Issue No. 70 BNA Bulletin Spring 2014 The Voice of British today

Guided by the light Optogenetics and fruit fly behaviour Networking opportunities imaging and schizophrenia

Plus: Synaptic plasticity Hoarding disorder Zebrafish nerve regeneration Babies’ social brain development Contents

News 05 15 22 Message from Neuroscience Plasticity: from the President Summit to network A summary of the As well as the molecular Neuroscience Summit mechanisms of synaptic Cover: Visualising kainate 06 held in April 2013 plasticity, Jack Mellor is receptor distribution in Secretary’s report exploring its impact on hippocampal neurons. neural circuits BNA executive Chief Executive Officer: 16 Elaine Snell 05–11 The evolution of ([email protected]) BNA news and events translational CNS Executive Officer: 24 Cecilia Sheen People and places medicines research The remarkable ([email protected]) Funding and fellowships Developing medicines regenerating fish BNA Bulletin for CNS conditions The regenerative Editor: is hard, says Alan M powers of zebrafish may Ian Jones, Jinja Publishing Ltd Design and production: Palmer, but there are hold clues to human Tess Wood reasons to be optimistic neuroregeneration, says Advertising in the BNA Catherina Becker Bulletin: Contact Cecilia Sheen Analysis ([email protected]) for advertising rates and 26 submission criteria. Copyright: © The British 12 Networking Neuroscience Association. Astrocytes Research opportunities Extracts may be reproduced only in health and Lena Palaniyappan is with permission of the BNA. neurodegeneration using a variety of brain ISSN: 1475-8679 A joint BNA and imaging techniques 18 British Neuroscience Association Biochemical Society Inside a baby’s brain to provide insight into Dana Centre international conference New imaging technology schizophrenia 165 Queen’s Gate South Kensington is shedding light on social London SW7 5HE brain development Tel: +44 (0) 208 166 8713 13 Web: www.bna.org.uk Optogenetics: The British Neuroscience Association is a registered controlling the 19 charity (1103852) and a brain with light Extreme hoarding Et cetera registered company (4307833) A one-day symposium People with ‘hoarding limited by guarantee. organised by the BNA disorder’ accumulate and Oxford Neuroscience possessions so 28-33 excessively their lives The history of the BNA are severely affected (revisited) 14 Neuroscience in Davos Hitting the BNA award winners right notes 20 Colin Ingram (1960–2013) The musical brain The sweet smell of was the theme of the success 2013 BNA Christmas Gero Miesenböck is Symposium using optogenetics to probe fruit fly olfaction and other key aspects of fly behaviour

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Message from the President Dear BNA Members We started 2014 with a bang when we announced that BNA2015 for the BNA2015: Festival of Neuroscience will take place in on 12–15 April 2015. It will be held at the Edinburgh International Conference Centre, EICC, in the Edinburgh centre of that glorious city. Narender Ramnani, who organised the immensely successful 2013 Festival at the Edinburgh will be the location of BNA2015: Festival of Barbican, will again lead in 2015. The call for proposals Neuroscience, due to be held on 12–15 April 2015. generated a flood of great ideas for symposia and Following the great success of BNA2013 at the Barbican plenaries which will showcase some of the in London, a similarly ambitious event will be organised at best neuroscience. Edinburgh International Conference Centre. What makes it a Festival is the public programme Further details will be announced in due course, but of events as well as the science conference, so we are BNA2015: Festival of Neuroscience is likely to include around collaborating with the Edinburgh International Science 50 symposia and workshops and a range of internationally Festival to produce an array of events and activities for recognised plenary speakers. The BNA will again be partnering the public that explore the brain. If you have ideas and with other learned societies to deliver a comprehensive would like to get involved, contact the BNA’s CEO, Elaine scientific programme with an outstanding public Snell ([email protected]). engagement element. See www.bna.org.uk/festival2015 We already have a full year. There will be a symposium for further details. on ‘Optogenetics: controlling the brain with light’ on 3 April at the (see page 13). Gero Miesenböck, a winner of the 2013 Brain Prize, will deliver Brain Awareness Week the plenary lecture. He will also give a public talk at the Museum of the History of Science the evening Multiple activities are taking place across the UK during 10–16 before. In partnership with the Biochemical Society, March 2014 to mark Brain Awareness Week, an initiative a two-day symposium on ‘Astrocytes in health and organised by the Dana Alliance for the Brain. neurodegenerative disease’ will take place in London MakeBelieve Arts, for example, will be taking their ‘Journey on 28–29 March (see page 12). to the Centre of the Brain’ project, supported by the Arts We are delighted that Ruby Wax and Colin Blakemore – Council and , to primary schools across the both Patrons of the BNA – will be ‘in conversation’ at south of England. Several universities, including Nottingham the Sheldonian Theatre in Oxford on 4 June 2014. The and Leicester, are organising open days of talks and conversation between them will be a fascinating insight hands-on activities. into Ruby’s personal experience of depression and Colin’s Brain Awareness Week is a global campaign to increase knowledge of the neuroscience underlying mental illness. public awareness of the progress and benefits of brain research. Details are on page 7. See www.dana.org/BAW/ for details of this year’s events and Our Local Group Representatives continue to actively how to get involved in next year’s initiative. promote the BNA, organising seminars, symposia and public activities. We are grateful to them for all their hard work. If you are not already in touch, you’ll find a list of local groups on our website. The European This is the Year of the Brain, a Europe-wide initiative – and it’s going to be an exciting year for the BNA! Year of the Brain

The European Brain Council has pledged to make 2014 the European Year of the Brain. More than 200 organisations, commercial, academic, charitable and political, have pledged to support the Year of the Brain in Europe in 2014. Numerous luminaries, including BNA President Russell Foster, Colin Russell Foster, President Blakemore and Richard Morris, have also lent their support to the initiative. Further details can be found at bit.ly/LFXTPi.

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Secretary’s Report Supporting our Christmas Symposium. A very useful exchange of opinions members Dear and ideas suggested more ways in which the BNA can reflect the needs and aspirations of its community. The BNA’s support for Thelma Lovick enabled her Key points included greater student involvement and to win her employment tribunal case against the Azimuth/Wikimedia Commons Colleagues Dilated Time/Wikimedia Commons the potential to introduce both lay and undergraduate University of Birmingham. Yes – it’s official: the BNA2015: Festival of Neuroscience membership categories. This would tap into the Dr Lovick, a long-standing member of the BNA, will be held in – cue drum roll – Edinburgh! Programme terrific general interest in neuroscience and a new was dismissed from the university for a technical planning is well underway, with around 50 symposia neuroscience careers leaflet aimed at school students infringement of the Animals (Scientific Procedures) and eight plenary lectures in the pipeline. The scientific and undergraduates, which will be available soon on Act 1986. The BNA helped Dr Lovick through a programme will be just as excellent as it was in London the BNA website. university hearing and appeal processes and, when last year. And, like 2013, a major public engagement As always, BNA HQ is very keen to hear from you, our these were unsuccessful, supported her through programme is also being assembled to run in parallel members. This can be done through your Local Group Rep, an employment tribunal, which threw out the case with the main conference. Make a note in your diaries any Committee or Council member, or the BNA Office. against her in September 2013. One of the criticisms of 12–15 April 2015 for what promises to be another If you do contact the BNA Office, you will probably of the university was that it had not taken account neuroscience spectacular from your BNA. receive a response from Cecilia Sheen (cecilia.sheen@bna. of the experts the BNA and others had made Colin Blakemore and Nancy Rothwell, two leading scientists identified by the Science Council. As you might expect, we’ve also been very busy org.uk). Cecilia is covering for Louise Tratt, who is taking available through the process. Dr Lovick has since with other things. From the ever-popular Christmas maternity leave. We send Louise our best wishes at this taken up a position at the University of Bristol. symposium, featuring music and the brain, to co- exciting time. sponsored meetings with the Biochemical Society and The hot 100 Oxford Neuroscience on astrocytes and optogenetics, respectively, the BNA is pushing the agenda of topics Standing up The Science Council has attempted to dispel the notion that there is a single of interest to our members. Furthermore, public type of scientist, identifying ten leading scientists – including some familiar engagement continues apace with two of our high profile names – in ten categories. Patrons, Ruby Wax and former BNA President Colin for science The list is aimed at groups such as the government, media and the public Blakemore, in conversation later this year in Oxford. who may equate the term ‘scientist’ only with long-gone luminaries or those Never an organisation to neglect its members, your , former President of the BNA, has been making landmark discoveries. The list emphasises that there are many views were once again shared with BNA Council during awarded the 2013 John Maddox Prize for Standing different types of scientist, each making important contributions to wider the Local Group Rep forum held the day after the Bruno Frenguelli, Secretary up for Science. The prize recognises courage in scientific endeavours. Categories cover teaching, entrepreneurship, policy- promoting science and evidence on a matter of public making and communication, as well as discovery. interest, in the face of difficulty and hostility. The ‘investigator scientist’ category includes both Uta Frith and Nancy The award, a joint initiative of the science journal Rothwell, while ‘communicator scientists’ include Colin Blakemore and Nature, the Kohn Foundation, and the charity Hannah Critchlow of Naked Neuroscience fame. Health psychologist Marie Sense About Science, reflects Professor Nutt’s Johnstone (Aberdeen) is named as a ‘developer/translational’ scientist, as commitment to evidence-based debate about drug is specialist Sir Nigel Shadbolt (Southampton) and regulation, often in the face of political opposition. psychologist Andy Young (York). Max Headley (Bristol) is recognised as a The award is named in honour of former Nature ‘policy maker’ scientist for his work on animal use in research. The full list editor, Sir John Maddox. can be found at bit.ly/1auYWHA.

BNA Council and National Committee Wellcome Images

BNA Council National Committee All out-of-copyright historical Wellcome Images Russell Foster (Oxford): President Emil Toescu (Birmingham): Membership Secretary are being made freely available under the Creative John Aggleton (Cardiff): President-Elect Anne King (Leeds): Education and Continuing Professional Development Commons Attribution (CC BY) licence, enabling David Nutt (Imperial): Immediate Past President (CPD) Secretary them to be used and manipulated freely, for Bruno Frenguelli (Warwick): Secretary Attila Sik (Birmingham): Publications Secretary commercial or personal purposes, as long as Duncan Banks (Open University): Treasurer Peter J Brophy (Edinburgh): Professional Society Liaison the original source is acknowledged. Narender Ramnani (Royal Holloway, ): Meetings Secretary Jenni Harvey (Dundee): Equal Opportunities Representative The 100,000 images include numerous Trevor Bushell (Strathclyde): Local Groups Co-ordinator Gary Gilmour (Eli Lilly & Co): Corporate Representative historically important images of the brain and Dimitri Kullmann (UCL): Member of Council Felicity Gavins (Imperial): Early Career Representative nervous system. High-resolution files can be Irene Tracey (Oxford): Member of Council Cecilia Sheen (BNA): Executive Officer downloaded directly from Elaine Snell (BNA): Chief Executive Officer http://wellcomeimages.org From Wellcome Images: 14th and 17th century representations of the brain.

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Events Bristol A platform for dementia of prefrontal cortex in to undergraduate and the hippocampal graduate students, and Researchers at Bristol have taken their ‘Brain Box The MRC has launched the UK Dementias Research Platform (UKDP) behaviour translation, practical skills workshops. Challenge’ to more than 1000 primary school pupils. to promote the use of population cohorts in dementia research. Wikimedia Commons respectively. The Brain Box Challenge is a hands-on practical The UK has outstanding strengths in population cohorts, Edinburgh workshop, helping pupils in years 4–6 understand including the 500,000-strong UK Biobank cohort. Oxford lecture online what the human brain looks like, how scientists As cohort members age, the prevalence of dementia and Neuroscience The Edinburgh study it, how it differs from those of other animals neurodegenerative disease increase. Physiological and other data Symposium Neuroscience 2013 Public and how it controls our behaviour. Organised by Dave collected by the cohorts may provide insight into the development The fifth Annual Oxford Christmas Lecture can Turk, the initiative has been running since October of such conditions (or protection against them). Findings could Neuroscience Symposium now be enjoyed online. 2012, and in September 2013 his department feed into early detection and development of new treatments. will take place on 26 In their presentation, received the STEM University Department of the The UKDP, which will cover 22 cohorts and two million Messing with your head: Kylie Minogue. Neuroscience@ March 2014. As well as ‘Folding and unfolding: Year award for Bristol, Bath and Somerset from participants, is intended to be a public–private partnership, with Nottingham a wide range of local the molecular origami STEMNet. See bit.ly/1kPPloA for more. GSK already pledging its support. Five-year funding of £5m has Music and the masses 1 On 11 December speakers, the Symposium of dementia’, Richard been awarded to a team led by John Gallacher (Cardiff), with an 2013, Nottingham will also include a guest Knight and Jean executive team of investigators from Cambridge, Edinburgh, King’s A new ‘citizen science’ project aims to identify what makes a song lecture from Francesca Manson cover the College London, Imperial College London, UCL and Swansea. A so catchy. Launched at the Manchester Science Festival, #Hooked gathered for the Happé (Institute of misfolding of key brain Rowling clinic £650,000 feasibility study, funded by the MRC and the NIHR, is asked celebrities and members of the public to nominate their annual Neuroscience@ Psychiatry) on autistic proteins, how they lead intensively characterisating 24 pre-clinical Alzheimer’s disease favourite catchy tune. A poll of 700 people concluded that ‘I Can’t Nottingham Poster spectrum disorders. to disease, and how a The Anne Rowling Regenerative Clinic at patients, to try to identify early biomarkers of disease. The project Get You Out of My Head’ by Kylie Minogue was the catchiest and Lecture Day. better understanding the University of Edinburgh was formally opened by is being led by Simon Lovestone (Oxford and King’s College London) ever. Wellcome Trust Engagement Fellow Erinma Ochu and More than 50 posters UCL of misfolding may Her Royal Highness, The Princess Royal in October in collaboration with the Imanova brain imaging partnership. See computational musicologist John Ashley Burgoyne aim to analyse presented neuroscience Neuroscience ultimately lead to new 2013. The centre is named after the mother of bit.ly/1dBeSfu for more on the UKDP. the selected songs to try to find the roots of their catchiness. research from across Symposium treatments. The lecture author J K Rowling, who provided a £10m donation. As well as a simple ‘name-that-tune’ game for the web, the the University of The 2014 UCL can be viewed at bit. Anne Rowling died from multiple sclerosis in 1990. team hopes to provide insight into the aspects of music that Nottingham’s Schools Neuroscience ly/1gUK6OF. See http://annerowlingclinic.com/ for more about Dementia funding appeal to the brain, potentially feeding into musical therapies for of Life Sciences, Symposium will take the centre. neurodegenerative or other conditions. See bit.ly/19zk44c for more. Bioscience, Psychology, place on Thursday 19 Glasgow The ESRC and NIHR have awarded £20m funding for six Physics, Mathematics June at the Institute Neuroscience day dementia research programmes designed to slow or prevent and Medicine, and the of Education. The The 5th Glasgow Nudge-it the development of dementia and improve the quality of life of Music and the masses 2 MRC Institute of Hearing symposium is only open Neuroscience day, held dementia patients and their carers. Research, covering to members of the UCL at the University of John Menzies and Gareth Leng (Edinburgh) have The ‘Neighbourhoods and Dementia’ programme, led by The MRC is launching a mass participation study to assess topics ranging from Neuroscience community Strathclyde, took place been awarded an €8.9m EU Framework Programme John Keady (Manchester), will explore what makes a ‘dementia- whether listening to loud music is contributing to increased cellular neuroscience and invited guests. The on 17 January 2014. A 7 (FP7) grant for an international collaborative friendly neighbourhood’. The ‘Promoting Independence in hearing loss in the UK population. to cognitive and clinical day’s programme will be keynote address on study of the determinants of food choice. ‘Nudge- Dementia (PRIDE)’ study, led by Martin Orrell (UCL), aims to Around 1 in 6 people have some form of hearing loss, sufficient neuroscience. Guest announced shortly. imaging pain was given it’ will bring together an interdisciplinary team of identify how social and lifestyle changes can reduce the risk of to cause difficulties with communication, with numbers rising by speaker Joanna Wardlaw by Irene Tracey (Oxford). dozens of scientists from 16 institutions across six developing dementia and disability. some 12 per cent over the past 20 years. Listening to amplified (Edinburgh) gave a Barts European countries, the USA and New Zealand. Gillian Livingston (UCL) is leading a ‘Managing Agitation and music could be contributing to this increase. fascinating overview Neuroscience Cambridge The aim is to better understand decision-making Raising Quality of Life’ programme, while Martin Knapp (London Michael Akeroyd from the MRC Institute of Hearing Research of her multidisciplinary Queen Mary and Barts Neuroscience in food choice and to build predictive models to School of Economics and Political Science) will be developing a tool and colleagues are asking people to go online, describe their translational research and the London (QMBL) Seminar contribute to public health policy. to identify the future needs of dementia patients and their carers. listening habits and take a short hearing test. The results programme on vascular Neuroscience Society The 26th Cambridge The ‘Living well with Dementia’ study, being led by Linda Clare should reveal any correlations between past listening habits disorders of the brain. organised a one-day Barts Neuroscience Seminar, (Bangor University), will examine the factors that help dementia and current hearing difficulties. The test can be taken at Postgraduate poster Neuroscience symposium 14 March, sponsored Brain injury award patients maintain their quality of life. Finally, ‘Seeing what they www.100yearsofamplifiedmusic.org/. prizes were awarded to on 12 February 2014. by the BNA, focuses see’, led by Sebastian Crutch (UCL), will focus on posterior cortical Beili Shao (Division of The student-led event on ‘Brain science and David Menon (Cambridge) and Andrew Maas atrophy, which particularly affects vision. Clinical Neuroscience, featured a stellar lineup mental health’. The (Antwerp) are leading a £25m Europe-wide More games Stroke Group) and Sorley of speakers, including Seminar features investigation into the causes of and treatments for Somerled (School of David Nutt, Daniel plenary lectures from traumatic brain injury. Data will be analysed from Leonard Wolfson Centre opens Four new games have been added to the Great Brain Experiment Psychology, Behavioural Wolpert (Cambridge), Mark Johnson (see page more than 5000 patients recruited from across app, a ‘citizen science’ project using mobile phone games to gather Neuroscience Group), for Richard Frackowiack 18) and Trevor Robbins, Europe, providing detailed insight into the scale of The Leonard Wolfson Experimental Neurology Centre at UCL information on psychological and cognitive tests. Developed by a their excellent research (Lausanne), David with an evening public such injury in Europe, differences in treatment and has been formally opened. Funded by a £20m award from the team at the Wellcome Trust Centre for Neuroimaging and White and presentations on the Clayton (QMUL) and plenary lecture by best practice in identification and treatment. The Wolfson Foundation, the Leonard Wolfson Centre has been set Bat Games, the new games will test decision-making, performance effects of hyperglycaemia Nick Fox (UCL). The Michael Owen (Cardiff) investigation is part of the International Traumatic up to improve understanding of neurodegenerative diseases and under pressure, hearing ability and use of information to make on cerebral barrier meeting also included a on ‘Genes, brains and Brain Injury Research initiative, running in the USA, to provide facilities in which experimental therapeutics can be predictions (see BNA Bulletin 69, Autumn 2013). function and on the role poster competition open psychiatry’. Canada, and elsewhere. tested in humans (see BNA Bulletin 66, Autumn 2012). See www.thegreatbrainexperiment.com

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News in Brief Wellcome Trust Investigators Neuroscience at Davos Neuroscientists again feature in the New Investigator and Senior Investigator Cambridge Barbara Sahakian awards recently announced by the Wellcome Trust: joined world leaders and other dignitaries at the Davos World Economic Forum in January. Every New Investigators year, leading thinkers from business, politics, Christopher Petkov (Newcastle): Neuronal mechanisms for extracting academia and other sectors gather at Davos to communication signals and signalling sequences: From animal models to humans. discuss how to improve the state of the world. The theme of this year’s meeting was ‘The Senior Investigators Reshaping of the World: Consequences for Society, Jonathan Clarke (King’s College London): Cellular and molecular regulation of Politics and Business’. Professor Sahakian was a early brain development. discussion lead in sessions on the neuroscience of Leon Lagnado (Sussex): Synaptic computation in the visual system. leadership, performance-enhancing technologies Walter Marcotti (Sheffield): The development and function of the mammalian and redefining ageing. See page 31 for more. auditory circuitry. Kate Storey (Dundee): Cellular and molecular mechanisms regulating neuronal Neuroscience research may find application in the classroom. FENS on film differentiation in embryos and adults. Budding film-makers might like to enter a video Retinal section, by Sasha Woods. Neuroscience in education competition being run by FENS in association with the FENS Forum, ‘Jump the FENS’, to be held in Royal Society fellowships The Wellcome Trust and the Education Endowment Foundation (EEF) have Milan 5–9 July 2014. €750 prizes are available for Art of science launched Education and Neuroscience, a £6m fund to support collaborations there categories – protocol videos, educational Neuroscience features in several fellowship projects recently funded by the between educators and neuroscientists to develop and evaluate neuroscience- presentations and for humorous entries. Entrants Royal Society. Neuroscience made a strong showing in Bristol’s based educational interventions. must include at least one PhD or postdoctoral annual Art of Science competition, with Sasha A better understanding of brain function, and how students learn, offers student registered for the FENS Forum. The Royal Society University Research Fellowship Woods one of the runners for this beautiful retinal the prospect of improved teaching methods. Indeed, an online survey of closing date for entries is 30 April 2014. Further (providing potential leaders with the opportunity to build an independent section. The winning images were turned into a teachers carried out by the Wellcome Trust found that many teachers were details can be found at www.jumpthefens.eu/ research career): 2014 calendar. Winning entries can be viewed at optimistic about the ability of neuroscience to improve future teaching video-contest.html • Brian Patton (Oxford): Imaging deep tissue neural processes with bit.ly/1cDol2n. practice. However, some supposedly ‘scientific’ innovations, such as the belief nanodiamond. in different learning styles and commercially developed interventions such as Music all in the mind Brain Gym, have little evidence to support them. The Christmas Eve edition of BBC Radio 4’s All in Newton International Fellowship To support the initiative, the EEF and Wellcome Trust have carried out a the Mind, presented by Claudia Hammond, drew (sponsored by the Royal Society and the British Academy): Louisa Gross literature review, examining the impact of educational interventions based on inspiration from the BNA Christmas Symposium. • Sungho Tak (South Korea to UCL): Dynamic causal modelling for neuroscience, surveyed teachers and parents to understand their perspectives, The 30-minute programme featured speakers near-infrared spectroscopy. and approaches they are already using, and commissioned a series of from the symposium – hear the results at bbc. • Rafael Pineda Reyes (Spain to Edinburgh): Kisspeptin neurones: linking Horwitz Prize articles from neuroscientists (see the Wellcome Trust’s ThInk blog, http:// in/1cp3ejp. reproduction with behaviour. thinkneuroscience.wordpress.com/). • Takao Sasaki (Japan to Oxford): From individual cognition to collective intelligence. John O’Keefe has been awarded Columbia See bit.ly/LfhW6n for further details. The deadline for the first round of Naked neuroscience University’s 2013 Louisa Gross Horwitz Prize, applications is 6 May 2014. David Nutt joined Hannah Critchlow for a special Dorothy Hodgkin Fellowship alongside Edvard Moser and May-Britt Moser. Christmas Naked Neuroscience podcast. Professor (helping early-career researchers who require a flexible working pattern Professor O’Keefe, Director of the Sainsbury Nutt chose some of his favourite neuroscience progress to a permanent academic position): Wellcome Centre for Neural Circuits and Behaviour Authentic Biology in schools stories from 2013, featured alongside items • Sebastian Cachero (Cambridge): Transynaptic labeling of neural circuits in at UCL, was recognised for his landmark work on of laughter and addiction. The November 2013 Drosophila. spatial maps within the hippocampus. Students from five secondary schools presented the results of academic podcast was a more sombre affair, ‘Bombing the research they had undertaken at a symposium featuring BNA President Russell Brain’ examining the impact of war on mental Charles Fernyhough’s Pieces of Light: The New Science of was runner Foster and Lord Winston. health and the potential for brain enhancement up in 2013 Royal Society Winton Prize for Science Books. Described by Ian The students have been participating in the Wellcome Trust’s ‘Authentic and brainwashing. Podcasts can be downloaded Sample in the Guardian as “utterly fascinating and superbly written”, the book Gabbay Award Biology’ initiative, which teams up schools with nearby universities enabling from bit.ly/12NaQuZ. focuses on reconstructive aspects of memory, combining science and memoir. students to carry out genuine experimental research. Supported by a Wellcome Gero Miesenböck (Oxford; see page 20) is one of Trust Society Award, Authentic Biology was piloted by Dave Colthurst at the Writing on the brain this year’s recipients of the Jacob Heskel Gabbay Simon Langton Grammar School for Boys, who worked with researchers at the PhD student Scott Armstrong (Imperial College Neuroeconomics accolade Award in Biotechnology and Medicine. The award, University of Kent on a project focused on myelin basic protein. The scheme London) won the 2013 Max Perutz Science Writing created by the Jacob and Louise Gabbay Foundation, has now been extended to five schools, linked to the Universities of Bristol, Award for his article ‘Saving the brain from itself’. Timothy Behrens (Oxford) has received the 2013 Young Investigator Award recognises scientists in academia, medicine or Sheffield and Southampton and Queen Mary, University of London. He received a prize of £1500 and his essay was from the Society for Neuroeconomics for his work on brain function in decision- industry whose work has outstanding scientific The results form the research projects were presented at a second annual published in Times Higher Education. making (see BNA Bulletin 68, Summer 2013). Professor Behrens shared the content and significant practical consequences in Authentic Biology Research Symposium on 4 November 2013. The Kent award with Daphna Shohamy from Columbia University in New York. biomedical sciences. collaboration also hopes to publish its results in an academic journal.

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disrupted in neurodegenerative diseases. symposium will hear how researchers have Astrocytes in health The ‘Astrocytes in health and used optogenetics to address biological neurodegeneration’ conference problems in a range of experimental model brings together leading researchers organisms. Speakers include: and neurodegeneration investigating the role of astrocytes in • Ole Paulsen (Cambridge): Using health and astrocyte dysfunction in optogenetics to probe left–right The BNA and Biochemical Society have joined forces to organise an neurodegenerative diseases. As well as asymmetry of hippocampal memory international conference on astrocytes and their role in health and relatively well-studied neurodegenerative • Stephanie Cragg (Oxford): Illuminating disease, to be held on 28–29 April 2014. conditions such as Alzheimer’s disease the gatekeepers of dopamine and motor neuron disease, it will also transmission provide a forum for researchers working on • Vincent O’Connor (Southampton): Astrocytes, the most abundant cell the progression of neurodegenerative lysosomal storage disorders, including rare Guiding light to feeding behaviour in in the human brain, have traditionally diseases. Research in this area has neurodegenerative diseases of childhood C. elegans been viewed as ‘support cells’ and given traditionally focused on microglia, such as the neuronal ceroid lipofuscinoses. • Claire Wyart (Paris): Dissecting significantly less attention than neurons. considered to be the major immune cell in Topics include: spinal circuits underlying sensory Recent years have seen a resurgence of the brain. However, in the past few years, • Astrocyte–neuron interactions motor integration with light in a interest in astrocytes and other glial cells, deficits in the function of astrocytes are • Astrocytic signalling pathways small vertebrate with the growing realisation they not only increasingly recognised to be associated • Energy metabolism and astrocytes • Alexander Gourine (UCL): Studying contribute to normal brain function but also with neuronal loss in motor neuron • Neuroinflammatory responses the function of vital circuits using play significant roles in brain disease. The disease, Alzheimer’s disease and some of astrocytes optogenetics joint BNA–Biochemical Society conference, rare lysosomal storage disorders. • Astrocyte dysregulation in brain injury, • Sergey Kasparov (Bristol): Application of featuring speakers from the UK, In addition, there is now substantial Alzheimer’s disease, lysosomal storage Optogenetics: controlling opsin-based actuators to study astrocyte- Continental Europe and the USA, will cover evidence that astrocytes regulate normal disorders, and motor neuron disease. to-neuron communication emerging research in these areas, with a neuronal activity and connectivity, Speakers include: • Dimitri Kullmann (UCL): Optogenetics for particular focus on neurodegeneration. playing important roles in basal synaptic • Alexei Verkhratsky (Manchester) the brain with light closed loop control of neural activity. The biochemical mechanisms transmission and long-term potentiation. • Andrey Abramov (UCL) underlying the development and Major research efforts are ongoing to • Dmitri Rusakov (UCL) A one-day symposium on optogenetics, organised by the BNA and A plenary lecture will be given by keynote progression of most neurodegenerative understand the signalling pathways • Mark Sands (University of Washington, USA) Oxford Neuroscience, will showcase some of the ways in which this speaker Gero Miesenböck, Director of the diseases remain unknown. It has by which astrocytes and neurons • Michael Sofroniew (University of powerful new technique is being used to study nervous system function. Centre for Neural Circuits and Behaviour become increasingly clear that signalling communicate, and the mechanisms by California Los Angeles, USA) at the University of Oxford, who will be between glia and neurons influences which astrocyte–neuron interactions are • Milos Pekny (University of Gothenburg, introduced by Colin Blakemore (School of Sweden) In 2013, Gero Miesenböck of the University sensitive ion channel (nowadays typically Advanced Study, University of London). • Nicola Allen (Salk Institute, USA) of Oxford and five other researchers channelrhodopsin, originally identified in The symposium will be chaired by BNA • Pamela Shaw (Sheffield) were awarded the prestigious Brain Prize algae) in specific subsets of neurons. A President Russell Foster. Sponsorship Gerry Shaw • Pierre Magistretti (University of 2013, endowed by the Grete Lundbeck light signal can then be used to stimulate has been provided by the International Lausanne, Switzerland) Foundation, for their development of neural activity in these specific neurons. Brain Research Organization, Laser 2000, • Siddharthan Chandran (Edinburgh) optogenetics. To mark this achievement, The technology has distinct Tracksys Microscope Services Ltd, CoolLED • Vladimir Parpura (University of the BNA and Oxford Neuroscience advantages over conventional methods and Laser Quantum. Full details of the Birmingham Alabama, USA) have teamed up to organise a one-day of electrode-based stimulation. For a symposium can be found at bit.ly/1hhL9c5. • Yuriy Pankratov (Warwick) symposium, ‘Optogenetics: controlling the start, it is possible to work with large • Jon Cooper (King’s College London) brain with light’, to be held on 3 April 2014, numbers of cells – far more than would be Ruby Wax in conversation with which will showcase how groups in the possible with electrode-based approaches. Colin Blakemore Plenary lectures will be given by Michael UK and elsewhere in Europe are using the In addition, genetic control elements Wednesday 4 June, 19.00-20.30 Sofroniew (University of California Los technology to explore neural function. are used to limit the expression of the Sheldonian Theatre, Oxford Angeles, USA) and Alex Verkhratsky The symposium has been designed light-sensing mechanism to specific cells (Manchester). to give graduate, postgraduate and other in a population, without each individual Join TV personality Ruby Wax in The conference will take place at the early-career researchers a sense of how cell needing to be identified in advance. conversation with Colin Blakemore. UCL Institute of Child Health on Guilford optogenetics can be used to address Furthermore, the technique is far more This discussion will explore the many Street in Central London. Conference biological problems, and to inspire them flexible than electrode-based methods – ways in which neuroscience has come sponsors include Portland Press Ltd, to think how they might apply the precise neuronal control is possible even if to play such an integral part in Ruby’s Biochemical Society Transactions and ASN technology in their own studies. a behaving animal moves around. life and career. We also learn how she Neuro, and proceedings will be published Optogenetics provides a powerful These technical advantages have overcame depression, and find out how in Biochemical Society Transactions. way to selectively activate (or inhibit) opened up multiple new opportunities to a neuroscientist views mental illness BNA members can benefit from groups of neurons in living, behaving identify neural circuits and to probe their from Professor Blakemore. A thoroughly reduced registration rates. Full details organisms. First reported by Professor properties in living organisms. In recent insightful evening not to be missed. of the conference can be found at Miesenböck in 2002 (see page 20), it relies years, the technology has been refined Details will be on the BNA website shortly. An astrocyte grown in tissue culture. bit.ly/1eFNJsc on genetic methods to express a light- and widely adopted worldwide. The

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Hitting the right notes Thanks to the ubiquitous carols (and, inevitably, Slade), the musical brain was the appropriately seasonal theme of the 2013 BNA Christmas Symposium, held in partnership with the Sainsbury Wellcome Centre at UCL.

Russell Foster outlining the BNA’s vision. In a richly varied programme, Maria coordinating group activities or promoting Uta Frith receiving her award. Chait (UCL) opened proceedings with a pro-social behaviour. applications. In the research arena, fascinating insight into how the brain’s One of music’s most striking there was widespread support for more auditory system can detect patterns in qualities is its ability to trigger strong emphasis to be put on interdisciplinary sound – an ability fundamental to the emotional responses in listeners – a research and collaboration – between appreciation of music. Not only are we power instinctively exploited by film- disciplines and across institutions. remarkably quick at detecting patterns makers and others. Alan Watson (Cardiff) There were also calls for greater in series of notes – typically by about the discussed the brain systems involved in interactions between academia and fourth note in a repeating pattern – but we these responses, particularly emotional industry, recognising the complementary also seem to do so automatically. These brain networks. Given its lack of any clear skill sets in the two sectors. Industry has pattern-recognition skills, suggested Dr evolutionary purpose or advantage, it is Speakers at the BNA’s Neuroscience Summit. retreated from the field and more needs Chait, may have evolved to enable us to curious that music taps so powerfully into to be done to entice additional commercial predict what is coming up and to rapidly emotional and reward pathways, and is Jane Haley with Russell Foster. investment. Nevertheless, significant spot deviations from expectations. capable of generating such pleasing and Neuroscience Summit efforts are being made, particularly Katie Overy, Director of the Institute even intense emotional responses. unable to express his musical ideas in through industrial–academic consortia and for Music and Human and Social Lauren Stewart (Goldsmith’s, later life. Brain imaging is now revealing The BNA has published a report of the Neuroscience Summit, held partnerships to tackle difficult problems Development in Edinburgh, brought an University of London) focused on an the neuroanatomical correlates of highly at the Royal Society in April 2013, outlining some of the ways in which collaboratively. Sharing more information interdisciplinary perspective to the day. unusual condition, congenital amusia. specific deficits in musical cognition the BNA can play its part in tackling the huge challenges posed by in the public domain and ‘open innovation’ One of her main interests is the ‘rhythmic People with this condition, she suggested, in different patient groups. More disorders of the brain and nervous system. approaches can avoid duplication of efforts, brain’ and the curiously powerful effects cannot make sense of music; they cannot generally, he suggested that music promote coordinated, concerted efforts of regular rhythms or beats. Rhythmicity recognise familiar tunes and may even may have evolved as a mechanism for to understand disease mechanisms, and appears to have a powerful influence on find music unpleasant to listen to. She communicating complex mental states, The Neuroscience Summit, a joint venture Research Charities on public and patient accelerate drug development processes. the body, while many human behaviours has recruited a group of Londoners with supporting the remarkable social cognition between the BNA, the European College involvement in research. John Perry, John Even so, more needs to be done to show striking rhythmicity (including characteristics of congenital amusia, skills of humans. of Neuropsychopharmacology (ECNP) Williams and Melanie Welham provided promote interdisciplinary and cross- clapping, as readily demonstrated by finding intriguing evidence that their During the symposium, presentations and the European Brain Council (EBC), a funders’ perspective, from the Medical sectoral working. More ways to encourage audience participation). Perhaps, Dr Overy difficulties may not be a simple perceptual were also made to the year’s BNA brought together neuroscientists, leaders Research Council, Wellcome Trust, and and reward working in partnership need to speculated, the power of beats may have abnormality – their tonal perception award winners – Uta Frith (contribution from research councils, industry and Biotechnology and Biological Sciences be developed, and career paths for young deep-seated roots, as a mechanism for skills are generally near-normal– but to neuroscience), Jane Haley (public patient organisations to take stock of UK Research Council, respectively. Industry scientists to reflect contributions to team may actually reflect a lack of awareness understanding of neuroscience), Rumana neuroscience and how it can best address views were represented by Jackie Hunter of working as well as individual achievement. of these skills. Hence congenital amusia Chowdhury (postgraduate award; see the health and social consequences of OI Pharma Partners and Gary Gilmour of Lilly Other incentives may be needed to may be a meta-cognitive rather than page 32) and Elina Jacobs (undergraduate brain disorders. It was supported with a UK. Colin Blakemore and David Nutt brought encourage further industrial investment, perceptual deficit. award; see page 32). grant from the Federation of European an academic perspective, while Richard while the European regulatory framework In a break from academic As well as the stimulating scientific Neuroscience Societies (FENS). Morris and Trevor Robbins helped to draw needs to be re-examined to ensure that presentations, Peter Todd described the presentations, participations were treated As outlined in an analysis out the day’s conclusions. The summit was unnecessary regulation does not slow Alzheimer’s Society’s ‘Singing for the to virtuoso violin playing during intervals commissioned by the EBC, brain disorders introduced by BNA President Russell Foster down the development of new medicines. Brain’ service, in which trained musicians by Jinpo Xiang, a sixth-form student from are responsible for an enormous health and and chaired by BBC Radio’s Quentin Cooper. The discussions and themes have been run regular workshops for people with Newcastle under Lyme. And during post- economic burden in Europe – amounting The importance of the subject was refined into a series of action points. The dementia and their careers. Based on ‘old- talk mince pies and wine, entertainment to some €800bn every year. At the same underlined by messages of support from BNA is now working on how these action time’ songs, the stimulating and hugely was provided by the Rhapsody in time, technological advances and a greater both the Prime Minister, David Cameron, points can best be taken forward. The aim enjoyable sessions provide a boost to both Bluegrass ensemble, Kelly Jakubowski and understanding of the brain are opening up and the Minister of State for Universities is to ensure not just that the UK retains memory and wellbeing. Steven Lyons. The highlight of the day, new opportunities for interventions. A key and Science, . its position as one of the world leaders in Finally, Jason Warren (UCL) explained though, may have been BNA President challenge is how to ensure this potential A number of key themes emerged neuroscience research but also that this how neurodegeneration can have highly Russell Foster’s Christmas cracker jokes – is realised to the benefit of the citizens of from the meeting. Patients were seen to intellectual potential is fully exploited to specific effects on musical perception some of which, fortunately, have been Europe (and beyond). have a potentially vital to play throughout help those affected by debilitating and and appreciation. The composer Ravel, captured for posterity in the Guardian’s The summit heard presentations the research process, from feeding into deadly brain disorders. for example, who probably suffered feature on scientists’ favourite jokes from the EBC’s Mary Baker and Sharmila policy-making and priority-setting to A copy of the Neuroscience Summit Lauren Stewart at the Christmas Symposium. from frontotemporal dementia, became (bit.ly/1bBRB89). Nebhrajani of the Association of Medical advising on research protocols and grant report can be downloaded at bit.ly/1crbSgU.

14 BNA Bulletin Spring 2014 www.bna.org.uk www.bna.org.uk Spring 2014 BNA Bulletin 15 Analysis Analysis The evolution of translational CNS medicines research Developing medicines for CNS conditions is even harder than non-CNS drug development, but there are reasons to be optimistic, says Alan M Palmer. Alan M Palmer.

Traditionally, scientific research has been human disorders (to permit the discovery a Translational CNS Summit was held in categorised as either fundamental, driven of a tractable molecular target for drug London on 22–24 October 2013, organised by scientific curiosity (and without any discovery); (2) lead generation and by Hanson Wade (Ref. 5). A number of obvious practical value), or applied – optimisation (the ‘hit’ molecules that encouraging themes emerged: designed to solve practical problems. bind to the molecular target are subjected • Target identification: The development Fundamental and applied researchers to a battery of tests to assess whether of new drugs for CNS disorders has occupy different worlds, possess distinct they are likely to be safe and effective been hampered by poor knowledge of Figure 1. The components and process of translational medicines research. cultures and respond to different drivers. in humans); and (3) clinical testing, to underlying pathophysiology. However, In the medical domain, this makes it meet the safety, quality and performance molecular genetic data are now helping and stratification, and potentially National Institute for Health Research 1. Palmer AM, Sundstrom L. Translational medicines difficult to translate fundamental research standards laid down by regulatory to change this situation. For example, significantly smaller sample sizes. and the Technology Strategy Board, research. Drug Discov Today. 2013;18(11–12):503–5. 2. Palmer AM, Alavijeh MS. Translational CNS medicines results into practical applications that authorities (Ref. 2). genome-wide scans are revealing They also provide opportunities to track as well as from new European funding research. Drug Discov Today. 2012;17(19–20):1068–78. enhance human health and well-being. Translational medicines research mutations and rare copy number disease progression, and hence the vehicles, such as Horizon 2020 (nearly €80 3. Collins PY et al. Grand challenges in global mental health: To help bridge this gap, the concept of is an increasingly important aspect variants that (rarely) cause or increase impact of medicines, over convenient billion of funding available over 7 years) integration in research, policy, and practice. PLoS Med. 2013;10(4):e1001434. translational research was proposed of neuroscience, particularly as 13 per the risk of a CNS disorder. Such data timeframes (Ref. 9). and the Innovative Medicines Initiative 4. Tufts Center for the Study of Drug Development. Pace of in 1968 and has led to the concept of cent of the global burden of disease can lead to the creation of mouse (IMI). IMI is a joint initiative between the CNS drug development and FDA approvals lags other drug ‘translational medicines research’ (Ref. 1). is attributable to mental, neurological models that can be used to facilitate the Future prospects European Federation of Pharmaceutical classes. Tufts CSDD Impact Reports. 2012;14(2). and substance abuse disorders, greater discovery of new drug targets (Ref. 6). CNS translational medicines research is in Industries and Associations and the 5. Palmer A. Translational CNS Summit. Drugs of the Future 2014;39(2):165–70. From knowledge to medicine than both cardiovascular disease and • Animal models of CNS disorders: The the midst of major change. Unfortunately, European Commission. With a budget of 6. Fejgin K et al. A mouse model that recapitulates cardinal The essence of translational medicines cancer (Ref. 3). This burden will increase predictive validity of animal models UK medical charities, which account for €2 billion, it is driven by industry through features of the 15q13.3 microdeletion syndrome including research is the efficient and effective substantially, as the number of people of CNS disorders is generally poor. For one-third of all public expenditure on the identification of bottlenecks to schizophrenia- and -related alterations. Biol Psychiatr. 2013 [Epub ahead of print]. conversion of biomedical knowledge in the world aged over 65 years is set to example, despite the tremendous medical and health research, typically which research can contribute solutions 7. van Dam EA et al. An automated system for the into new medicines. It encompasses rise sharply and the incidence of many advances in transgenic animal exclude medicines research companies and research areas of common interest recognition of various specific rat behaviours. J Neurosci all research activity from fundamental brain disorders (e.g. Alzheimer’s disease, technology (especially for research from applying for funding. By doing so, that reduce drug development times Meth. 2013;218(2):214–24. 8. Oomen CA et al. The touchscreen operant platform for biology to a marketed drug (Fig. 1). stroke and Parkinson’s disease) increases into Alzheimer’s disease), the success they are rejecting the very organisations – and costs. An example is the Pharma- testing working memory and pattern separation in rats and Key aspects of this process are: (1) exponentially after age 65. rate for CNS drug candidates in clinical biotech companies – with the know-how Cog project, which aims to develop and mice. Nature Protocol. 2013;8(10):2006–21. understanding the biological basis of However, developing therapies for development has not increased. to translate research into tangible validate new tools to test candidate drugs 9. Palmer AM. The utility of biomarkers in CNS drug development. Drug Discov Today. 2013. [Epub ahead of print]. disorders of the brain is notoriously However, the use of automated systems patient benefit. for the treatment of the symptoms of 10. Dixon J et al. Medicines discovery in the 21st century: difficult. CNS drugs take on average (including touchscreen technologies) to Important exceptions are Cancer Alzheimer’s disease, as well as compounds the case for a stakeholder corporation. Drug Discov Today. 35 per cent longer than other new analyse rodent behaviour, coupled with Research Technology and the Wellcome that slow disease progression. 2010;15(17–18):700–3. prescription medicines to complete the use of rodents genetically modified Trust. These world-leading organisations These and other translational medicines clinical trials and receive regulatory to reflect risk genes for particular CNS illustrate what can be achieved outside research initiatives (including MRC Technology) Alan M Palmer is a neuroscientist and entrepreneur. Wikimedia Commons approval (Ref. 4). CNS drug candidates phenotypes, is likely to generate animal of traditional pharmaceutical business reflect a new paradigm for medicines research, Currently he is a visiting Professor at UCL and the University of Reading; Life Science Entrepreneur in Residence at the are also less likely than their non-CNS models with better predictive validity constructs, particularly for early stage based on open and integrated partnerships University of Bristol; a director of Cerebroscience Ltd, counterparts to become medicines. As a (Refs 7, 8). translational medicines research. New with wider stakeholder involvement (Ref. 10). MS Therapeutics Ltd and One Nucleus Ltd; and result, several pharmaceutical companies, • The use of biomarkers in clinical public–private partnerships are also With individuals from industry joining their non-executive director of Neuro 360 Ltd and the BNA. including AstraZeneca, Pfizer, GSK, studies: A biomarker can be defined as a evolving where risks and resources are ranks, universities will play an increasingly Merck and Sanofi, have substantially biological variable that has a statistically shared among several participants. Good important part in this process. Academic drug reduced their CNS drug discovery and significant relationship with parameters examples include the Division of Signal discovery is now well established in the USA, development efforts in the UK of disease states or the activity of a Transduction Therapy in Dundee and as illustrated by bodies such as the Academic and overseas. drug or drug candidate. They have great the Structural Genomics Consortium Drug Discovery Consortium, which has 98 In an attempt to discover and develop value in clinical trials. They allow for in Oxford. member universities across North America approaches to improve the speed, more homogenous patient populations Translational research funding is also (www.addconsortium.org). Similar trends are Developing CNS medicines is a challenge. efficiency and effectiveness of CNS R&D, in clinical trials through patient selection available from organisations such as the likely to be seen in the UK.

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compensating for innate vulnerabilities. home- and interview-based research puts Inside a baby’s brain “There’s quite a lot of interest in what Extreme hoarding the figure at around 1.5 per cent. those compensatory factors might Nevertheless, he adds, very little is A new imaging technology is shedding light on social brain development be,” says Professor Johnson. “If you A surprisingly large number of people accumulate possessions so known about the condition: “These are in babies – and revealing remarkably early abnormalities in infants at can understand them, you might excessively that their lives are severely affected – victims of the newly early days: it’s a new disorder, we’re only risk of autism. have a better chance to develop new defined ‘hoarding disorder’. just beginning to understand it.” It has interventions.” Professor Johnson has been linked to some behavioural traits, been involved in a trial of an intervention such as indecision, procrastination and, designed to enhance parents’ social David Mataix-Cols is a specialist in superficial similarities with the hobby of perhaps oddly, perfectionism. Some interactions with their babies, the results obsessive-compulsive disorder (OCD) and collecting. Many healthy people do this, preliminary brain imaging studies have of which are due to be published later related conditions. Although the condition and it’s a highly pleasurable and very social pointed to possible involvement of the in 2014. can be treated reasonably well, he noticed activity. That is in sharp contrast with ventromedial prefrontal cortex, cingulate The work may also shed more light that one group of patients responded hoarding disorder, which involves extreme cortex and limbic structures. Twin studies on the developmental mechanisms of suboptimally: “About 15 years ago I difficulty with parting with possessions.” suggest a moderate level of heritability. autism, says Professor Johnson: “There’s discovered, by chance, that patients who Accumulation of objects, and an inability Its environmental origins are also still a big debate about whether these have OCD and also hoard don’t respond to discard them, ultimately has a obscure. “We know there is a very high young babies have problems because they so well to conventional evidence-based significant impact on people’s lives: “The level of self-reported trauma,” says Dr have some sort of social brain network treatments for OCD. And that triggered a end product is severely cluttered living Mataix-Cols. It might be expected that problem, or whether social stimuli are number of studies to try to understand why.” spaces, to the extent that they are no material deprivation when young might more spatiotemporally complex, and His subsequent work, carried out at longer usable.” The condition is socially be a risk factor: “But that doesn’t seem thus some more widespread cortical the Institute of Psychiatry, and other isolating and distressing for patients and to be the case. These patients were not synapse problem is revealed better by studies showed that, although excessive their families. worse off as children in terms of material social stimuli.” accumulation of possessions can be a A cluttered living space is not necessarily possessions. So that intuitive link does not Recently, Professor Johnson has consequence of OCD, most hoarders were indicative of hoarding disorder, points out Dr seem to hold.” NIRS has revealed differences in the brain responses of infants at risk of autism to social stimuli. even applied NIRS to newborns – in quite distinct from other OCD patients – in Mataix-Cols: “It could be the end product of Interestingly, although patients are collaboration with colleagues in Italy, terms of symptoms and behaviour, brain dementia or schizophrenia or other severe typically diagnosed in middle age, this The biological roots of autism remain of Engineering to adapt a form of optical where mothers typically stay longer activity, and genetics. Dr Mataix-Cols and mental disorders or even the consequences might be the end point of a much longer poorly understood. In part, this reflects imaging, near-infrared spectroscopy in hospitals than in the UK. This work others proposed that ‘hoarding disorder’ of a brain lesion.” These possibilities need to process: “If we ask them, when did this how difficult it is to study in early infancy, (NIRS), for use with infants. NIRS detects established that activity in social brain was a distinct clinical entity, a classification be excluded before a diagnosis of hoarding problem start, almost invariably they say says Mark Johnson an MRC scientist the same bloodflow signatures as fMRI areas fired up remarkably rapidly. “Only a now written into the psychiatrist’s disorder can be made. ‘in my childhood’. That’s why we started at Birkbeck, University of London: “The but, crucially, with more simple, cheaper few hours of social interaction is enough diagnostic bible, DSM-5, and also likely to As well as showing that hoarding disorder looking at childhood populations to try to surprising thing is, for the first year to and portable equipment. to get these cortical systems tuned up,” be included in the WHO’s ICD-11 guidelines. is distinct from OCD, and that the diagnostic understand the origins or seeds of what 18 months, it’s not been possible to Even so, developing detector caps for says Professor Johnson. Over the first few “It’s now globally recognised as a bona fide net does capture normal collecting behaviour, will later become problematic.” Indeed, use any behavioural markers to predict young infants was a technical challenge. days of life, social brain activity increased, separate entity,” says Dr Mataix-Cols. Dr Mataix-Cols has carried out population- a survey of adolescents found that autism at age 3; rather, they seem to Professor Elwell and Professor Johnson correlating with the levels of social stimuli He is keen to stress that the diagnosis based work to estimate its prevalence. Initial significant numbers, around 2 per cent, look fairly typical in terms of their overt worked side by side to develop the babies received. does not pathologise ‘normal’ behaviour, questionnaire-based surveys have suggested already reported problems discarding social behaviour. Looking at neural or brain technology and the scientific questions The combination of engineering such as collecting. “There might be some a prevalence of 2–5 per cent; more recent possessions. function measures is turning out to be it could address. The power of the new development and science underpinning Dr Mataix-Cols recently moved to more informative.” approach was confirmed in 2013, with NIRS has been highly productive, says the Karolinska Institute in Stockholm, To aid such work, Professor Johnson the striking discovery that, in response Professor Johnson: “We’ve been able to Sweden, and plans to continue working has established the British Autism Study to social stimuli, babies at risk of train up PhD and postdoctoral researchers on hoarding disorder. As well taking of Infant Siblings (BASIS), a national autism as young as 4–6 months showed who are experienced in both the infant advantage of the excellent twin registries network facilitating the study of infants abnormalities in the social brain areas of psychology, the neuroscience side, and in Sweden to study its epidemiology, he at risk of autism. Children with elder the temporal cortex known to be defective the medical physics side. It’s been very hopes to uncover more about its biological siblings with autism are themselves at in older children and adults with autism. successful.” The approach has now mechanisms, while better treatments for significantly greater risk of developing the At this stage, points out Professor been adopted by more than 20 groups patients are also an important priority: syndrome. Johnson, it is not possible to say whether worldwide: “It’s spreading fast so it shows “No one knows what to do with them; In 2012, Professor Johnson and these are early indicators of later autism, there’s a real need for it.” they’re very hard to treat.” colleagues used EEG and eye-tracking as the children have not yet reached the technology to show that abnormal age of clinical diagnosis. But if they are, Elsabbagh M et al. Infant neural sensitivity to dynamic eye Nordsletten AE et al. Epidemiology of hoarding disorder. Br J responses to social stimuli – faces – at NIRS may ultimately have value as a gaze is associated with later emerging autism. Curr Biol. Psychiatry. 2013;203:445–52. 2012;22(4):338–42. Ivanov VZ et al. Prevalence, comorbidity and heritability of around nine months of age was associated diagnostic tool (or at least a method to Lloyd-Fox S et al. Social perception in infancy: a near infrared hoarding symptoms in adolescence: a population based twin with diagnosis of autism at age 3. identify those at significant risk spectroscopy study. Child Dev. 2009;80(4):986–99. study in 15-year olds. PLoS One. 2013;8(7):e69140. However, although convenient, EEG has of autism). Lloyd-Fox S et al. Reduced neural sensitivity to social Nordsletten AE et al. Finders keepers: the features stimuli in infants at risk for autism. Proc Biol Sci. differentiating hoarding disorder from normative collecting. limited spatial resolution. For the past Not all infants at risk go on to 2013;280(1758):20123026. Compr Psychiatry. 2013;54(3):229–37. decade or so, Professor Johnson has been develop autism, however, suggesting Farroni T et al. Infant cortex responds to other humans from Mataix-Cols D et al. The London field trial for hoarding working with Clare Elwell in UCL’s Faculty that environmental inputs might be shortly after birth. Sci Rep. 2013;3:2851 The living space of a typical person with hoarding disorder. disorder. Psychol Med. 2013;43(4):837–47.

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olfactory cues is critical to food seeking. “So it’s The sweet smell of success important to understand how odour information is represented in the brain.” The first to develop ‘optogenetic’ approaches for neuroscience, Gero Miesenböck is Recent work has revealed how flies can now using the technology to probe the neural circuitry of fruit flies, particularly that discriminate between similar smells: “We found underlying olfactory-guided behaviour. there is a surprising mechanism where you have parallel excitatory and inhibitory lines innervating a brain region where odour discriminations are made. One of the most significant technological advances In January 2002, Professor Miesenböck Inhibition helps to separate overlapping odour Gero Miesenböck of the past decade, optogenetics allows for published a paper showing that the approach was representations.” extraordinarily precise manipulation of neural feasible, and sent Crick a preprint: “Once again he Optogenetics can make female flies sing like males. Interestingly, says Professor Miesenböck, this activity. Rather than just observe neural activity, replied quickly saying he was excited to see that idea is present in the artificial intelligence literature, neuroscientists can now intervene, assessing the system worked and that he looked forward to To show how optogenetics could be used, with suggestions that inhibitory signals can how stimulation (or inhibition) of specific neurons seeing how the field would develop.” Professor Miesenböck turned to sex. Fruit flies provide input gain control to enhance the ability of affects neural circuitry and the behaviour of living The impact of the 2002 paper took time to be display highly stereotyped sex-specific courtship ‘perceptrons’ to discriminate input patterns. “It was organisms. In a series of landmark publications, felt, says Professor Miesenböck. “I think it was a behaviours. The genetics of sex determination striking to find an implementation of this idea in Gero Miesenböck at the University of Oxford has slow burner. Several people have told me that when and control of sex-specific morphology were well the brain of the fly.” demonstrated the power of the new technology they saw it they ran to their supervisors and said established, but how nervous system function These studies, and the cellular engineering and how it can be applied to address critical ‘have you seen this?’ but overall it developed drove sex-specific behaviours was much less clear. underpinning optogenetics, emphasise a key biological questions. very slowly.” In 2005, it was discovered that the products theme of his research. “Engineering concepts and Optogenetic control grew out of studies using That all changed in 2005: “The second paper, of the fruitless gene, which come in male and physical principles should play a much larger role in genetic modification to visualise neural activity. in Cell in 2005, where we actually controlled the female forms, were critical controllers of sex- biology and neuroscience in particular,” he says. Hippocampal neurons were engineered to express behaviour of a fly, that started to stir people’s specific behaviour. But fruitless is active in just 2 “To approach biological systems with the mindset a protein that was stored in synaptic vesicles and imagination. It got a lot of attention, also in the lay “To approach per cent of neurons, and these 2000 or so neurons of an engineer can be very fruitful.” lit up after exocytosis. “That was the very first press – some of it quite crazy ‘mind control’ stuff. biological of male and female flies looked very similar. This theme permeates throughout the Centre genetically encoded reagent designed specifically But that paper showed what really might become systems with “Optogenetics was the obvious tool to get at that for Neural Circuits and Behaviour, established to look at activity in the nervous system,” recalls possible.” A significant boost, he adds, was the the mindset question,” says Professor Miesenböck. “It was a by Professor Miesenböck late in 2011 with Professor Miesenböck. In particular, it established subsequent adoption of channelrhodopsin, creating of an engineer wonderful opportunity to show off the power of funding from the Wellcome Trust and the the principle of using genetics to target and study a single-component and more efficient system: can be very the technique. It would have been unimaginable to Gatsby Charitable Foundation. Experimentalists, specific neural cell types. “That was a catalyst of the whole field taking off.” fruitful.” control a large and dispersed population of cells in engineers and theoreticians are using the fly Useful though this was, the extension to light an intact behaving animal with electrodes.” to understand how neurons act in concert to control of neural activity was a game-changer, Using optogenetics, he was able to switch on drive behaviour. Flies, he suggests, are an ideal and Professor Miesenböck can recall the precise the circuit dedicated to male-specific courtship in model, being easy to work with, cheap and with moment when inspiration struck: “It was the females, causing them to display male-specific powerful genetics, and none of the regulatory weekend, I’d taken a long walk and come back behaviours: “They started to sing as if they were overhead associated with vertebrates. “Although home and started reading a novel I was absorbed in trying to woo another female.” we sometimes joke that if our centre succeeds, at the time. Then suddenly I thought, wouldn’t it be The implication was that the adult fly brain is and we show how evolved the cognitive abilities amazing if one could use light to control a specific to a large degree built in a ‘unisex’ manner, with of fruit flies are, we might actually shoot ourselves genetically targeted cell type in the intact brain.” only a few master regulatory nodes flipping activity in the foot!” Unbeknownst to Professor Miesenböck, a between male and female behaviour. “Which I think Optogenetics remains core to the Centre’s work, similar thought had occurred to Francis Crick, who is a very economical and elegant solution to what’s though he is keen to stress that it is just a tool: had speculated about the possibility in a paper a very complex problem, namely how to build male “It is one method in an arsenal of many. We use it published in late 1999. “I became aware of that and female nervous systems. Wiring up a brain is when we can use it productively. I’m dismayed when article because he cites one of my earlier papers on probably the most difficult developmental problem I get applications from potential graduate students genetically encoded imaging probes, and I received evolution has had to solve, and if you had to find saying they would like to work on optogenetics. a citation alert via email. I read that paper and was two separate solutions for males and females I think they are putting the cart before the horse. stunned to see the importance Crick attached to that would complicate things further. If you build What always has to be the ultimate motivation is to the ‘far-fetched’ possibility of using light to control a unisex brain first, at a relatively late stage in solve a biological problem, not to apply a technique.” genetically targeted neurons, a possibility we were development you can just set a few switches and already working on it.” get male- or female-specific behaviour. I find that Zemelman BV et al. Selective photostimulation of genetically chARGed The connection led to a fruitful correspondence: quite appealing.” neurons. Neuron. 2002;33(1):15–22. Lima SQ, Miesenböck G. Remote control of behavior through genetically “I wrote to Crick to say we were doing these Professor Miesenböck went on to use targeted photostimulation of neurons. Cell. 2005;121(1):141–52. experiments and he sent back a very encouraging optogenetics to implant a new olfactory memory. Clyne JD, Miesenböck G. Sex-specific control and tuning of the pattern letter saying, ‘I’m surprised and delighted you’re “Olfaction has always played a significant role as generator for courtship song in Drosophila. Cell. 2008;133(2):354–63. Claridge-Chang A et al. Writing with light-addressable already doing this, please keep me posted about most of the behaviours we study are influenced by reinforcement circuitry. Cell. 2009;139(2):405–15. how your experiments progress’. Which is what odour inputs,” he points out. Pheromone detection Parnas M et al. Odor discrimination in Drosophila: from neural population I did.” The set up for implanting memories in flies. is important in sexual behaviour and memory for codes to behavior. Neuron. 2013;79(5):932–44.

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appear to have the same function in terms of Plasticity: from synapse to network synaptic plasticity. They have also suffered from a lack of pharmacological tools to isolate their While the molecular mechanisms of synaptic plasticity are gradually being unravelled, functions. So they tend to get a bit sidelined.” a further challenge will be to understand their effects on neural circuits. Nevertheless, he points out, because they appear to play a more modulatory role in synaptic and cellular function, they may prove better targets Synaptic plasticity has long been conceived as the With its well-established roles in memory to manipulate circuit behaviour. They are also highly neural basis of learning and memory. Ever since formation and spatial navigation, and well- conserved and have recently been linked genetically Jack Mellor the first demonstrations of long-term potentiation described neural architecture, the hippocampus is to several human diseases: “So they must be really (LTP) more than 40 years ago, researchers have an excellent model in which to address these kinds important for something.” searched for the cellular mechanisms that cause of question. “What we’ve become interested in is As well as showing how they can influence the properties of a neuron to change following how the hippocampus actually encodes memories,” the excitability of pyramidal cells, Dr Mellor stimulation. Jack Mellor at the University of he says. In the context of spatial memory, that has become increasingly interested in their Bristol, recent recipient of a Wellcome Trust New means understanding the coordination of ‘place developmental role. They appear to play a Investigator Award, has spent much of his career cells’ – hippocampal cells that fire when an significant part in wiring up the developing exploring these mechanisms of synaptic plasticity. animal is in a specific spatial location. It is has “If we can nervous system, particularly the hippocampus. Now, though, he is shifting his focus to understand been suggested that synaptic plasticity could understand Abnormalities in this development could how they influence neural circuits responsible for arise if place cells responsive to similar locations how have long-term consequences: “If you have key neurobehavioural phenomena such as memory. were synaptically connected (and, indeed, that acetylcholine disruptions to the wiring up of neuronal networks After a PhD at the MRC Laboratory of the degree of plasticity would reflect how close has its effects... Visualisation of kainate receptors in hippocampal neurons. in development, that is likely to be important Molecular Biology in Cambridge with Andy Randall, locations were, providing a way to encode then we would in certain neurodevelopment disorders. We Dr Mellor’s first postdoctoral appointment enabled spatial distances). hope to be able selective approaches. Dr Mellor has established think kainate receptors and the control of their him to spend two years in the USA – working With John Isaac, Dr Mellor was able to show that to say this is collaborations with industrial partners, Lilly and functional expression may be important for this.” with Roger Nicoll at the University of California this did indeed happen. By transposing place cell the target you GSK, and hopes his work will have practical spin- With Jeremy Henley, Dr Mellor has also been San Francisco – and a final year in John Isaac’s activity from freely moving rats into hippocampal ought to offs: “If we can understand how acetylcholine has examining the cell biological mechanisms that lab at Bristol. After an MRC Career Development slices, he was able to show that LTP could be induced go for.” its effects, which specific receptors it targets to control trafficking of kainate receptors to and from Fellowship, he secured a permanent academic but only when place cells had coincident firing fields. improve the function of that hippocampal network, the neuron cell surface. This work has identified position at Bristol. “We’re now moving on to think about how that then we would hope to be able to say this is the a key role for phosphorylation and addition of the “My background is as a synaptic physiologist,” plasticity might enable place cells to be wired up to target you ought to go for.” ubiquitin-like ‘SUMO’ polypeptide, SUMOylation, in he explains. “Right now we study hippocampal maintain or encode an engram or memory from that A key question, he suggests, will be the intracellular trafficking. A further collaboration with networks and and how they function.” group of cells within the hippocampal network.” nature of acetylcholine receptors expressed on Jonathan Hanley is examining intracellular proteins And although synaptic plasticity lies at the heart of hippocampal cells. He and others have begun regulating AMPA receptor trafficking during his work, he is now looking at wider issues: “We’ve Acetylcholine: the key to memory? to identify routes through which activation of synaptic plasticity and under ischaemic conditions moved towards also thinking about what plasticity Notably, induction of LTP in place cells was dependent different receptor subtypes can influence plasticity. where changes to AMPA receptor expression means to the function of the network.” on raised levels of acetylcholine. This neuromodulator A major challenge now is to integrate these influence excitotoxicity. Such studies will continue has a critical role in hippocampal function, and is an disparate findings: “Quite a lot of work has already to provide molecular insight into how the properties area of growing interest in Dr Mellor’s lab. been done on which receptors are expressed on of individual neurons and synapses are controlled. This strand of work has important translational which cell types and what the functional effects of An additional challenge will then be to integrate implications, particularly for the development those receptors are. What were trying to do is put this knowledge to understand how networks of of cognitive enhancers to treat memory deficits. that together into an integrated network model.” neurons can work together to achieve the mysteries Acetylcholine levels fall during early stages of Hence, the lab has a growing interest in of memory and learning. Alzheimer’s disease, and components of the computational models: “We’ve been developing our acetylcholine system have been widely targeted approach to computational modelling for a while Isaac JT, Buchanan KA, Muller RU, Mellor JR. Hippocampal place cell as a strategy for boosting or maintaining memory: and we’re at the stage where we have some really firing patterns can induce long-term synaptic plasticity in vitro. J Neurosci. 2009;29(21):6840–50. “The only treatments we currently use for the good models being built at the moment, and the Buchanan KA et al. Facilitation of long-term potentiation by muscarinic cognitive deficits in Alzheimer’s disease are predictions they make can be really exciting.” M(1) receptors is mediated by inhibition of SK channels. Neuron. the cholinesterase inhibitors, and no one really 2010;68(5):948–63. Chamberlain SE et al. Long-term depression of synaptic kainate knows how or why they work,” Dr Mellor points Standing up for kainate receptors reduces excitability by relieving inhibition of the slow out. “There’s an idea they boost the amount of Another strand of Dr Mellor’s research focuses afterhyperpolarization. J Neurosci. 2013;33(22):9536–45. acetylcholine in the cortex and the hippocampus. on kainate receptors which, he argues, have been Chamberlain SE et al. SUMOylation and phosphorylation of GluK2 If that is the case, we might want to understand unjustly neglected: “They’re always seen as the regulate kainate receptor trafficking and synaptic plasticity. Nat Neurosci. 2012;15(6):845–52. more about what acetylcholine is doing to those poor cousins of the other more famous ionotropic Dennis SH et al. Oxygen/glucose deprivation induces a reduction in networks to cause those effects.” glutamate receptors, AMPA and NMDA receptors. synaptic AMPA receptors on hippocampal CA3 neurons mediated by Moreover, current treatments are not very There is a perception they do the same thing as mGluR1 and adenosine A3 receptors. J Neurosci. 2011;31(33):11941–52. Theta rhythms in the hippocampus provide a mechanism for encoding of spatial trajectories in the hippocampus. Sadowski JH, Jones MW, Mellor JR. Ripples make waves: binding From Sadowski et al. effective and have significant side-effects, so there AMPA receptors but weaker and they’re not nearly structured activity and plasticity in hippocampal networks. Neural Plast. is significant potential to develop better, more as exciting as NMDA receptors, because they don’t 2011;2011:960389.

22 BNA Bulletin Spring 2014 www.bna.org.uk www.bna.org.uk Spring 2014 BNA Bulletin 23 Research Research

spinal injury – dopamine. During development, The remarkable regenerating fish growth of brainstem neurons needs to be integrated with the generation of motor neurons Zebrafish can rapidly repair a severed spinal cord. A better understanding of how along the body axis. Descending axons of they do so may suggest ways to enhance human nerve regeneration. dopaminergic neurons in the brain play this key role during development, and also during regeneration. Acting through the dopamine D4a receptor and Catherina Becker, based at the Centre for regeneration in collaboration with her husband and the hedgehog pathway, brainstem dopaminergic Neuroregeneration in Edinburgh, has long been co-investigator Thomas Becker. In mammals, spinal neurons promote motor neuron development at Catherina Becker fascinated by the ability of amphibians to regrow cords are essentially unable to regenerate, but the expense of interneurons. body parts. For the past 20 years, however, it is a paralysed fish with a severed spinal cord the zebrafish, a more convenient experimental will typically recover within six weeks: “Most of Regeneration and neurodegeneration model, that has been her main focus. It too shows them will swim as if nothing has happened,” Such studies have drawn attention to the Zebrafish, a valuable model for regeneration research. remarkable powers of recovery, and Professor says Professor Becker. importance of factors such as Notch, hedgehog Becker’s group has begun to identify the molecular “That obviously is a very interesting signalling and dopamine in nerve regeneration. But mechanisms underpinning this regenerative capacity. phenomenon,” notes Professor Becker. “You’re fish are also providing insight into a related area, “Frogs and salamanders, especially taking an adult nervous system and damaging it, neurodegeneration. salamanders, are fantastic regenerators, but rather and the anatomical recovery is not 100 per cent but Oddly, the relevance of zebrafish to iffy to keep in the lab,” says Professor Becker. the functional recovery is.” Furthermore, zebrafish neurodegeneration featured in the recent Spider- “As zoologists, you can do fantastic things like are easy to grow and to manipulate genetically, man reboot, The Amazing Spider-Man. Dr Curtis breed them out of season by putting them into and are amenable to all kinds of studies from the Connors, aka the Lizard, is missing a right arm the vegetable compartment of your own fridge cellular and molecular through to the behavioural: and keen to translate experimental work on limb to mimic winter.” Her mother was not so keen “That’s what’s really neat about the fish. It offers “That’s what’s regeneration. On a school trip to his lab, Spider- on her bringing work home, and amphibians also us this whole spectrum of approaches.” really neat Man’s alter ego, Peter Parker, highlights the direction have experimental drawbacks: “They do not lend about the fish. Connors is taking: “A person gets Parkinson’s themselves well to, say, genetic or high-throughput Development and regeneration It offers us when the brain cells that produce dopamine start studies. Each individual is quite precious as you’ve One key theme of Professor Becker’s work is the this whole to disappear. But the zebrafish has the ability to bred them yourself and raised them to adulthood, seemingly close connection between development spectrum of regenerate cells on command. If you can somehow which takes over a year.” and regeneration. Many of the processes that build approaches.” give this ability to the woman you’re talking about, So, on moving to the Swiss Federal Institute a fish in the first place are also used in repair after that’s that. She’s…she’s curing herself.” of Technology in 1994, Professor Becker turned injury. Hence insight into developmental processes A screen for genes involved in motor neuron to zebrafish, establishing a model for spinal cord may also provide clues to regeneration. differentiation triggered Professor Becker’s interest Newly born motor neurons (red) in a cross section of the adult zebrafish Her main interest has been regrowth of motor in a lectin-like protein, chondrolectin. Coincidentally, spinal cord, some labelled with BrdU (blue); spinal progenitor cells and neurons, spinal neurons driving the muscular Kevin Talbot in Oxford and others implicated oligodendrocytes (green). contraction required for swimming. In 2008, now in chondrolectin in the death of motor neurons in spinal Edinburgh, she showed that, after spinal cord lesion, muscular atrophy (SMA), a form of motor neuron powers of regeneration. “It’s very hard to imagine progenitor cells in the spinal cord switch from making disease. In fish, chondrolectin seems to have a role an evolutionary advantage,” says Professor Becker. glia to motor neurons. These new cells integrate into in axon pathfinding, but collaborative work with In the wild, an animal with a severed spinal cord existing circuitry, underpinning regain of function. Professor Talbot suggests it may also be involved in is unlikely to survive the six weeks required to In terms of mechanisms, a key role is played by cell survival. Notably, boosting chondrolectin levels regain swimming abilities. Perhaps, she suggests, the developmental morphogen sonic hedgehog. rescued the SMA phenotype in zebrafish. the mechanisms help to repair minor damage Hence, the adult fish nervous system appears to Professor Becker, Professor Talbot and Professor incurred during daily life. Whatever the explanation, maintain a class of progenitors, or stem cell-like Tom Gillingwater in Edinburgh are continuing to understanding how zebrafish achieve what cells, capable of being activated by sonic hedgehog explore the cellular and developmental phenotype mammals cannot may ultimately point the way and generating new motor neurons. of chondrolectin-deficient fish. In addition, a drug to much-needed therapies. One suggested reason for the lack of spinal cord screen is being undertaken to identify compounds regeneration in mammals is high levels of Notch able to rescue the motor neuron deficits and Reimer MM et al. Motor neuron regeneration in adult zebrafish. J Neurosci. signalling – Notch is thought to play a key role in generate potential therapeutic leads. 2008;28(34):8510–6. Reimer MM et al. Sonic hedgehog is a polarized signal for motor neuron cellular decision-making between proliferation and In other studies, zebrafish will be used to regeneration in adult zebrafish. J Neurosci. 2009;29(48):15073–82. differentiation. Notch signalling is also enhanced assess the neuroprotective effects of compounds Dias TB et al. Notch signaling controls generation of motor neurons in after spinal cord lesion in zebrafish, but apparently developed by a local biotech firm, Antoxis. the lesioned spinal cord of adult zebrafish. J Neurosci. 2012;32(9): 3245–52. not to levels that shut off new neuron production Complementing work on human patient-derived Reimer MM et al. Dopamine from the brain promotes spinal motor completely. Hence regeneration may depend on cells (led by Tilo Kunath), the work on fish will reveal neuron generation during development and adult regeneration. Dev Cell. Notch levels being neither too high nor too low – or whether the compounds actually have a protective 2013;25(5):478–91. in the ‘Goldilocks zone’ as Professor Becker puts it. effect on motor neuron function. Sleigh JN et al. Chondrolectin affects cell survival and neuronal outgrowth Motor neuron (green) newly born 2 weeks after injury of the adult in in vitro and in vivo models of spinal muscular atrophy. Hum Mol Genet. zebrafish spinal cord, not yet decorated by synapses (red). Recently, Professor Becker and colleagues have Returning to the original biological 2014;23(4):855–69. identified a key factor driving regeneration after phenomenon, it remains unclear why fish have such

24 BNA Bulletin Spring 2014 www.bna.org.uk www.bna.org.uk Spring 2014 BNA Bulletin 25 Research Research Networking opportunities Studies of the brain’s folding patterns, and other forms of structural and functional brain imaging, are providing new insight into schizophrenia – and suggesting possible new strategies for intervention.

It has long been hoped that brain imaging will have argued that it is a neurodegenerative condition. Lena Palaniyappan ultimately impact on psychiatric practice. According “So looking at folding patterns gave an idea that to Lena Palaniyappan, an academic psychiatrist maybe a significant proportion of what we see in grey at the University of Nottingham, that day is fast matter is not simply a result of degeneration – a lot approaching, with brain imaging moving from a of it has probably happened very early in life, even descriptive to a mechanistic understanding of before the age of two.” mental disorders. The implications of these findings are significant. After his medical degree in India, Dr They suggest good places to start looking to Palaniyappan undertook postgraduate medical understand mechanisms of disease. And if cell death Graphs based on volumetric patterns in schizophrenia. The nodes indicate specific brain regions while edges indicate the relationship between two regions. training in Nottingham and Newcastle. He is is not the cause, there may be more potential to now a Wellcome Trust Clinical Research Fellow in exploit the brain’s innate plasticity in treatment. His focus was drawn to the insula, one of Furthermore, they point to a specific pathway Translational Neuroimaging in Psychiatry, and is Dr Palaniyappan has gone on to show that the most highly folded parts of the brain and that could be targeted in treatment. Several interested in the use of brain imaging – structural gyrification abnormalities appear to have biological one showing significant folding abnormalities in possible approaches could be envisaged to boost and functional – to understand conditions such as significance. Notably, with Paola Dazzan and Robin schizophrenia. “So we thought, let’s look at how activation of the salience network, including schizophrenia. Murray at King’s College London, he has discovered this region is connected to the rest of the brain – neurofeedback (‘brain training’), neurostimulation “One of the most robust findings in imaging is a correlation with treatment response – those with let’s see if it’s different in people with schizophrenia (transcranial magnetic stimulation or transcranial loss of grey matter in patients with schizophrenia,” the most striking gyrification abnormalities showed compared to healthy controls.” direct current stimulation), pharmacological he points out. “My question was, is this just simple poorest responses to anti-psychotic treatments. In This time he turned to functional imaging, interventions or through cognitive approaches loss of grey matter? Do people lose chunks of grey addition, in patients suffering a psychotic episode, applying Granger causal modelling techniques to such as mindfulness – or, indeed, a combination matter tissue, or is anything else happening on the abnormal gyrification was greater in schizophrenia understand functional connectivity between areas of methods. surface of the brain? For example, is it thickness than bipolar disorder patients. This makes sense, of brain activity. The key test was to examine Dr Palaniyappan is currently involved in a trial that is lost or the folding pattern of the brain, or is he suggests, as bipolar disorder is not thought to activity while the brain was in ‘idling mode’ – when using magnetic stimulation on normal volunteers: it the surface area that is shrinking? What exactly be a neurodevelopmental condition. the distinctive ‘default mode network’ is typically “If we find signals strong enough to suggest that is happening?” Hence, brain imaging could help to characterise “... all sorts of active. When the brain needs to attend to an insula can be modulated by focused magnetic Conventional morphometric structural imaging patients early in disease. Illness trajectories and changes were external stimulus, the default mode network shuts stimulation of frontal cortex, we will then try this techniques provide insight into volumes but little treatment response profiles are remarkably happening in down and activity boots up in a ‘central executive on a clinical population, patients with psychosis or else. Instead, Dr Palaniyappan turned to surface- heterogeneous in psychotic disorders. With novel the brain in network’ embedded in the prefrontal cortex. These depression.” Other studies are aiming to get at the based morphometry, which takes 3D brain images imaging approaches, it may therefore be possible to schizophrenia, transitions are triggered by a ‘salience network’ neurochemical basis of defective network activity, and converts them into a two-dimensional sheet of provide some guidance to patients on the likely course but the most centred on the insula, a brain mechanism thought and the possible involvement of glutamate and cortex, allowing features such as thickness, surface of their disease, and also to give clinicians some clues striking was to be responsible for switching between internally GABA signalling. area and brain folds to be examined. “When we to the likely response to treatment in psychosis. the reduction and externally focused attention. Dr Palaniyappan’s work forms part of a wider looked at it, all sorts of changes were happening in in the Dr Palaniyappan and colleagues discovered a Centre for Translational Neuroimaging in Mental the brain in schizophrenia, but the most striking was Making connections complexity striking reduction in salience network connectivity Health at Nottingham, led by Peter Liddle. Brain the reduction in the complexity of the brain folds.” A key question remains – what is the cause of of the brain to the executive network in people with imaging is non-invasive, quick and feasible even for The brain’s primary folds (gyri) and furrows (sulci) the gyrification abnormalities in schizophrenia? folds.” schizophrenia. “And, interestingly, the amount of acutely affected patients. It is, he suggests, close to are common to all, and form the basis of standard Although he stresses it is speculative, Dr reduction directly predicted how unwell the patients giving clinicians useful information about individual brain atlases. However, smaller-scale secondary sulci Palaniyappan points to animal studies showing were. The clinical severity and the functional ability patients. In the meantime, it is also generating show more variability. Notably, the brains of people that early damage to white matter pathways in of the patients were very much related to the vital information about the mechanisms underlying with schizophrenia showed distinctive gyrification rodents leads to altered gyrification in adults. “This reduction in connectivity between the insula and these devastatingly complex conditions. abnormalities, mostly reduced complexity of folding. is maybe what is happening in schizophrenia, even the frontal cortex.” “This is important, as many of the folds we have in before the age of two. Possibly there are some These findings, he suggests, make sense of the Palaniyappan L, Liddle PF. Aberrant cortical gyrification in the brain, the gyrifications, these are decided very lesions in the white matter tracts which are not diverse and puzzling symptoms of schizophrenia: schizophrenia: a surface-based morphometry study. J Psychiatry Neurosci. 2012;37(6):399–406. early in life. By around two years of development, immediately visible but in adult life they produce “The clinical features of schizophrenia are very Palaniyappan L et al. Cortical folding defects as markers of poor most gyrification is complete.” this disturbed folding patterns.” diverse and don’t immediately appear to be treatment response in first-episode psychosis. JAMA Psychiatry. The findings thus point to an early origin for these This way of thinking emphasises the importance connected with each other. But you can explain a 2013;70(10):1031–40. Palaniyappan L, Liddle PF. Diagnostic discontinuity in psychosis: a brain abnormalities in patients. “Although the story of of neural circuitry in schizophrenia – and here Dr lot of them using this simple model, that there is combined study of cortical gyrification and functional connectivity. schizophrenia being a neurodevelopmental disorder Palaniyappan has uncovered tantalising evidence a switch in the insula and that this switch doesn’t Schizophr Bull. 2013. [Epub ahead of print] has been bubbling for a while, there’s no convincing of a possible mechanistic basis for the diverse and function effectively – people don’t switch between Palaniyappan L et al. Neural primacy of the salience processing system in proof,” notes Dr Palaniyappan. To his concern, some troubling symptoms of the disease. the internal and external world effectively.” schizophrenia. Neuron. 2013;79(4):814–28.

26 BNA Bulletin Spring 2014 www.bna.org.uk www.bna.org.uk Spring 2014 BNA Bulletin 27 Et cetera Et cetera The legend of the Black Horse (revisited)

Robert Balazs and Edward H Reynolds Reply from Joelle M Abi-Rached, Steven Rose and John Lagnado

Within 50 years, the BNA has grown from a few dozen scientists to a large and Balázs and Reynolds’ wish to honour Derek Richter is understandable on several levels, flourishing organisation. It is timely to recall the foundation of the Brain Research including personal ones (Richter found a job for Balázs when he left Hungary after the Association (BRA), which later became the BNA, especially as a legend has arisen that abortive revolution of 1956), but in this context unsustainable. Two of us were original the BRA was founded in 1968 by a group of London-based neuroscientists meeting members of the Black Horse group. A third, the late Herman Bachelard, wrote an account informally in a pub, the Black Horse, between 1965 and 1968 (Refs 1–3). This legend is of those early days in the BNA Bulletin: factually incorrect and we wish to set the record straight based on documented evidence “[...] in researching this short history, two of the founders (John Lagnado and and our own experience (Ref. 4). One of us (R.B.) was one of the four founding members Steven Rose) both confirmed that Derek Richter had not been a founding member as of the Black Horse group. he had suggested in his memoirs (Life in Research, Stuart Philips, 1989). What actually Derek Richter (1907–1995) was Director of the multidisciplinary MRC happened was that, a year or so after the beginnings of the Black Horse Group, Derek Neuropsychiatry Research Unit from 1955 until his retirement in 1971. Among several Richter (towards the end of 1968), as a UK representative of the International Brain international contributions to neuroscience, he was a founder member and served on Research Organisation (IBRO), suggested that it become affiliated with IBRO as the the first Council of the International Brain Research Organisation (IBRO) in 1960. In that Brain Research Association (BRA). This was agreed and the group then broadened to capacity he and fellow Council member Donald MacKay first wrote to 29 neuroscientists include neuroscientists from outside London, and an informal organising committee… throughout the UK on 6 July 1967 enquiring about the possibility of establishing a was established…” (Ref. 5). national BRA, such as then existed in the USA, USSR and Japan. Only five respondents In her account, Abi-Rached (Ref. 2) argued that the BNA – and hence its predecessor, opposed the idea. the BRA – could be viewed as a “more formal prolongation of the Black Horse meetings”, Richter convened and chaired a meeting at the National Hospital, Queen Square, emphasising the vital role played by other like-minded scientists who, beginning in London, on 23 February 1968, which unanimously agreed to establish the BRA and elect the 1960s started to think about the brain in interdisciplinary ways. Neuroscience an Organising Committee (OC). Richter conducted a postal ballot and eight members was in the air. The term appeared in 1963 in the title of the official bulletin of a new of the OC were elected from different neuroscientific disciplines according to IBRO initiative, the Research Program (NRP), founded a year earlier by MIT principles. The OC first met on 9 May 1968 and invited Richter to attend. Richter outlined biophysicist Francis O Schmitt. Rose was one of the only four British scientists among how the BRA had been formed and the Committee elected. The Committee thanked 136 participants at the NRP’s first ‘Intensive Summer Program’ in 1966 in Colorado. It Richter for the major part he had played in founding the BRA. At the first AGM of the was this and earlier NRP activities that inspired him to bring together the group that BRA on 7 May 1971, when the Constitution was approved, Richter proposed the vote of initiated the Black Horse meetings in 1965. thanks to the Officers. The role of the diverse and enthusiastic group of scientists who initially met at The above are the documented facts. But in their account, Abi-Rached and Rose the Black Horse (many of whom became, and remain, BNA members) should not be have written Richter out of the story. Instead they claim incorrectly that the BRA trivialised. Five of the eight members of the first BRA committee were from the Black started as a group of like-minded scientists who met at the Black Horse and “from Horse group (Rose chose not to stand due to pressure of other commitments). John the London discussion group we became the BRA”. The Black Horse group was set Dobbing and Chris Evans were elected joint secretaries, and Pat Wall was the BRA’s first up in 1965 by four neuroscientists including Rose and one of us (R.B.) to promote chair. In addition, not only was the London group the backbone of the BRA, it was its discussions and exchange of ideas between London-based neuroscientists in a friendly engine and a model to emulate. The minutes of the first meeting of the BRA (9 May and congenial environment. The meetings were informal and academic. There were 1968) state: “This informal group with approximately 200 members might well form the no minutes and there was no political agenda. The group did not, as Abi-Rached and nucleus of the London branch of the new Association” (Ref. 6). The second meeting (19 Rose claim, organise conferences, workshops or courses. The latter activities were all September 1968) describes the increasingly growing informal network of the Black Horse begun by the newly formed BRA, as the minutes confirm. This does not diminish the group as the model for other burgeoning groups of the BRA. Hence Bachelard is correct contribution of the members of the Black Horse group to the subsequent work of to state that: “The London group remained the most active with regular meetings the BRA. taking place either at the pub or, increasingly, at Queen Square” (Ref. 5). 1. Abi-Rached JM, Cooke A, Rose S. The legend of the Black The legend of the Black Horse appears to be based on frail memories, inadequate To reiterate arguments already mentioned in letters exchanged in the Journal of the Horse. BNA Bulletin 2011;63: 20–1. 2. Abi-Rached JM. From brain to neuro: The Brain Research historical research and perhaps some degree of wishful thinking. Rose, who was not History of the Neurosciences (Refs 2–4), Richter certainly helped expand the Black Horse Association and the making of British neuroscience, elected to the OC of the BRA, but was later co-opted, was not one of the founders of group into a formal organisation that could represent UK interests on the IBRO but his 1965–1996. J Hist Neurosci. 2012;21:189–213. the BNA as stated in the BNA Bulletin, but he was a founding father of the Black Horse role was ‘catalytic’ rather than foundational. To describe him as the ‘founding father’ of 3. Abi-Rached JM, Rose SPR. Of founding fathers and history. J Hist Neurosci. 2013;22: 208–11; 215. group. Richter, who was a member of both the Black Horse group and the BRA, was the the BNA is another legend that needs to be deconstructed, if not for the appreciation 4. Balazs R, Reynolds EH. Derek Richter, the British Brain major founder of the BRA and thus the BNA. of the many scientists who took part in the making of neuroscience in the UK (Balázs Research Association, and the Legend of the Black Horse. J included), then for history’s sake. Hist Neurosci. 2013;22:199–207; 212–4. 5. Bachelard HS. A Brief History of the British Neuroscience Robert Balazs is an Honorary Senior Research Associate, UCL; Edward H Reynolds is a Consultant Neurologist and Honorary Association 1967–1993. BNA Bulletin. 2004;48:10–1;30. Senior Lecturer, King’s College London. Joelle M Abi-Rached is MD, MSc, PhD candidate in History of Science at Harvard University; Steven Rose is Emeritus 6. SA/BRA/A (Executive) committee minutes, 1968–1987; Professor of Biology at the Open University and Emeritus Professor of Physick at Gresham College London; John Lagnado is Archives and Manuscripts Collection, the Wellcome Library, The original BNA Bulletin article. Honorary Archivist, the Biochemical Society (UK). London, UK.

28 BNA Bulletin Spring 2014 www.bna.org.uk www.bna.org.uk Spring 2014 BNA Bulletin 29 Et cetera Et cetera

have I done now?’” In fact, the letter bringing together work on stem cells and was an enquiry to see if she would be regenerative medicine as well as pain and interested in accepting the honour, should sensory disorders. it be offered. Interestingly, she also took time out She answered in the affirmative, and from Merck to work for the Independent in December 2013 made the trip to SW1A: as a science writer, winning an award for “Having my husband drive through the best series of articles in a broadsheet Guang-Zhong Yang, Lady Gwen Borysiewicz, Barbara J gates of Buckingham Palace with my kids in newspaper. “After that, I wrote a book, Sahakian and Sir . the car was exciting,” she recalls. Colleagues Billy’s Halo, which was shortlisted for the were similarly swept along: “People at work MIND book of the year (it didn’t win but were very excited for me and had a necklace it was nice to go the party).” The book is the effects of poverty on the brain in made, which they commissioned, with an unusual mix of science and personal children and healthy ageing. neurons on the front of it.” reflection, centred on her father, Billy, Important sessions covered how we The day itself provided an a life-threatening bout of septicaemia might, through new developments and opportunity to meet high achievers and his eventual death. Still keen on technology, promote new discoveries from all walks of life. communication, time pressures are that could impact on both mental health currently inhibiting further forays into and wealth development. For example, “I sat next to Bradley print: “I have an idea for another book, much new technology, including optical Wiggins so had a nice which might get written when I retire.” Every year, world notables gather at Davos. imaging and computing, is being invented chat to him. It was quite Now, the challenges of developing new for the Human Brain Projects, discussed interesting because he medicines for pain and other conditions, by Allan Jones (Allen Institute, Seattle), seemed to think he’d done as well as a multitude of other work, Thomas Insel (National Institute of Mental nothing special and I had. such as helping to establish a Catapult Davos in mind Health, Bethesda) and Henry Markram And I was thinking, ‘yeah Centre to support the development of (Lausanne). Much of this will be applicable but Bradley, I can’t even cell therapies, and sitting on various At the recent World Economic Forum in Davos, Barbara J Sahakian in businesses, including those using large ride a bike…” high-level boards, more than fill her time. had an opportunity to convince world leaders of the importance of databases, and biotech companies. She is excited by the potential of stem neuroscience to global wellbeing, brain health and wealth. In addition, in one of my own sessions, Indeed, she ended up rubbing cells, both as therapies but also as tools facilitated by Nature Editor Philip Campbell shoulders with all kinds of high achievers: to understand disease processes and and introduced by surgeon Lord Darzi, “It was interesting to talk to people from the effects of drugs. She also believes Amongst the thrill of seeing many heads stop these debilitating disorders from there was extensive discussion of robotics Ruth McKernan CBE. all different walks of life, where their that genetics and intensive phenotyping, of states and the glitz associated with becoming chronic and lifelong. Enhancing and games for cognitive training. And the colleagues and peers think of them as the as well as electronic health record and Davos was the excitement of realising cognition through pharmacological and potential for theory of mind in robots was best in their discipline. It was an honour, epidemiological data, are generating that governments around the world have other means, including good nutrition, discussed in the session moderated by A day at and I was and still am very excited by it.” exciting opportunities for more targeted finally got it! They finally understand that exercise, education and ‘serious games’, Lord Rees, former President of the Royal From a scientific family – her father, ‘precision medicine’. there is no greater financial or societal will be essential. Society. All these sessions generated Billy, was a biochemist – Dr McKernan While some pharmaceutical companies challenge than the impact of mental It is encouraging that governments much lively discussion with the audience – the Palace studied pharmacology and biochemistry have withdrawn from CNS conditions, Dr health disorders. realise that they need to promote good mainly business leaders, government at King’s College London before a PhD at McKernan believes the great strides being Dementia, depression and other brain health across the lifespan. This officials and the media. the Institute of Psychiatry, looking at the made in understanding such conditions neuropsychiatric disorders destroy mental will create resilience in individuals and a Both science and technology and Ruth McKernan’s career has mechanism of action of antidepressant will eventually tempt industry back. “I see capital and wellbeing. One in four of us flourishing society. Since 75 per cent of higher levels of cognitive abilities taken her to San Diego and to drugs. After postdoctoral work at the that as a temporary lull. Where science will suffer from a mental health disorder mental illnesses start before the age of 24 and education are linked to increased senior positions in some of the University of California San Diego, she leads pharma companies will follow.” at some point in our lives. Alzheimer’s years, it is important that we detect and prosperity (e.g. increased gross domestic world’s biggest pharmaceutical returned to the UK to join Merck. She finds refuge from helter-skelter disease, schizophrenia, depression and treat them in young people. product). Furthermore, investment in companies – as well as to a seat “I’d always been interested in daily pressures in the garden. Here, she mania all have associated cognitive Governments need to consider mental health has provided substantial next to Sir Bradley Wiggins at medicines, and how to make medicines, suggests, the tranquility provides scope symptoms. It is these problems with mental health as every bit as important economic benefit in the past, and should Buckingham Palace. particularly in psychiatric and CNS to make sense of the weekly information attention, memory, decision-making, as physical health. A commitment to continue to do so in the future. disorders,” she explains. “There’s a huge overload: “Sometimes you just need that planning, problem-solving and impulse neuroscience and mental health will Let’s hope that Davos has even greater In 2013, Ruth McKernan, chief scientific gap in how people are treated. I’m sure quiet time to reassimilate and reprioritise. control that compromise our ability to ensure good mental capital and wellbeing contributions from neuroscience and officer of Neusentis, a unit within Pfizer, there are much better drugs to be made.” I find it very therapeutic.” work and create difficulties in activities for all members of society. It is a win– mental health in 2015. was awarded a CBE in The Queen’s She spent 17 years at Merck, rising of daily living. Absenteeism and win situation, since new discoveries and Birthday Honours. The award recognised from junior scientist to head of site, and A short piece Ruth McKernan wrote for the Guardian ‘presenteeism’ at work for those with treatments will generate new businesses Barbara J Sahakian is Professor of Clinical Neuropsychology her work in business and innovation. establishing her reputation with work on reflecting on her father’s illness and eventual death can be depression, and institutional care for those and aid the economy, while also reducing at the Department of Psychiatry and MRC/Wellcome Trust found at bit.ly/1gDtkUH Behavioural and Clinical Neuroscience Institute, University The CBE came out of the blue: “I was subtype-specific drugs for GABA receptors. with dementia, constitute major financial healthcare costs and burden to society. of Cambridge. She is also the author (with Jamie Nicole at work and my husband called me and From Merck in Harlow, she transferred to problems for global productivity. At Davos, there was much neuroscience LaBuzetta) of Bad Moves: How decision making goes said ‘there’s a letter here from the Cabinet Pfizer in Sandwich, before the company’s Neuropsychiatric disorders often discussion that ranged from very basic wrong, and the ethics of smart drugs (Oxford University Office, do you want me to open it?’ My reorganisation in 2011 enabled her to go undetected and untreated, so early science, such as the Human Brain Projects, Press, 2013). immediate thought was, ‘Oh God what establish the Neusentis unit in Cambridge, detection and treatment are key. We can both US and European, to understanding

30 BNA Bulletin Spring 2014 www.bna.org.uk www.bna.org.uk Spring 2014 BNA Bulletin 31 Et cetera Et cetera

Q&A: Rumana Chowdhury process. My research used a variety of Q: What are your long-term plans? Obituary It is with profound sadness to reflect on the loss projects with scientists and clinicians at the I-NK techniques to examine how this loss of A/ I plan to pursue a career as an of Professor Colin Ingram. Colin was a scholar, a Institute of Neuroscience in Kolkata, India. I regret dopamine might affect human cognition academic neurologist, dividing my time genteel man, a teacher and a friend. He passed I missed this exciting venture because of my own in older age. I found that reinforcement between research and clinical work. In away unexpectedly at home in Newcastle on 15 outreach obligations in Nigeria and Rwanda. Colin learning and episodic memory could be my future research, I intend to examine December 2013. achieved all these prodigious successes through improved by giving older adults a drug to neural networks underlying cognition An accomplished neuroscientist, Colin was the his resilience and convivial personality, persuading increase dopamine levels. I used MRI to and how these networks break down founding Director of the Institute of Neuroscience people to work together and always looking for the show that these effects were related to in ageing and neurological disorders (IoN) at Newcastle University. Colin came to best in colleagues around him. the structural integrity of the dopamine such as Alzheimer’s disease. I hope that Newcastle from the University of Bristol in July I believe the BNA owes him particular system and functional activation in this line of work will provide a deeper 2000, appointed to the Chair in Psychobiology thanks. Colin played a significant part in the dopamine target regions including the understanding of cognitive dysfunction in the School of Neurology, Neurobiology and BNA for over a decade: he was first elected to nucleus accumbens and hippocampus. and provide a basis for developing Psychiatry. He subsequently served as Head of the national committee in 2001, subsequently The importance of this work is that it therapies for people with memory Colin Ingram the School (2006–08), which transformed into served as Treasurer (2004–07) and finally as brings together the biological, structural problems. (1960–2013) the IoN in 2008. Until his death, he shared this Honorary Secretary (2007–11). While I had the and functional changes in the ageing Q: What advice would you give to a role on a rotating basis with Anya Hurlbert. He privilege to work with three successive Presidents brain to provide a novel perspective on young researcher? led the expansion of the IoN, which has grown (Colin Blakemore, Nancy Rothwell and Richard the critical contribution of dopamine A/ Keep asking questions! And stay to be one of UK’s largest neuroscience groups, Frackowiak), Colin gave the best of himself under to individual differences in learning positive – there are lots of ups and with a focus on research in rodents, primates and four BNA leaders (Richard Frackowiak, Graham and memory. downs in research, but it’s worth it in humans. More than a third of our academics are Collingridge, Trevor Robbins and David Nutt) – he Clinician scientist Rumana Chowdhury Q: What did you think when you heard the end when you discover something clinicians, spanning disciplines of neurology, clinical was one of few BNA stalwarts who wore different (UCL) won the BNA’s Postgraduate you’d won the BNA award? meaningful. neurophysiology, neurosurgery and psychiatry, hats within the organisation. His sincerity, wisdom Award 2013. A/ I felt very excited! It is a real honour for Q: What do you enjoy doing outside underpinning translational neuroscience and the and thoughtful approach were the hallmarks during the BNA to recognize my doctoral work. science and medicine? Wellcome Trust Centre for Translational System his years of dedication to the BNA. Many will miss Q: What did you discover in your I am also grateful to my supervisors, A/ I’m a keen musician. I play the piano Neuroscience, initiated by Colin. Colin and his infectious wide smiles. He is survived research? Professor Emrah Duzel and Professor Ray and guitar and love watching live music. Colin made significant contributions to our by his wife Christine Ingram, and children, Alex, A/ The dopamine Dolan, who guided my work and were a understanding of the hypothalamo-pituitary axis Miles and Rachael. declines as part of the normal ageing constant source of inspiration. (HPA) and corticosteroid neurobiology. During his PhD studies at the Babraham Institute (1982–86), Raj Kalaria (BNA National Committee 1998–2000; Honorary Secretary he made some of the first recordings of electrical 2000–04) is Professor of Cerebrovascular Pathology (Neuropathology) in the Institute for Ageing and Health, Newcastle University, activity and membrane ion currents in pituitary Newcastle upon Tyne NE4 5PL. Q&A: Elina Jacobs the development of myelination in the to do human neuroscience and learn more cells. He was particularly interested in how CNS, and the first thing I discovered about human brain imaging techniques. variations in corticosteroid secretion might alter was what an amazing model organism It’s been a steep learning curve since my HPA activity to trigger certain psychiatric disorders the zebrafish is for neural development. background is mostly in biology, but I’m associated with stress, anxiety and depression. Zebrafish embryos are completely really enjoying it! Remarkably, he also successfully managed two Join the BNA... transparent, and being able to look down Q: What are your long-term plans? other creativities: one was in neurotechnology, with We’re growing fast, the microscope at a living organism and A/ I like the idea of an academic career a view to developing novel approaches that can see its developing CNS shine in different since that would allow me to combine be applied to the development of neuroprosthetic so why not join us? colours thanks to fluorescent genetic research and teaching, I have worked as devices (e.g. retinal implants and cortical markers captivated me throughout a tutor for school kids before and really neurochips); the second was in neuroinformatics, In addition to discounted journals and books my project. enjoyed it. I’ve been lucky to have some grid-based analysis and databasing facilities and other occasional ‘special offers’, the benefits Q: What did you think when you heard great teachers and mentors, and I’d like (the CARMEN e-science platform, developed of membership include reduced registration fees you’d won the BNA award? to do the same for others. through EPSRC funding and currently supported or free admission to BNA events, regular news A/ I was ecstatic, of course! And it gave In terms of what research I’d like to do, by the BBSRC) for neurophysiological data. updates, prizes, bursaries and more. me a confidence boost as well – if I can I am fascinated by the interaction of As a consequence, Colin had a key role in the Elina Jacobs (Edinburgh) won the achieve an award by doing what I love, nature and nurture and how they affect development of neuroinformatics in the UK From £35 for students, £69 for full members. BNA’s Undergraduate Award 2013 for her then hopefully that means that I’m on the mental health. I want to understand and he chaired the Data Sharing programme See www.bna.org.uk/about/benefits-of- dissertation ‘Imaging myelination in vivo right track by aiming for a research career. how genetic and developmental of the International Neuroinformatics membership.html using zebrafish’. Q: What are you doing now? predispositions combine with every-day Coordinating Facility. A/ I’m at UCL on the Wellcome Trust life stressors, and how that can lead to With incredible drive, determination and Q: What did you discover in your four-year Neuroscience PhD Programme. mood disorders like depression. dedication, he took serious interest in wide-ranging research? I am currently doing my first rotation in Q: What do you enjoy doing outside aspects of neuroscience in Newcastle. As Director A/ I did my research in David Lyons’s lab Sarah-Jayne Blakemore’s group at the science and medicine? of the IoN, he was perceptive and had vision to at the Centre for Neuroregeneration under Institute of Cognitive Neuroscience. After A/ I enjoy playing piano and singing, advance the neurosciences beyond the North-East. the supervision of Tim Czopka. The lab having looked at development in a model dancing salsa, and I love travelling. As well as developing collaborations with the RIKEN uses zebrafish as a model to understand organism, I wanted to know what it’s like Brain Science Institute in Japan, last November Colin led an impressive group to establish various

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