Obama ja R. Douglas Fields napit vastakkain "aivoyhteyksien kartoittamisesta":
https://www.youtube.com/watch?v=C4cwjaOc6Lc
" R. Douglas Fields on Brain Mapping vs. Neuron Mapping
Neuroscientist R. Douglas Fields expresses concern that President Obama's BRAIN Initiative may be overlooking the primary cells that make up this complex organ. Fields encourages looking past the gray matter. Learn more about brain mapping and other views at WorldScienceFestival.com "
" Nature | Comment
Neuroscience: Map the other brain
R. Douglas Fields
04 September 2013
Glia, the non-neuronal cells that make up most of the brain,must not be left out of an ambitious US mapping initiative, says R. Douglas Fields.
The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative announced by US President Barack Obama in April seeks to map and monitor the function of neu- ral connections in the entire brains of experimental animals, and eventually in the human cerebral cortex.
Several researchers have raised doubts about the project, cautioning that mapping the brain is a much more complex endeavour than mapping the human genome, and its usefulness more uncertain.
I believe that exploring neural networks and developing techniques with which to do so are important goals that should be vigorously supported.
But simply scaling up current efforts to chart neural connections is unlikely to deliver the promised benefits - which include understanding perception, consciousness, how the brain produces memories, and the development of treatments for diseases such as epilepsy, depression and schizophrenia1.
A major stumbling block is the project's failure to consider that although the human brain contains roughly 100 billion neurons it contains billions more non-electrical brain cells called glia.
These reside outside the neuronal 'connectome' and operate beyond the reach of tools designed to probe electrical signalling in neurons.
Dismissed as connective tissue when they were first described in the mid-1800s, glia have long been neglected in the quest to understand neuronal signalling.
Research is revealing that glia can sense neuronal activity and control it.
Various studies also indicate that glia operate in diverse mental processes, for instance, in the formation of memories. They have a central role in brain injury and disease,and they are even at the root of various disorders - such as schizophrenia and Alzheimer's - previously presumed to be exclusively neuronal. That the word 'glia' was not uttered in any of the announcements of the BRAIN Initiative, nor written anywhere in the 'white papers' published in 2012 and 2013 in prominent journals outlining the ambitious plan, speaks volumes about the need for the community of neuroscientists behind the initiative to expand its thinking.
All major glial cell types in the brain - oligodendrocytes, microglia and astrocytes - communicate with each other and with neurons by using chemical neurotransmitters and gap junctions, channels that permit the direct transfer between cells of ions and small molecules (see ‘Roles of glial cells’).
Roles of glial cells
R. DOUGLAS FIELDS
Oligodendrocytes (green)
Form myelin electrical insulation, increasing conduction velocity by at least 50 times.
Provide vital metabolic support for axons (purple). Involved in multiple sclerosis, amyotrophic lateral sclerosis and the inhibition of repair after spinal-cord injury.
Astrocytes (red and green)
Ensheath synapses, regulate neuronal excitability and synaptic transmission. Res- pond to injury by secreting extracellular matrix proteins. Implicated in neurogenesis, cell migration, and many neurological and psychiatric disorders.
Microglia (green)
Highly motile and responsive to nervous-system injury and infection. Monitor electri-cal activity in neurons and prune synaptic connections (red). Involved in almost all nervous-system diseases and in certain psychiatric conditions.
More
Oligodendrocytes produce the myelin sheath, the insulating material that surrounds nerve fibres called axons. This sheath greatly increases the speed at which electrical signals are transmitted through axons - a crucial feature because nervous-system function depends on information being transmitted at high speed.
Biologists have known for decades that microglia - the immune cells of the brain - respond to infection and brain trauma by clearing away diseased or damaged tissue and releasing substances that stimulate repair. But last year, a study 5 of how eye-brain connectivity is established in developing mice showed that microglia also prune back synapses and rewire neural connections in a healthy brain, depending on the individual's visual experience shortly after birth.
Various studies 3 have revealed that astrocytes regulate the transmission of electri-cal signals across synapses by modifying the concent-ration of extracellular potas-sium;controlling local blood flow;releasing and taking up neurotransmitters and other neuromodulatory substaces;delivering nutrients to neurons;and altering the geomet-ry and volume of space between brain cells. All of these things influence nervous-system communication and plasticity.
Glia in action
This video captures the waves of calcium ions passing between rat astrocytes as they engage in non-electrical communication.
When experts on neuronal plasticity and computational neuro-science came toge-ther with glial experts at a workshop in February entitled Glial Biology in Learning and Cognition 6, held at the US Na- tional Science Foundation in Arlington, Virginia, our unanimous conclusion was that neurons working alone provide only a partial ex-planation for complex cognitive processes, such as the formation of memories. The complex branching structure of glial cells and their relatively slow chemical (as op-posed to electrical) signalling in fact make them better suited than neurons to certain cognitive processes.These include processes requiring the integration of information from spatially distinct parts of the brain, such as learning or the experiencing of emo-tions, which take place over hours, days and weeks, not in milliseconds or seconds.
Pioneering research on glia is even offering glimpses into the mechanisms that un-derlie learning, other forms of plasticity and information processing.For instance, my research group has established that,in vitro,the impulse traffic in an axon can control its myelination by glia 7. Because myelination determines the speed at which an electrical signal is transmitted through an axon, it can influence how many inputs fire on to a neuron at the same time - a process that is fundamental to most learning and synaptic plasticity. When people acquire new skills,from juggling to playing computer games, the structure of specific myelinated regions of their brains changes 8.
We are only beginning to learn about the diversity, connectivity and function of astro-cyte networks. Various studies suggest that astrocytes have anatomical and physio-logical properties that may impose higher-order organization on information proces-sing in the brain. In the grey matter of the cerebral cortex and hippocampus, astro-cytes are organized in non-overlapping domains. The significance of this tile-like organization is unknown,but one human astrocyte (an intricate, bush-like cell) can encompass, and therefore influence,two million synapses 9.In fact,human astrocytes are markedly dif- ferent from those of other animals. Mice that have had a proportion of their astrocytes replaced with human ones show increased synaptic plasticity and faster learning 9 in a range of tests.
Neuroscientists have known for several decades that glia cause certain diseases. Nearly all cancers originating in the brain derive from glia (which, unlike mature neu- rons, undergo cell division). In multiple sclerosis, the myelin sheaths around axons become damaged, and in HIV-associated neurological conditions, the virus infects astrocytes and microglia, not neurons. Many neurological disorders that were once considered to be exclusively neuronal in nature are now also known to involve glia, including Rett syndrome,a neurodevelopmental condition that includes autism-like symptoms, the motor-neuron disease amyotrophic lateral sclerosis, Alzheimer's di-sease and chronic pain. The same is true for various other develop-mental and psy- chiatric conditions such as schizophrenia, depression and obsessive – compulsive disorder 2, 3.
Agenda for success
Mapping and monitoring the entire human cerebral cortex is expected to require an investment comparable to that needed for the Human Genome Project: US$ 3.8 billion 1. The public will not support such a major expenditure of public funds for a scientific research project if the promised benefits are oversold,if they do not under-stand the benefits or if the costs are not realistic. This was demonstrated in 1993 by the US Congress's cancellation of a multibillion-dollar project to build a supercon-ducting super collider, the construction of which was already under way in Waxahachie, Texas.
Unlike the quest to capture the Higgs boson or to land a human on the Moon, few people question the need to understand the human brain. The brain is the greatest enduring mystery of the human body,and intellectual disability, brain cancer, spinal- cord injury, senile dementia and mental illnesses such as schizophrenia and dep-ression touch the lives of almost everyone. But on its current trajectory, the BRAIN Initiative risks failure - both scientifically and in terms of public support.
At the World Science Festival in New York in June, one participant argued that infor-mation about glia will be a by-product of neuronal mapping and of the development of technologies to trace and record neuronal connections. This is implausible. New methods to monitor electrical signalling in neurons, such as voltage-sensitive dyes or nanoparticles that sense the electrical potential across membranes, will be of little use for understanding cells that do not communicate using electrical impulses. It is this view that has perpetuated our comparative ignorance about glia.
Moreover,the exclusion of glia from the BRAIN Initiative underscores a more general problem with the project:the assumption that enough measuring of enough neurons will in itself uncover 'emergent' properties and, ultimately, cures for diseases 1,4. Ra-ther than simply materializing from measurements of “every spike from every neu- ron” 1,4,better understanding and new treatments will require hypothesis-directed re-search. The 302 neurons and 7,000 connections that make up the nervous system of the roundworm Caenorhabditis elegans were mapped in the 1970s and 80s. More than two decades later, little is understood about how the worm's nervous system produces complex behaviours.
In any major mapping expedition, the first priority should be to survey the uncharted regions.Our understanding of one half of the brain (the part comprised of astrocytes, oligodendrocytes and microglia) lags a century behind our knowledge of neurons. I believe that answers to questions about the brain and public support for a large-scale study are more likely to come from expanding the search into this unknown territory. As a first step,tools such as optogenetic methods and mathematical models are needed to assess the number,distribution and properties of different kinds of glial cell in different brain regions, and to identify how glia communicate with each other and with neurons, and what developmental and physiological factors affect this. This exploration into the ´other brain´ must be done together with the proposed studies of neurons. It cannot be achieved as a by-product of them. "
Related stories
Neuroscience: Solving the brain
The benefits of brain mapping
Whole human brain mapped in 3D
Hankken wikisivut antavat kuvan hölmöstä mammuttihankkeesta:
The BRAIN Initiative
(Brain Research through Advancing Innovative Neurotechnologies, also referred to as the Brain Activity Map Project) is a proposed collaborative research initiative announced by the Obama administration on April 2,2013,with the goal of mapping the activity of every neuron in the human brain.[2][3][4][5][6] Based upon the Human Genome Project, the initiative has been projected to cost more than $300 million per year for ten years. [2] NIH Director Dr. Francis Collins and President Barack Obama announcing the BRAIN Initiative
Announcement
In September 2011, molecular biologist Miyoung Chun of The Kavli Foundation organized a conference in London,at which scientists first put forth the idea of such a project.[4][7] At subsequent meetings, scientists from US government laboratories, including members of the Office of Science and Technology Policy, and from the Howard Hughes Medical Institute and the Allen Institute for Brain Science,along with representatives from Google, Microsoft, and Qualcomm, worked on further plans for the project. [2]
In a news conference on April 2,2013, President Obama announced that he would seek an initial expenditure of $100million for fiscal year 2014. [4][5][6] House Majority Leader Eric Cantor said that he would be likely to support the expenditure. [5] Addi-tional support will be provided by the Allen Institute for Brain Science, the Howard Hughes Medical Institute, the Kavli Foundation, and the Salk Institute for Biological Studies. [6] The White House announced that a detailed plan would be formulated by the end of the summer by a working group from the National Insti-tutes of Health, the Defense Advanced Research Projects Agency (DARPA), and the National Science Foundation, led by neuroscientists Cornelia Bargmann and William Newsome. [4][5][6]
Experimental approaches
News reports about the initiative indicated that it would seek to map the activity of each of the approximately 100 billion neurons in the human brain, [2] although initial studies will be performed in mice and other animals. [3]
In a 2012 scientific commentary outlining experimental plans for a more limited pro-ject, Alivisatos et al.outlined a variety of specific experimental techniques that might be used to achieve what they termed a "functional connectome",as well as new tech-nologies that will have to be developed in the course of the project. [1] They indicated that initial studies might be done in Caenorhabditis elegans, followed by Drosophila, because of their comparatively simple neural circuits.Mid-term studies could be done in zebrafish, mice, and the Etruscan shrew, with studies ultimately to be done in pri- mates and humans. They proposed the development of nanoparticles that could be used as voltage sensors that would detect individual action potentials as well as na- noprobes that could serve as electrophysiological multi-electrode arrays.In particular, they called for the use of wireless, non-invasive methods of neuronal activity detec-tion, either utilizing micro-electronic very-large-scale integration,or based on synthe- tic biology rather than micro-electronics.In one such proposed method, enzymatically produced DNA would serve as a "ticker tape record" of neuronal activity, [1][8] based on calcium ion-in-duced errors in coding by DNA polymerase. [9] Data would be ana-lyzed and mo-deled by large scale computation. [1] A related technique proposed the use of high-through-put DNA sequencing for rapidly mapping neural connectivity. [10]
Working group
The advisory committee is:[11]
- Cornelia Bargmann, PhD (co‐chair), The Rockefeller University
- William Newsome, PhD (co‐chair), Stanford University
- David J. Anderson, PhD, California Institute of Technology
- Emery Brown, MD, PhD, Massachusetts Institute of Technology
- Karl Deisseroth, MD, PhD, Stanford University
- John Donoghue, PhD, Brown University
- Peter MacLeish, PhD, Morehouse School of Medicine
- Eve Marder, PhD, Brandeis University
- Richard Normann, PhD, University of Utah
- Joshua Sanes, PhD, Harvard University
- Mark Schnitzer, PhD, Stanford University
- Terry Sejnowski, PhD, Salk Institute for Biological Studies
- David Tank, PhD, Princeton University
- Roger Y. Tsien, PhD, University of California, San Diego
- Kamil Ugurbil, PhD, University of Minnesota
Reactions
Scientists offered differing views of the plan. Neuroscientist John Donoghue said that the project would fill a gap in neuroscience research between, on the one hand, acti-vity measurements at the level of brain regions using methods such as fMRI, and, on the other hand,measurements at the level of single cells. [3] Psychologist Ed Vul ex-pressed concern, however, that the initiative would divert funding from individual in-vestigator studies. [3] Neuroscientist Donald Stein expressed concern that it would be a mistake to begin by spending money on technological methods, before knowing exactly what would be measured. [4] Physicist Michael Roukes argued instead that methods in nanotechnology are becoming sufficiently mature to make the time right for a brain activity map.[4]
In a January 2013 meeting, a group of neuroscientists concluded that the project would generate about 300 exabytes of data every year, presenting a significant tech-nical barrier. [12] Furthermore, the usefulness of most of the currently available high-resolution brain activity monitors is limited because they are highly invasive, being implanted by a process that involves surgically opening the skull. [12] "
Projektin johtaja löytyy täältä: sama henkilö joka on kartoittanut sukkulamadon kaikkien 123 neuronin kaikki (?) 7000 (keskinäistä?) kytkentää, ja kuienkin niin, että Fieldsin mukaan elukan käyttätymisestä ei tiedetä nyt sen enempää kuin toita toineta ennekään.
Obama to Unveil Initiative to Map the Human Brain
By JOHN MARKOFF and JAMES GORMAN
Published: April 2, 2013
President Obama on Tuesday will announce a broad new research initiative, starting with $100 million in 2014,to invent and refine new technologies to understand the human brain, senior administration officials said Monday.
Fred R. Conrad/The New York Times
Cori Bargmann of Rockefeller University will help lead a study of the brain in action.
Related
-
Obama Seeking to Boost Study of Human Brain (February 18, 2013)
-
Times Topic: Brain
A senior administration scientist compared the new initiative to the Human Genome Project, in that it is directed at a problem that has seemed insoluble up to now: the recording and mapping of brain circuits in action in an effort to “show how millions of brain cells interact.”
It is different, however, in that it has, as yet, no clearly defined goals or endpoint. Coming up with those goals will be up to the scientists involved and may take more than year.
The effort will require the development of new tools not yet available to neuroscien-tists and, eventually, perhaps lead to progress in treating diseases like Alzheimer’s and epilepsy and traumatic brain injury. It will involve both government agencies and private institutions.
The initiative, which scientists involved in promoting the idea have been calling the Brain Activity Map project,will officially be known as Brain Research Through Advan- cing Innovative Neurotechnologies, or Brain for short;it has been designated a grand challenge of the 21st century by the Obama administration.
Three government agencies will be involved:the National Institutes of Health, the De-fense Advanced Research Projects Agency and the National Science Foundation. A working group at the N.I.H., described by the officials as a “dream team,” and led by Cori Bargmann of Rockefeller University and William Newsome of Stanford Univer-sity, will be charged with coming up with a plan, a time frame, specific goals and cost estimates for future budgets.
The initiative exists as part of a vast landscape of neuroscience research supported by billions of dollars in federal money. But Dr. Newsome said that he thought a small amount of money applied in the right way could nudge neuroscience in a new direction.
“The goal here is a whole new playing field, whole new ways of thinking,” he said. “We are really out to catalyze a paradigm shift.”
Brain researchers can now insert wires in the brain of animals, or sometimes human beings,to record the electrical activity of brain cells called neurons,as they communi- cate with each other. But, Dr. Newsome said, they can record at most hundreds at a time.
New technology would need to be developed to record thousands or hundreds of thousands of neurons at once.And,Dr. Newsome said, new theoretical approaches, new mathematics and new computer science are all needed to deal with the amount of data that will be garnered.
As part of the initiative, the president will require a study of the ethical implications of these sorts of advances in neuroscience.
While news of the announcement has been greeted with enthusiasm by many researchers in fields as diverse as neuroscience, nanotechnology and computer science, there are skeptics.
“The underlying assumptions about ‘mapping the entire brain’ are very controversial" , said Donald Stein,a neuroscientist at Emory University in Atlanta. He said changes in brain chemistry were “not likely to be able to be imaged by the current technologies that these people are proposing.” "
Winner’s story: Donald G. Stein
Brain Injury's Stonnington Prize for Best Review Paper 2015 "
Vuoden 2015 parhaaksi aivovauriolääkäriksi USA:ssa valittu tri Donald Stein pitää "aivogeenikonnektomia" hölynpölyideana.
"Emphasizing the development of technologies first, he said, is not a good approach. “I think the monies could be better spent by first figuring out what needs to be mea-sured and then figuring out the most appropriate means to measure them.” he said. “In my mind, the technology ought to follow the concepts rather than the other way around.”
However,supporters of the initiative argued that it could have a similar impact as the Sputnik satellite had in the 1950s, when the United States started a significant nationwide effort to invest in science and technology.
“This is a different time,” said Michael Roukes, a physicist at the California Institute of Technology. “It makes sense to have a brain activity map now because the maturation of an array of nanotechnologies can be brought to bear on the problem.”
Michael Roukes at TEDxCaltech, 1/14/11
While the dollar amount committed by the Obama administration does not match the level of spending on the Human Genome Project, scientists said that whatever was spent on the brain initiative would have a significant multiplier effect. The Salk Insti-tute in La Jolla, Calif., is contributing money, said Terrence J. Sejnowski, head of the institute’s computational biology laboratory,adding that the project would have an impact at the neighboring University of California, San Diego, campus.
“One concrete example is that the chancellor has gotten excited about this and has decided that it is a great thing to invest in,” Dr. Sejnowski said. “That means hiring new faculty and creating new space.”
Idea ja siis mös "tarve" lähtivät tieteen ulkopuolelta...
The project grew out of an interdisciplinary meeting of neuroscientists and na-noscientists in London in September 2011. Miyoung Chun, a molecular biologist who is vice president of scientific programs at the Kavli Foundation, had organized the conference. Her foundation, she said,supports the idea that the next big scientific discoveries will come from interdisciplinary research.
Dr. Miyoung Chun was invited to meet President Obama three times to discuss her work on the brain.
“Federal funding is scarce these days,and I realized we need inspiring projects that can awake everyone’s imagination,” she said. “It occurred to me that this is a very inspiring idea.”
This article has been revised to reflect the following correction:
Correction: April 4, 2013
An article on Tuesday about a research initiative to invent and refine technologies to understand the human brain misstated the relationship between the Salk Institute and the University of California, San Diego. The Salk Institute, which is giving money to the research initiative, is an independent institute; it is not based at, or part of, the university.
A version of this article appeared in print on April 2, 2013, on page A12 of the New York edition with the headline: Obama to Unveil Initiative To Map the Human Brain.
Levi-Montalcinin valintaperiaate päässyt "unohtumaan"!!!
Tai sitten kyseessä on harkittu hölynpölytiedehyökkäys nimenomaan sitä vastaan.
Muun ohella näyttää päässeen kokonaan unohtumaan sodanjälkeisen ajan neurofy-siologian yksi kulmakivi v.1986 lääketiteen nobelistin Rita Levi-Montacinin valinta-periaate, joka sanoo,että geenit eivät määrää aksniyhteyksiä ainakaan ykstyiskohtai- sesti vaan neuroneja ja niiden yhteyksiä tuotetaan "yli tarpeen" ja näistä valikoituvat toimivien neuroyhteyksien pohjaksi ne jotka yhdistyvät kudokseen siten, että saavat siitä kavutekijää (BNF):
Sodanjälkeisen ajneurofysiologian yksi keskeinen kulmakivi on ollut ja on edelleen vuoden 1986 lääketieteen nobelsitin Rita Levi-Montalcinin valintaperiaate, joka tar- koittaa, että perimä ei määrää hermosolujen konkreettista yhteyksiä, vaan neuroneja ja niiden haarakkeita tuotetaan yli tarpeen ja näistä jäävät henkiin ne, jotka löytävät oikeaan kohteseen. Helsingin yliopiston Eero Castren kirjoittaa (Tieteessä tapahtuu 4/2004):
” Ääreishermoston hermosoluja siis tuotetaan ylimäärin ja niitä kuolee kehityksen ai-kana sitä enemmän,mitä vähemmän hermotettavaa kudosta on. Hermotettava kudos ei siten stimuloikaan hermosolujen jakautumista, vaan pitää kohdekudoksen saavut-taneita hermosoluja hengissä.Tällä mekanismilla kehittyvä organismi voi varmistaa kohdekudoksen optimaalisen hermotuksen mahdollisimman vähäisen hermosolu-määrän avulla.Levi-Montalcini havaitsi,että hermosolujen kohdesolut tuottivat tekijää, joka oli välttämätön ääreishermoston solujen hengissä säilymiselle ja jonka riittäväs-tä saatavuudesta hermosolut kilpailevat.Kehityksen aikana hengissä siis säilyivät vain ne hermosolut, jotka muodostivat toimivan yhteyden kohdesolun kanssa ja kykenivät siten saamaan riittävästi sen erittämää kasvutekijää (NGF). "
Nobelisti, kansanedustaja (Italian yhdisynyt työväenpuolue), Rita Levi-Montalcini vuonna 2009
Levi-Montalcini löysi tämän periaatteen tutkiessaan kanan alkioiden hermoston kehi-tystä II maailmansodan aikana kotilaboratoriossaan Italiassa, juutalaisena tieteellistä viroista syrjäytettynä. Seuraavaksi hän ryhtyi etsimään tuota kasvutekijää NGF:ää (neuro growth factor), jonka löytämisestä (1968) hän sai lääketieteen Nobelin palkin-non (1986) yhdessä Stanley Cohenin (USA) kanssa. Hän toimi Italiassa Rooman ja USA:ssa Missourin St.Louisin yliopistoissa. Keskushermostossa prosessi on vielä huomattavasti monivaiheisempi,ja syntyy paljon yhteyksiä, joiden signaalinjohtavuus vaihtelee suuresti glia-solujen vaikutuksiin liittyen (Fieldsin mekanismi).
http://hameemmias.vuodatus.net/lue/2015/09/tieteellinen-vallankumous-neurofysiologiassa
http://www.nature.com/news/surprising-contenders-emerge-for-trump-s-nih-chief-1.21295
" Nature | Breaking News
Surprising contenders emerge for Trump's NIH chief
Reproducibility guru, former defence-research official and controversial entrepreneur rumoured to be on list, along with current NIH leader and a congressman.
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Patrick Soon-Shiong, Francis Collins, Andy Harris and John Ioannidis are rumoured to be under consideration.
Could US president-elect Donald Trump be close to choosing a leader for the National Institutes of Health (NIH)?
Current NIH chief Francis Collins and Representative Andy Harris (Republican, Maryland), both front-runners for job, met separately with Trump on 11 January, as did billionaire surgeon Patrick Soon-Shiong on 10 January. Several people familiar with the Collins and Harris meetings described them as job interviews.
Other rumoured candidates include Geoffrey Ling, a retired Army neurosurgeon and former director of biotechnology at the Defense Advanced Research Projects Admi- nistration (DARPA), and John Ioannidis, an epidemiologist at Stanford University in California who has pushed for reproducibility in biomedical science.
Although Ioannidis says that he has not been approached by Trump’s staff, sources close to the transition team say that the scientist has been floated for the NIH posi-tion. “If they call, my first priority would be to make sure there are no strings attached in promoting any anti-science ideas", Ioannidis says, such as linking vaccines to autism.
But Collins - who has led the NIH since August 2009 - has already said that he would continue on if Trump asked. That would make Collins, the longest-tenured member of President Barack Obama’s science “dream team”, the first NIH director since the 1970s to be chosen by two presidents.
Known for his skill at communicating with lawmakers, Collins has the backing of four senior Republican members of Congress who signed a 2 December letter urging Trump to keep him on. But extending a single director’s tenure for so long may not be in the agency’s best interest, says Ezekiel Emanuel, a bioethicist at the University of Pennsylvania in Philadelphia.
“In general, I think more than eight years has not been a good idea", he says. “There’s a cycle, and eight years is hard to have new ideas and new energy.”
Others worry that Trump could go too far in the opposite direction,and pick an NIH chief without a significant science track record or experience managing large re-search projects. With both Harris and Soon-Shiong, ”my concern would be that this is a person who hasn't really been tested”, says Keith Yamamoto,a biologist at the University of California, San Francisco.
Culture clash?
Harris, an anaesthesiologist,has taken a strong interest in the NIH during his three terms in the House of Representatives.He helped write the 21st Century Cures Act,a law enacted last year to reform research and development at the NIH and the Food and Drug Administration, and pushed the NIH to develop a five-year strategic plan.
And Harris has taken a special interest in early-career scientists,proposing legisla-tion that would force the NIH to set aside more money for young researchers and to lower the age at which investigators receive their first grant.
Many lobbyists and science advocates contacted by Nature refused to comment on the record about Harris. Some expressed worry that his policy positions - including staunch opposition to research with human embryonic stem cells - would be at odds with the NIH’s culture.
“He would be much more entrepreneurial in outlook and attitude” than Collins, says one longtime NIH-watcher who works in science policy. “If it's Harris, I think there would be a mass exodus of senior leaders.”
Still, Harris may benefit from having served in the House with Representative Tom Price, the Georgia Republican who Trump has tapped to lead the Department of Health and Human Services, which oversees the NIH.
And his interest in early-career scientists could give him an edge with key Trump ad-visers: Silicon Valley billionaire Peter Thiel, who met with Trump on 11 January, and former House speaker Newt Gingrich. Both are said to be particularly interested in improving conditions for young researchers.
Another candidate who may appeal to Thiel is Ling. As the first director of DARPA's biotechnology office,Ling oversaw the kind of 'high-risk,high-reward' projects that the NIH does not often fund - and Thiel has said that science needs more bold, entre-preneurial ventures. But there is no indication that Ling has met with Trump as some of the other rumoured candidates have done, and he has not responded to Nature's request for comment.
Dark horse
If Trump is looking for an outsider candidate, that could boost the chances of Soon-Shiong, a billionaire surgeon who runs a network of health companies called NantWorks.
Soon-Shiong was among the scientists who advised Vice President Joe Biden’s Cancer Moonshot initiative. He also runs his own, separate programme called Cancer MoonShot 2020, a collaboration between several pharmaceutical companies developing immunotherapies.
Sources who have spoken with the transition team say that Soon-Shiong is also under consideration for other government positions, including presidential science adviser. (Another rumoured candidate for science adviser, former NIH director Elias Zerhouni, told Bloomberg News on 9 January that he did not want to leave his current post at drug giant Sanofi.)
- Nature
- doi:10.1038/nature.2017.21295
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USA:n ja Kuuban johtavat neurotietelijät keskustelevat yhteistyöstä
USA:n ja Kuuban johtavat neurotietelijät R. Douglas Fields ja Mitchell Valdés-Sosa keskustelevat näköaloista ja tieteellisestä yhteistyöstä.
Five Questions for Mitchell Valdés-Sosa
A neuroscientist discusses how academia and scientific research operate in communist Cuba, and the need for funding from foreign nations.
Mitchell Valdés-Sosa is the chief executive and co-founder of the Cuban Neuroscience Center (CNEURO), established in 1991.
Visual by R. Douglas Fields
.
It is helpful to appreciate some of the ways that higher education and research ope-rate differently in communist Cuba. In contrast to the local institutional and individual control of decisions in the U.S., the central government in Cuba makes career and educational decisions for its citizens. Scientific research is directed by authorities to meet the needs of the developing country, and Ph.D. dissertation proposals must sa-tisfy this goal for approval. Much of the graduate education takes place in biotechno-logy companies and research centers that are authorized by the government - a situ-ation resembling internships in the U.S. Development, production, and marketing of products from biomedical research and education are all carried out in the same center, and the sales of these products provide financial support to the institution.
With the breakup of the Soviet Union in 1991,Russian economic support of Cuba en- ded, sending the country into a calamitous economic tailspin called the “Special Pe-riod” Scarcity of resources, crumbling infrastructure, lack of transportation and hou-sing,food rationing and famine gripped the country.Venezuela then became a strong economic supporter until it suffered its own economic crash with the collapse of the oil market.Now,with the Obama administration’s reset of U.S.-Cuban relations, Cuba is looking to the West for a better future - though the incoming U.S. president Donald Trump brings uncertainty.
Valdés-Sosa is the chief executive and co-founder of the Cuban Neuroscience Cen-ter (CNEURO),which was established in 1991.He is responsible for the center’s daily operations and the development of new products. He received his medical degree from the University of Havana in 1972, and his Ph.D. from the National Research Center of Cuba in 1979 for his work on the physiology of the human auditory system. In addition to serving as the director of CNEURO, Valdés-Sosa is head of the Natio-nal Group for Clinical Neurophysiology for the Cuban Ministry of Public Health, and a member of both the Cuban Academy of Sciences and the Cuban Society for Neuro-science. In 2006, he was appointed as an honorary professor at the University of Illinois at Chicago.
The interview was conducted last month, and our conversation has been edited for clarity.
Undark — How does one become a neuroscientist in Cuba?
Valdés-Sosa - The students that we recruit have usually done their undergraduate thesis research with us or with other neuroscience centers in Cuba. We have people coming in from medicine,computer science, physics, mathematics,biology, psycholo-gy, software engineering, biomedical science, and electrical engineering. There are neuroscience classes for undergraduate students in psychology and biology, but for all the rest, students become involved in neuroscience by working with us.
Other students are recruited because the Ministry of Labor finds a job for every person who graduates, and they begin to work with us in what is called their “social service.” All graduates from Cuban universities receive their education free,but when they graduate they have to perform two to three years of compulsory social service, and most continue for a year or two more.
UD — Students are selected for admittance to the master’s and Ph.D. programs by a central committee for all of Cuba; How does that process work?
VS — Students are selected by the committee according to their grades and the opi- nion of their classmates.It is a public thing,discussed by the classmates openly in the university. It could be seen as a conflict of interest to have students influencing the decision, but it is a situation where people are discussing publicly the merits of who works harder.
The Cuban Neuroscience Center is the coordinator of the master’s degree program in Cuba for neuroscience, but other institutes participate. Then after completing the master’s degree program, some individuals are selected to go on to the Ph.D. prog-ram. We are also the coordinators of the Ph.D.program. In fact,we are also the coor-dinators of the clinical neurophysiology program. So the basic science part of the cli-nical neurophysiology training for medical doctors is here, but then they go to the big teaching hospitals in Havana.
UD — How is the Ph.D. program structured and funded?
VS — Fidel Castro proposed creating what he called “closed cycle centers”.The cen- ters would do basic research,applied research, development, have their own produc- tion facilities, and have their own companies, from which the income goes back to support the research. Our center was part of that effort. Our conception is that the use of technology has to be a pyramid. We try to develop tools that are for massive use that are very low cost.
UD — What was the process when you received your education?
VS — Now my case was very different.I was recruited in 1972.I was born in Chicago and came to live in Cuba in 1961 when I was 11 years old. My father was a Cuban doctor living in the U.S. and he had participated in the revolutionary movement, the 26th of July movement. He returned to Cuba to help develop medicine here and be-came a professor at the University of Havana.You must remember that in 1959,Cuba had 6,000 doctors. Immediately after the revolution, 3,000 left for the U.S. My father was one of the few coming the other direction.
Fidel Castro said at the time that we have to develop biomedical research in Cuba. I and others responded to this personal call by Fidel in the same way that people left their schools and went into the countryside to teach people to read and write. I was part of the initial group of people who joined this effort and we became the foundation for all Cuban biomedical technology.
The first Ph.D. thesis in Cuba was defended in 1972 by Dr. Thalia Harmony, and she was my professor. After Dr. Harmony left Cuba for Mexico,her successor had a heart attack, and I was then named in his place as head of the Department of Neurophy-siology at the National Research Center in Havana. The Cuban Neuro-science Center began in 1991 and I was appointed director. My twin brother, Pedro, is vice director for research at the Cuban Neuroscience Center.
UD — What challenges must be overcome to develop neuroscience in Cuba, and what effect do you think the election of Trump will have?
VS — We have one serious problem, which is funding. The government gives us generous support in Cuban pesos, but there is very little hard currency, which we need to buy equipment or to travel abroad. Some of our centers that have successful “closed cycle” products can re-channel some of the money from international sales, but when you start analyzing research and education as a business, you start putting more money on the low risk projects. So what we need first is access to funding agencies across the world. Hopefully, we can receive funding from the U.S.
Second, we would like more infusions into Cuba of venture capital from private investors and U.S. companies.
We are also working to establish joint Ph.D.programs and master’s degree programs with other countries, but we are a small country. If everybody goes abroad to study for three years, science here is finished. The brain drain is an issue. It is happening, but it is happening all over the world. People tend to study abroad for a number of years, and sometimes they stay abroad. It has become a bigger problem in the last few years.
Salaries, we think, will have to grow, especially because of competition from the gro-wing private sector.Employees of the State now have lower salaries than people who have their private restaurants or whatever. This is a problem that has to be solved.
If Cuban and American politics stay the same or degrade under the new administra-tion in the U.S., we would do what we have done up to now. We would concentrate on Europe, Canada, Japan, and now China — which has emerged as a major player in science — as well as South America.
So let’s see what happens. I mean everybody is worried.
R. Douglas Fields is a neuroscientist. His last article for Undark, “Blind Rage and the Killing at Carderock,” appeared in November, 2016.
YLEn puutaheinää intuitiosta:
https://areena.yle.fi/1-3257820
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http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC4426493&blobtype=pdf
Glial Regulation of the Neuronal Connectome through Local and Long-Distant Communication
R. Douglas Fields1,*, Dong Ho Woo1, and Peter J. Basser21 Nervous System Development and Plasticity Section, The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Figure 2. Astrocytes Are Intimately Associated with Tens of Thousands of Synapses through Highly Ramified Slender Branches Astrocytes can influence neuronal con-nectivity by binding multiple synapses and multiple neurons into functional assemb-lies,but astrocytes also operate at a subcellular level to sense and modulate synaptic activity at single synapses.
(A) A single astrocyte from the neocortex of an adult mouse; note the cell body, multiple branches, and intricate fine highly branched terminals.
(B) An enlargement and surface rendering of the astrocyte processes shown in (A). Courtesy of Eric Bushong and Mark Ellisman at the National Center for Microscopy and Imaging Research (University of California, San Diego). See Shigetomi et al. (2013) for additional information. The large tick marks are 5 mm in (A) and 0.5 mm in (B).
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Map the Brain – Not Just Neurons
In any major mapping expedition, shouldn’t the first priority be to survey the unchar-ted regions? In mapping the brain, that would be charting the neglected half of the brain – glia.
The Brain Mapping Initiative announced by President Barack Obama earlier this year seeks to map and monitor the function of neural connections in the entire brain of ex-perimental animals, and eventually in the human cerebral cortex.Several researchers have raised doubts about the project, cautioning that mapping the brain is a far more complex endeavor than mapping the human genome, and its usefulness more uncertain.
I believe that exploring neural networks and developing new techniques to do so are important goals that should be supported vigorously. But simply scaling up current efforts to chart neural connections is unlikely to deliver the promised benefits: an un-derstanding of how the brain produces perception, memories and consciousness, or treatments for diseases such as epilepsy, depression and schizophrenia.
A major stumbling block is the project’s failure to consider that while the human brain contains approximately 100 billion neurons, it contains billions more non-electric brain cells called glia.These reside outside the neuronal ‘connectome’ and operate beyond the reach of tools designed to probe electrical signaling in neurons.
Dismissed as connective tissuewhen they were first described in the mid-1800s, glia have long been neglected in the quest to understand electrical signaling in neurons.
Recent research is revealing that glia can sense neuronal activity and control it. Glia operate in diverse mental processes, for instance, in the formation of memories; are central in brain injury and disease; and even the root of various disorders, such as schizophrenia and Alzheimer’s, previously presumed to be exclusively neuronal.
Our understanding of one half of the brain (the part comprised of astrocytes, oligo-dendrocytes and microglia) lags a century behind our knowledge of neurons. I be-lieve that answers to questions about the brain and public support for a large-scale study are more likely to come from expanding the search into this unknown territory.
To read the full article in this week’s Nature, please see:
http://www.nature.com/news/neuroscience-map-the-other-brain-1.13654
For additional information from the World Science Festival on this topic see this ar-ticle on the Brain Mapping Salon Held at the WSF.It featured many of the architects of the proposal in a panel discussion of its scope and objectives:
For some videos of the event see: http://worldsciencefestival.com/
This article first appeared on BrainFacts.org
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3 Comments
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Thank you. Yes, the Nature Comment seems to have had an impact. There is not much detail about glial research in the interim report, but this is good news to see glia recognized! We are seeing science in action–this is still a work in progress. Let’s hope we engage the public in supporting research on the brain; the source of so many difficult neurological and psychological problems–two and a half pounds of flesh that can think!
Douglas, congratulations on the clear results your Nature article had on the September 16 NIH Interim Report (link below). This is very good news for all of us following glial research.
http://www.nih.gov/science/brain/09162013-Interim%20Report_Final%20Composite.pdf
Advisory Committee to the NIH Director INTERIM REPORTI count 21 occurrences of the term glia in the report(!) This compares to ZERO references in the previous publications of the BRAIN Initiative committee — as Douglas pointed out in Nature. Bravo, sir.
If you have any comments on NIH’s response,I’d like to hear it. I suppose it is possible they are just giving lip service to quiet the chorus of critics that were aroused by your Nature article. But the response seems genuine to me, and hopefully will result in some decent portion of funding going to glial work.
Here’s another review on the Interim Report,
http://www.newyorker.com/online/blogs/elements/2013/09/mapping-the-future-of-neuroscience.html
A Map for the Future of Neuroscience— William Croft
on September 21, 2013 at 2:30 pm
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Here’s a recent news report on the reaction to the Nature Comment.
http://www.biosciencetechnology.com/articles/2013/09/top-neurologists-urge-obama-map-other-brain***
OHO! FB palautti vuodenn päästä virheellisesti bannaamansa viestin!
Juttu on kuitenkin lukumuurin takana.
https://rdouglasfields.wordpress.com/2013/09/09/map-the-brain-not-just-neurons/
Nyt ne "ovat löytäneet aivot" sukkulamdoltakin...
" science
How MIT cracked the code linking brain and behavior in a simple animal
Researchers from the Massachusetts Institute of Technology have created a detailed map of neuronal activity in C. elegans,revealing how neurons encode behaviour. Using cutting-edge technology, they discovered the ability of neurons to adjust their coding based on different factors and conditions. Their findings provide a comprehensive atlas of neurobehavior for further studies.
Massachusetts Institute of Technology Researchers model and map how neurons in the tiny brain of C. elegans encode its behaviors, revea-ling many new insights into the strength and plasticity of its nervous system.
To understand the complex relationship between brain activity and behavior, scientists needed a way to map this relationship to all neurons in the entire brain. So far this has been an insurmountable challenge. But after inventing new techniques and methods for this purpose, a team of scientists at MIT’s Picauer Institute for Learning and Memory has produced an accurate compu-tation of neurons in the tiny, controllable brain of a humble person. C. elegans A worm, showing how its brain cells encode nearly all of its basic behaviors, such as locomotion and feeding.
In the journal cell on August 21 The team presented new brain-level recor-dings and a mathematical model that accurately predicts the diverse ways neurons represent the worm’s behaviours. Applying this model to each cell specifically, the team produced an atlas of how most cells encode and the circuits in which the animal’s actions are involved. Thus, the atlas reveals the ‘logic’ behind how the worm brain produces a sophisticated and flexible repertoire of behaviours, even as its environmental conditions change.
Insights from the research
“This study provides a global map of how an animal’s nervous system is regulated to control behavior,” said senior author Stephen Flavell, associate professor in MIT’s Department of Brain and Cognitive Sciences. “It shows how many of the specific ganglia that make up an animal’s nervous system encode subtle behavioral features, and how this depends on factors such as the animal’s recent experience and current condition.”
Graduate students Jungsoo Kim and Adam Atanas, who each received their PhDs this spring for research, are the study’s lead authors. They’ve also made all of their data, model results, and atlas freely available to fellow researchers on a website called WormWideWeb.
A 2-minute excerpt from a typical neurological/behavioral dataset. The blue, orange and green dots are targets for tracking, which allowed the team to locate the worm’s head and keep the animal centered. A separate microscope view (not shown) that tracks the synchronous activity of each brain cell. Image credit: Flavell Lab/MIT Picware
Advanced techniques and notes
To make the measurements needed to develop their model, Flavell’s lab invented a new microscope and software system. This setup automatically tracks almost all of the worm’s behavior (moving, feeding, sleeping, laying eggs, etc.) and the activity of every neuron in its head (the cells are designed to flash when calcium ions build up). Reliably distinguishing and tracking dis-crete neurons as the worm wriggles and bends requires writing custom soft-ware, using state-of-the-art tools from machine learning. It has been shown to be 99.7 percent accurate in sampling the activities of individual neurons with a significant improvement in signal-to-noise compared to previous systems, the scientists report.
The team used the system to record the synchronized behavior and neural data from more than 60 worms as they walked around their dishes, doing whatever they wanted.
Data analysis revealed three new observations about neural activity in the worm: Neurons track behavior not only in the present moment, but also in the recent past. They adjust their coding of behaviors, such as movement, based on a surprising variety of factors; And many neurons simultaneously encode many behaviors.
For example, while the behavior of wriggling around a small lab dish may seem like a very simple act,neurons account for factors such as speed, orien- tation, and whether or not the worm is eating.In some cases,they represented an animal’s movement spanning time by about a minute. By encoding recent movement, not just current movement, these neurons can help the worm cal-culate how its past actions affect its current results. Many neurons also com-bine behavioral information to perform more complex maneuvers. Just as a human driver must remember to steer the car in reverse when going in re-verse versus going forward, some neurons in the worm’s brain integrated the direction of movement of the animal and the direction of steering.
By carefully analyzing these kinds of patterns of how neural activity relates to behaviors, scientists have developed C. elegans Probabilistic neural coding model. Encapsulated in a single equation, the model explains how each neuron accounts for different factors to accurately predict whether and how neural activity reflects behavior. Approximately 60 percent of the neurons in the worm’s head are already responsible for at least one behavior.
When fitting the model, the research team used a probabilistic modeling ap-proach that allowed them to understand how sure they were of each approp-riate model parameter, an approach pioneered by co-author Vikash Mansing-ka, a principal research scientist who leads the Probabilistic Computing Project at MIT.
Atlas construction
By creating a model that could quantify and predict how any given brain cell would represent behaviour, the research team first collected data from neu-rons without tracking the specific identities of the cells. But the main goal of studying worms is to understand how each cell and circuitry contributes to be-haviour.So to apply the model’s ability to each of the worm’s specific neurons, all of which had been previously mapped, the team’s next step was to corre-late neural activity and behavior for each cell on the map. Doing so requires naming each neuron a unique color so that its activity can be linked to its identity. The team did this in dozens of freely moving animals, providing them with information about how nearly all of the specific neurons in the worm’s head relate to the animal’s behaviour.
The atlas resulting from this work revealed many insights, complete mapping of the neural circuits that control every animal behaviour. Flavell said these new findings will enable a more comprehensive understanding of how to control these behaviors.
“We were allowed to complete circles,” he said. “We hope that as our collea-gues study aspects of neural circuit function, they can refer to this atlas to get a fairly complete view of the key neurons involved.”
Neuroplasticity
Another key result of the team’s work was the intriguing finding that while most neurons always obeyed the model’s predictions, a smaller group of neu-rons in the worm’s brain - about 30 percent of those encoding behavior - were able to flexibly remap their behavior. , performing fundamentally new roles. Neurons in this group were reliably similar across animals, and were well connected to each other in the worm’s synaptic wiring diagram.
Theoretically, these remapping events could happen for any number of reasons, so the team conducted more experiments to see if they could cause neurons to remap.As the worms wriggled around their plates, the researchers applied a laser zap that heated the agar around the worm’s head. The heat was harmless but enough to disturb the worms for a while, resulting in a change in the animal’s behavioral state that lasted for minutes. From these recordings, the team was able to see that many neurons correctly remapped their behavioral coding when the animals switched behavioral states.
“Behavioral information is richly expressed across the brain in many different forms - with distinct tunings, temporal scales, and levels of plasticity - that fit the specific classes of neurons in the brain. C. elegans neural network,” the authors wrote.
Reference: “Brain-level representations of behavior spanning multiple time scales and states C. elegansWritten by Adam A. Atanas, Gongsu Kim, Xiu Wang, Eric Bueno, McCoy Baker, Dae Kang, Jungyeon Park, Talia S. Kramer, Flossie K. Wan, Saba Pasquillo, Ugur Dag, Elbiniki Kalogeropoulou, Matthew A. Gomez, Casey Estrem, Nita Cohen, Vikash K. Mansingka and Stephen W. Flavell, August 21, 2023, Available Here. cell.
doi: 10.1016/j.cell.2023.07.035In addition to Atanas, Kim, Mansingka, and Flavell, other authors of the paper are Xu Wang, Eric Bueno, McCoy Baker, Dee Kang, Jeongyeon Park, Talia Kramer, Flossy Wan, Saba Pasquello, Ugur Dag, Ilbeneke Kalogeropoulou, Matthew Gomez, Casey Estrem and Nita Cohen.
Research funding sources include National Institutes of Healththe National Science Foundation, the McKnight Foundation, the Alfred P. Sloan Founda-tion, the Picauer Institute for Learning and Memory, and the GPP Foundation.
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Medical education people aware of both clinical neuroanatomy & learning are usually very interested in your work about the brain & PNS when I provide details
Surprising also to me to see how slowly you ideas are diffusing into scientific circles.
There is a clinical trial currently underway at CAMH our big psychiatry centre in Toronto by psychopharmacology prof on minocycline in bipolar depression…..