at the School of Medicine and Dentistry, are also principal investigators.

According to the NIH, a non-vaccinated person with intellectual and developmental disabilities is four-times more likely to contract COVID-19 and eight-times more likely to die from the virus than someone without an IDD. It is also a population that is difficult to test with effective procedures. This study will allow researchers to rapidly identify initial infections, antigen levels, and through isolating and contact-tracing, stop the spread of infection in school settings.

COVID-19 poses a considerable threat to our students who have intellectual and developmental disabilities as well as medical complexities, said Karen Zandi, LCSW-R, President/CEO of Mary Cariola Center. This partnership will provide crucial insight into this deadly virus and will allow us to update, revise, and create best practices beyond what we are currently doing. Ultimately, it means we will be able to keep our students and staff healthy and provide peace-of-mind to their families, while providing important research data to help schools in general and other schools like ours.

Individuals living with intellectual developmental disabilities remain disproportionately impacted by the COVID-19 pandemic, and we cannot leave them behind as we build toward our recovery, said Rep. Joe Morelle. With this study, we will be able to better combat the virus and deliver the outcomes IDD individuals across our nation and their families deserve. Thank you to the Mary Cariola Center and the University of Rochester for the incredible work you have already completed in this space and will continue to do to uplift our entire community.

In addition to researchers testing on all three Mary Cariola School campuses, they will also utilize a dedicated vehicle to travel between the school and students' homes to test and track anyone who tests positive.

Last spring, the NIH designated the Del Monte Institute for Neuroscience as one of 16 Intellectual and Developmental Disabilities Research Centers in the county.

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Researchers aim to understand COVID-19 in children with Intellectual and Developmental Disabilities - URMC

Neuroscience

Virus-Based Technique Could Enhance Maps of the Brain – Technology Networks

Virginia Tech scientists have improved upon a key method to map the zebrafish brain -- an advance that could improve understanding of how the human brain functions.

A wiring diagram of the brain would be a powerful tool to understand diseases of connectivity, said Yuchin Albert Pan, the Commonwealth Research Commercialization Fund Eminent Research Scholar in Developmental Neuroscience at theFralin Biomedical Research Institute at VTC. Autism spectrum disorder, for example, is characterized by a loss of long-distance connections and increase in local connections. Most neuropsychiatric disorders have connectivity aspects.

Although human brains are more complex, zebrafish brains share a common architecture as do all vertebrates. Determining the structure and function of cells called neurons and how they connect within the brain and between the brain and other structures such as the eye could provide clues to more precisely treat neurological diseases and eye injuries.

In a study in todaysFrontiers in Neuroanatomy, the scientists reported an improved, viral-based technique to trace brain connections between neurons in zebrafish using vesicular stomatitis virus (VSV), which labels cells as it spreads across the synaptic connections between neurons that are functionally wired together.

Until now, the use of viral vectors in zebrafish has been limited because the viruses, such as rabies or adeno-associated virus, often used by scientists to transfer molecules to cells in mammals, are not effective in fish.

To overcome this limitation,Virginia Tech scientiststried and validatedtheuseofVSV to trace connection patterns in neurons in zebrafish. The virus was engineered to label excitatory and inhibitory neurons that are connected via a nanoscopic structure called the synapse.

Before this study, the researchers had been successful with the approach, but the improved, second-generation version of the technique used a mutant version of VSV that was less toxic and longer-lived in the cells, making visualization of the connected neurons and the analysis of that connectivity possible up to five days after infection.

This is really exciting, because now we can not only record activity, but we also know something about the cell types involved, and how they connect, said co-lead author Manxiu Michelle Ma, a neurophysiologist and formerly a postdoctoral research associate in the Pan lab. The unique viral tracer benefits from reducedcytotoxicity, which enables the virus-infectedneurons to maintain their cellular integrity and express a fluorescentindicator to reveal neuronalactivity during visual stimulation. Furthermore, this technique can also define the neuron type,for example, if the neuron during a visual stimulus is an excitatory neuron or an inhibitory neuron.

Stanislav Kler, a virologist and co-lead author of the study who was also a postdoctoral research associate in the lab, said, The connectivity patterns between most neuronal types are mostly unknown. This gap in knowledge underscores the critical need for effective neural circuit mapping tools. This will get us a step closer to understanding how the brain stores and processes information and how we can manipulate these circuits for better health.

The research is especially significant for vision research.

To restore vision after diseases or injury that affect the eye itself including the cells in the eye that project to structures deep within the brain for subsequent processing of the visual world, the eye needs to connect to the right places in the brain, said Pan, who is a member of the Fralin Biomedical Research Institutes Center for Neurobiology Research. The small size and translucency of larval zebrafish are a unique experimental system to investigate whole brain neural circuits. Scientists working on vision regeneration can now look at whether there is functional connectivity.

Reference: Kler S, Ma M, Narayan S, Ahrens MB, Pan YA. Cre-Dependent Anterograde Transsynaptic Labeling and Functional Imaging in Zebrafish Using VSV With Reduced Cytotoxicity. Frontiers in Neuroanatomy. 2021;15:71. doi:10.3389/fnana.2021.758350

This article has been republished from materials provided by Virginia Tech. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Virus-Based Technique Could Enhance Maps of the Brain - Technology Networks

Neuroscience

$12.2 million to fund new Conte Center to study neurosteroids Washington University School of Medicine in St. Louis – Washington University School of…

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Complements efforts of Taylor Family Institute to develop treatments for psychiatric illness

Steven Mennerick, PhD, works in his laboratory, where he studies neurosteroids and their potential as antidepressants. The National Institute of Mental Health has awarded Washington University School of Medicine in St. Louis a $12.2 million grant to create a center aimed at advancing research into neurosteroids as treatments for depression and other psychiatric disorders.

The National Institute of Mental Health (NIMH) has awarded Washington University School of Medicine in St. Louis a five-year, $12.2 million grant to create a center aimed at advancing research into neurosteroids as treatments for depression and other psychiatric disorders.

The new Silvio O. Conte Center for Basic Neuroscience Research will be one of only 15 Conte Centers currently funded by the NIMH, of the National Institutes of Health (NIH). The centers research focus complements work performed at Washington Universitys Taylor Family Institute for Innovative Psychiatric Research, where scientists have focused since 2013 on the potential of neuroactive steroids to be used to treat psychiatric problems.

Psychiatric illnesses are a major cause of death and disability in the United States and around the world. Research by scientists at the Taylor Family Institute has added to the understanding of changes in the brain that underlie these disorders. Those researchers also have been involved in developing new treatments using neuroactive steroids.

In addition to tapping psychiatrists, neuroscientists, anesthesiologists and chemists at the School of Medicine, the new Conte Center also will involve researchers at Tufts University, Duke University and the University of Colorado. The overall goal is to identify pathways and receptors in the brain that interact with neuroactive steroids. The idea is that those proteins and receptors then might become treatment targets for new psychiatric drugs developed from neurosteroids.

This will be a discovery-based Conte Center, and we hope to leverage our catalogue of synthetic neurosteroids one of the largest in the world to find more effective treatments for depression and other psychiatric problems, said Steven Mennerick, PhD, co-director of the new center and the John P. Feighner Professor of Neuropsychopharmacology in the Department of Psychiatry at Washington University. Our center will unite and coordinate the efforts of internationally recognized investigators with expertise in the biology and chemistry of neurosteroids, as well as expertise in the treatment of psychiatric disorders.

The center is organized around three main projects. Alex S. Evers, MD, the Henry E. Mallinckrodt Professor of Anesthesiology, is the principal investigator of a project that aims to identify the cellular proteins targeted by neurosteroids and to characterize the structures of those binding sites.

The second project directed by Mennerick and Charles F. Zorumski, MD, the Samuel B. Guze Professor and head of the Department of Psychiatry will involve testing a prototype antidepressant neurosteroid to help determine what role various types of cellular receptors play as neurosteroids provide antidepressant effects in the brain.

The third project led by Jamie Maguire, PhD, a professor of neuroscience at Tufts University School of Medicine will test the compounds found most effective in the first two projects in animals that exhibit behaviors similar to what would be diagnosed as clinical depression in a person.

We believe there will be a synergy between our efforts to study and develop new treatments at the Taylor Family Institute and our work at the new Conte Center to identify the receptors and pathways through which neurosteroids exert their effect in the brain, said Zorumski, who is a co-director of the new center and director of the Taylor Family Institute. We want to learn which neurosteroids might be most effective as treatments and which receptors those compounds target.

One neuroactive steroid has had some early success treating depression. In 2019, the Food and Drug Administration approved brexanalone as a treatment for postpartum depression; however, the drug can cause significant sleepiness, and it must be delivered via intravenous infusions. The hope is that new treatments will have fewer side effects and be easier to use.

Our work at the Taylor Family Institute and the new Conte Center reflects the unique partnership weve developed in recent years between anesthesiology and psychiatry, Evers said. The drug ketamine is a perfect example. Its best known as an anesthetic, but we now know it also is useful as an antidepressant. Like ketamine, neurosteroids got their start as anesthetics.

Researchers at the Conte Center will have the opportunity to study the effects of hundreds of synthetic neurosteroids developed by Douglas Covey, PhD, the Andrew C. and Barbara B. Taylor Distinguished Professor of Psychiatry. A medicinal chemist, Covey has created a large catalogue of potential candidate compounds.

This work is supported by the National Institute of Mental Health of the National Institutes of Health (NIH). Grant number P50 MH122379

Washington University School of Medicines 1,700 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, consistently ranking among the top medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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$12.2 million to fund new Conte Center to study neurosteroids Washington University School of Medicine in St. Louis - Washington University School of...