Pick my Brain!

In this column, I ask neuroscience professors from around the world the same five questions. Read on to learn more about their research, careers and goals for neuroscience in the future.

14.9.2019

Interview with Professor Dr. Sigismund Huck, MD

Center for Brain Research, Division of Pathobiology of the Nervous System

Medical University of Vienna

Professor Dr. Huck is the President of the Austrian Neuroscience Association (ANA). He worked at the Center for Brain Research. He is a guest scientist after retirement at the Division of Pathobiology of the Nervous System.

1. What inspired you to pursue neuroscience as a career? 

As an MD I was initially interested in drugs acting on the nervous system. This led to a more general interest in the function of the nervous system.

2. What do you think is the most important goal of neuroscience research? 

A comprehensive understanding of how the brain handles all its different tasks.

3. What are the main topics and goals of your research?

Composition and function of nicotinic receptors in health and disease.

4. What accomplishment do you think is the most important out of your own research? 

We got quite some insights in the function of neuronal nicotinic receptors.

5. What do you hope to accomplish in the next 10 years in the field of neuroscience? 

Well, as a formally retired researcher, and in reasonable good health, I want the student I am guiding to successfully complete the project we are working on.

 6. Bonus question: What is your advice to a teenager who wants to learn more about neuroscience?

The internet is already a valuable source for information. However, you must be quite fluid in English. See e.g. https://www.dasgehirn.info/https://www.brainfacts.org/https://brainconnection.brainhq.com/

9.4.2019

Interview with Dr András Lakatos, MD, PhD, MRCP

Dr. András Lakatos is leading an MRC funded regenerative neurobiology laboratory at the University of Cambridge, and he is also a practicing consultant clinical neurologist. Should you be interested in his neuroscience research, you can follow his group at @LakatosLab or at www.lakatoslab.co.uk.

1. What inspired you to pursue neuroscience as a career?

Several things and people. I was initially inspired by my parents who are medics too, so chatting over the Sunday roast at the table had put me on this track probably at the first place. Great lectures delivered by excellent neuroanatomists Katalin Köves and Béla Halász in Budapest have certainly influenced me. I can recall when a dogma-breaking paper was published by Fred Gage’s group at the end of the 90’s. This had opened up new directions and hopes in neural repair strategies and has further attracted me to the field. My curiosity in neurosciences had been fuelled during my PhD, postdoc and clinical years in the UK by several renowned neurobiology professors, mentors and later collaborators, including Robin Franklin, Sue Barnett, James Fawcett. You need to have people around, who can inspire you in addition to working on something rewarding.

2. What do you think is the most important goal of neuroscience research? 

I am not sure there is such thing as ‘the most important goal’. There are several subjects in which discovery is equally urgent. This spans from the principles of wiring of the brain to topics such as the mysterious loss of neuronal connections in brain diseases, especially in those common conditions that lead to memory loss (dementia). Perhaps a unifying important goal is to fully explore the previously under-appreciated cellular diversity in the central nervous system, which adds to the functional complexity of the human brain. This may eventually help better understand the precise causes that may disrupt healthy cell functions in disease. 

3. What are the main topics and goals of your research? 

My research group focuses on how non-neuronal cells such as glial cells regulate neuronal functions in health and disease. For long they have been regarded only as support cells for neurons or the ‘brain glue’ hence the Greek name ‘glia’. More recently, it has been fascinating to learn that these cells tightly regulate the connections between neurons apart from maintaining their health. While it emerges that a major glial cell type, the astrocyte could also be detrimental in untreatable and disabling neurological diseases leading to dementia, problems with movements or loss of muscle strength. This includes Alzheimer’s Disease, Parkinson’s disease or Motor Neuron Disease. So it is not surprising that astrocytes have already attracted interest from scientists who are trying to turn these cells from a toxic state to a protective one. In my lab we are working on a ‘molecular switch’ that would make this conversion possible. In particular we use human neurons and glial cells derived from stem cells of patients to make our observations more relevant to human neurological diseases.

4. What accomplishment do you think is the most important out of your own research? 

It has been very rewarding to make some early contributions to the concept that reactive astrocytes – a cell state reflecting responses to injury – is not always detrimental but can also support the neuronal network. Using novel models relevant to human Motor Neuron Disease, we demonstrated where these beneficial pathways could potentially break down. Lately, our research have also contributed to the development of a state-of-the-art human model system in a dish, called the ‘minibrain’ by collaborating with other groups in Cambridge. This has attracted immense interest as models like this have a potential to revolutionize research tools helping to understand human brain function or dysfunction. This is a very exciting development but more research is required until we can fully implement this approach.

5. What do you hope to accomplish in the next 10 years in the field of neuroscience? 

The development of new tools in neurosciences has been accelerating, especially in the last two decades, which also had an impact on our scientific work. For instance we use single cell gene expression analysis that allows us to identify individual cell types or to discover new ones at a larger scale and to predict their specific function at ease. In addition, novel gene-manipulation techniques have been developed that can more accurately help elucidate important cell functions in our studies. Now, in the lab we can use these approaches to see how important observations made in rodent models relate to human biology, this is called ‘translational research’. Nevertheless, human stem cell based models in a dish, such as the ‘minibrain’ provide an unprecedented opportunity allowing for making new discoveries relevant to human brain function in health and in disease.

Bonus question: What is your advice to a teenager who wants to learn more about neuroscience?

Having chats with your biology teacher in school is a good start. I was lucky to have a fantastic teacher, Feri Kecskés who thought us the basics of cell biology in Budapest when I was a teenager. You can get local experts to give talks in your school on a subject of your interest. My excellent young colleagues in the lab enjoy visiting schools in Cambridge and to talk to pupils about our research, raising their awareness and interest neurobiology. However, fundamentally, you don’t want to commit yourself studying only neuroscience at this stage, and you would be better off exploring how things work in biology in general. Fortunately, there are a number of websites out there, which can help you achieving this. In specific, following biologists and neuroscientist via Twitter is now almost a ‘gold standard’ in getting up-to-date information. Our University also organizes a science festival each year, which is a fantastic opportunity to start engaging with sciences and neuroscience as a teenager in particular.


28.3.2019

Interview with Dr. Andreas Lieb, Ph.D

Department of Clinical and Experimental Epilepsy, Queen Square Institute of Neurology

University College London, London, England

Dr. Andreas Lieb studied Pharmacy at the Leopold Franzens University Innsbruck. He acquired his PhD at the Institute of Pharmacology and Toxicology, also in Innsbruck, mainly focusing on the detailed biophysical characterization of disease causing mutations in the low voltage activated Ca2+-channel Cav1.3. In October 2014 he moved to the Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, where he develops novel gene therapeutic treatment strategies targeting refractory epilepsy. Currently he is optimizing different approaches for first in human use.

  1. What inspired you to pursue neuroscience as a career? 

During my childhood I was always amazed by nature. I even remember the first time in my life when I was allowed to stay up late (I was fairly young so I mean here later than 8pm), in order to watch the Austrian documentary series UNIVERSUM together with my dad. During my school education, it emerged early that if I wanted to enrol in university, it would be a rather advisable decision to go for a natural science related field. So I studied Pharmacy, just, because I could not decide between medicine and chemistry, and thought it a wise choice (turned out to be one of the best ones I ever made). During my studies I was amazed by the manifold drug actions on the brain. So what inspired me to pursue neuroscience as a career? Wow, easy question, hard to answer. I think why I decided in the end to focus on studying neuroscience (I am also interested in other organs), is, because 1) the function of the brain is well understood, but it is hardly known how it works, 2) there is an overwhelming need of novel treatment strategies, targeting brain disorders, and 3) these two facts provide an amazing research environment, where, through identification of novel treatment strategies, we are able to gain more insight into how the brain works, and can further develop novel treatment strategies. In short, isn’t the brain the most amazing organ developed during mamal evolution?

2. How is research work in the UK different from Austria from your perspective/experience? 

In general it has to be considered, that this is a hard question for me to answer, as I have been in different career stages in Austria in comparison to the UK. After a successful PhD-study in Innsbruck, I moved to the Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology in London, totally overwhelmed by the size of the city itself. Although I had knowledge about neuroscience already, I was overwhelmed by the sheer amount of new information (in principle I changed the research field between my PhD-studies and my Postdoc phase). From my perspective, there are two major differences between research in the UK and Austria. First, research in the UK is much more visible to the public. That means, that research is much more communicated to the general public, and it is also much more present in normal day live. This happens mainly via charities like “Epilepsy Research UK”, or “Cancer Research UK”, which themselves fund a lot of research. This may probably be also the main reason why research is rather preserved as a goal of the general public, than of a small elite. This goes along with the second big difference, which is the amount of money which is spent on research. This opens up a lot of opportunities and are the reason the UK can do cutting-edge research. Most people will now come up with the argument, that, yes, the UK has a bigger population than the Austria. Nevertheless, I think that the funding volume of Austria is much too low, and should be increased substantially. In my opinion, Austria has a huge potential to get one of the leading countries on research, but yes, this comes with a price. I really think it is worth spending the money for research!

3. Has research in the UK experienced any changes because of Brexit? 

One of the major strengths of research in the UK is, that the UK attracts very bright minds from all across the world. In contrast, “take back control of the boarders” was one of the main reasons for Brexit. This is a fundamentally different concept that may have a huge impact on research personnel in the future. In addition, the EU is a major research funder and it is not clear at the moment, whether the UK will have access to European grants in the future.

4. What are the main topics and goals of your research? 

Around 50 million people worldwide have epilepsy. Of those, around 30% (that’s 15 000 000) continue to experience seizures despite optimal medical treatment. This does not only have a substantial impact on their normal day live, but also significantly increases the risk of sudden unexpected risk during epilepsy. Since I am in the UK my major goal is to be involved in the development novel treatment strategies for refractory epilepsy.

5. What do you hope to accomplish in the next 10 years in the field of neuroscience? 

My recent research was focusing on development of novel gene therapeutic strategies targeting refractory epilepsy. It would be amazing to see one of them enter the clinical trial phases, or even be licensed as a novel medicine.

14.3.2019

Interview with Professor Alexandre Pouget

Centre Medical Universitaire, Dept. des Neurosciences Fondamentales

University of Geneva, Geneva, Switzerland

Professor Alexandre Pouget is a full professor in the department of basic neuroscience at the University of Geneva where he leads the computational cognitive neuroscience laboratory. His research focuses on general theories of representation and computation in neural circuits with a strong emphasis on neural theories of probabilistic inference. He was awarded the Carnegie Prize in Brain and Mind Sciences in 2016. He is also the co-founder of the International Brain Laboratory, a consortium of 21 laboratories across the world whose goal is to develop the first brain wide theory of decision making. 

1. What inspired you to pursue neuroscience as a career?

My dad. He was a highly educated man, extremely smart but he believed in god. To me, it seemed obvious that the concept of god, and I’m talking about the omnipotent god who can have a causal impact on your life and imposes a set of divine moral principles, was just a construct of the human mind to deal with existential questions. Admittedly, it’s not easy to find satisfying answers to these issues… Anyway, I lost every debates with him because I didn’t know enough about the brain to make a strong case for my view. So I became a neuroscientist! This also turns out to be the science that allowed me to address all the fundamental questions that I care about: do I have free will? Why do we have feelings? Why would cave men 30’000 years ago feel an urge to paint the wall of the Chauvet cave (https://www.grottechauvet2ardeche.com/) and why would they feel compelled to preserve these paintings over thousands of years? What’s the function of consciousness? Can a mind be eternal? 

2. What do you think is the most important goal of neuroscience research?  To understand how the brain controls behavior. 
Note that I’m not saying that everybody should study this but, from my point of view, this is the essence of what neuroscience is about. Curing mental diseases is obviously a laudable goal and one that deserves strong support but understanding the neural basis of the mind is the ultimate scientific question. 
It’s not like other sciences do not address fascinating questions but they are not about you. For instance, I love physics because it shed light on the nature of the universe and the structure of matter but none of that explains why humans have moral principles or why a human mind can do mathematics. Ultimately, all my mental experiences, everything I believe and feel, is just the result of my neurons being active and exchanging molecules and electrical impulses. In my opinion, how this leads to my mental experiences and behavior supersedes all other scientific questions. 

3. What are the main topics and goals of your research?
We’re trying to understand general principles of computation in the brain, regardless of the domain. It’s like asking what are the general principles that allow computers to do everything they do. Alan Turing answered that question a while ago. We don’t have an answer for the brain yet. 

4. What accomplishment do you think is the most important out of your own research?
Making progress toward understanding how the brain perform probabilistic computations. Beliefs in the brain are probabilistic in the sense that the brain does not simply represent what it believe in but, instead, it computes the probability that its belief or percept, is correct. Indeed, in most situations, the sensory information and our past experiences are not sufficient to know for sure what to believe. Using probability distribution is much more efficient in such situations but how the brain performs such probabilistic reasoning is still very much unknown.

5. What do you hope to accomplish in the next 10 years in the field of neuroscience? 
Understanding the neural basis of complex decisions such as the ones involved in deciding which career to pursue or who to vote for. I’m also hoping to change the way we do neuroscience by fostering large scale collaborations similar to the CERN in physics. Our first attempt, the International Brain Lab, https://www.internationalbrainlab.com/ was launched in Sept 2018.

Bonus question: What is your advice to a teenager who wants to learn more about neuroscience? Imagine you had been born at the end of the 19th century and you were interested in science, which field should you have picked? Clearly, Physics. Physics went through a revolution at the beginning of the 20th century. Being part of it must have been incredibly exciting. Likewise, Biology was the way to go in the middle of the 20th century. Now is the time for neuroscience and AI. And unlike the other sciences, it will tell you about who you are. Note that many physicists and mathematicians like Newton, Laplace, Helmholtz or Poincare wrote extensively about perception, thinking and reasoning. Had they been born in the 21st century, I bet they would have all become neuroscientists. 
As to how you should go about it, it’s pretty easy. Take online courses, read tons of books and try to join a lab to start doing research as early as possible. Your best ideas will be shaped during your early years. The earliest you confront yourself to big questions, the better. 

3.3.2019

Interview with Dr. Bruno Benedetti, Ph.D

Senior PostDoc, Institute for Experimental Neuroregeneration, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS)

Paracelsus Medical Private University, Salzburg, Austria

Graduating with honours after a master in Neuroscience at the International School for Advanced Studies (SISSA) & University of Trieste, Dr. Benedetti did his PhD in Medical Neuroscience at the Humboldt University, Berlin and International Graduate Program of Medical Neuroscience, Charité, Berlin. He did his dissertation in the laboratory of Helmut Kettenman (Max Delbrück Center for Molecular Medicine, Berlin Buch), graduating with honours. He started his postdoctoral training at the Medical University of Innsbruck in 2012, working on calcium channels, muscle physiology and motor dysfunctions related to disorders of the central nervous system. He moved to Salzburg in 2016 and currently focuses his work on nervous tissue regeneration after spinal cord injury. Dr. Benedetti is a core member of the Verein für Lokale Wissenschaftskommunikation, local coordinator of the “Wissensdurst Festival”: Austrian Festival of Science. He is also extended board member of the Austrian Neuroscience Association (ANA) and president of the Young ANA network.

  1. What inspired you to pursue neuroscience as a career? 

As kid, I was curious about biology and about the brain, but commitment for neuroscience only emerged from a jumble of interests and possibilities at the end of my undergraduate education. I remember travelling Europe on a budget, taking interviews for a PhD position while trying to keep up with a part-time job and wondering if anything would come out of all that effort. Luckily, I entered an excellent training program and had the opportunity to work in a good laboratory, for a great mentor. Great mentorship and a rewarding postgraduate experience are the main factors that changed curiosity into lifetime commitment.

2. What do you think is the most important goal of neuroscience research? 
Science should aim to improve the quality of life through a better understanding of nature and a better control of its processes. I believe it is most important to entertain projects with focus on such goal, but I would find hard to set priorities. It is rather responsibility and merit of each scientist to honestly question their goal’s relevance. As for popularity: the perceived relevance of scientific topics is affected by economic interests, but this should not be the ideal paradigm by which the quality of research projects are judged. Combining relevance for improvement of life quality and economic relevance, in my niche, it would be very attractive to improve the capacity of regeneration of damaged brain tissue, to enhance cognitive skills, and to significantly prolong the healthy life of the brain. So, perhaps, those are my top three.

3. What are the main topics and goals of your research? Most neurons in our brain are generated before birth. After birth, they grow and mature, but they no longer divide: they do not generate new daughter cells. Only in few small areas of the brain known as “neurogenic niches” some neuronal precursors remain immature and proliferate also during adulthood, constantly giving birth to new neurons. Such new neurons only colonize few specific brain areas. As result, few “lucky” adult brain regions benefit of newly added neurons and the rest of the brain has to be content with the same old neurons from birth to death. At least, this is what everyone thought until few years ago. Quite recently it emerged instead that several brain regions, which are not neurogenic niches, also contain latent neuronal precursors. Strikingly, precursors outside the neurogenic niches do not proliferate. Therefore, they are an exhaustible pool of cells and they are used up with age. After such discovery, scientists speculated about what the role of the latent precursors may be. On one hand, these cells could be a valuable but limited resource to be used as “spare parts” for the aging brain. Alternatively, the brain could need the precursors to generate an entirely new type of neurons adding complexity to the pre-existing networks. Recently it was my honor to contribute determining the fate of the latent non-proliferative precursors in the adult brain. So far, our results imply that the latent precursors outside the neurogenic niches mature in a new type of neuron, functioning differently from their preexisting neighbors. What is the role of these cells for brain functions? What will happen to the brain if it did not have such precursors or if it run out of precursors too quickly? We are currently searching for answers. Stay tuned!

4. What accomplishment do you think is the most important out of your own research?  The developing research on non-proliferative precursors (see previous paragraph) have great potential. While the relevance of these cells for the brain function is so far speculative, I suspect that they may be very important and exploitable for the betterment of our health and cognitive skills. Being among the first to functionally characterize these cells was a great privilege. Finding how to exploit this resource for human health will be an exciting challenge. As purely personal accomplishment, scientific research helped me gaining better appreciation for excellence, patience, humility and teamwork. The most tangible fruit of a job well done is an excellent publication. However, there is a lot of fulfillment in the personal growth that makes the experience consistently repeatable.

5. What do you hope to accomplish in the next 10 years in the field of neuroscience? I want to become independent and established. In term of scientific projects, this translates in my current attempts to refine a strategy for fine-tuning the brain (cortical) plasticity. I am endeavoring in such direction with particular interest toward recovery from spinal cord injury. The goal for the next years is to deliver reliable plasticity-inducing paradigms for treatments that can be customized according to individual needs and pathophysiological context.

Bonus question: What is your advice to a teenager who wants to learn more about neuroscience?Neuroscience is a broad subject that can be approached with different perspectives. You might decide to study neuroscience as a biologist, medical doctor, psychologist, physicist, engineer etc. While the knowledge of one profession is sufficient to carry out a job, excellent research will greatly benefit of a broader education. Since you, inquisitive teenager, are probably busy deciding how to shape up your future, I suggest to choose the course of education which is best suited to your skills and taste, but keep exploring other disciplines, to help you understanding matters of neuroscience that are not explained by yours.


2.28.2019

Interview with Dr. Tiago Gonçalves, Ph.D

Assistant Professor, Department of Neuroscience and Stem Cell Institute

Albert Einstein College of Medicine, Bronx, NY, USA

Dr. Gonçalves obtained a BSc in Physics from Imperial College, London and a PhD in Neuroscience from the University of Göttingen (Germany). He did his dissertation research work in the lab of Prof. Walter Stühmer at the Max-Planck Institute for Experimental Medicine. He moved to California for his postdoctoral training in the labs of Dr. Carlos Portera-Cailliau at UCLA and Dr. Fred Gage at the Salk Institute. Dr. Gonçalves joined the faculty of the Albert Einstein College of Medicine in 2016.

1. What inspired you to pursue neuroscience as a career?  I’ve always wanted to work in the field of science or engineering and I’ve always had an interest in how the brain works, but before the final year of my undergraduate studies I never thought I would pursue a career in neuroscience. I studied physics and one of the elective courses for our final year was “Biophysics of brain cells and networks”. The course and the professor were really good, and that really convinced me to pursue a PhD in this field. 

2. What do you think is the most important goal of neuroscience research?  I think there are different goals, depending on whether you approach it form the medical perspective or the fundamental science perspective. From the medical side, I think there’s an acute need for new approaches for treating neurological and mental health disease. These range from schizophrenia to Alzheimer’s and we have a still very limited set of tools to address these diseases. From the science side,  I there’s a lot that we still don’t understand about how the brain works, although we have made tremendous progress over the years. For example, I think most researchers would agree that we still have a rudimentary understanding of how memories are made, stored and recalled in the brain. How how neurons choose which connections to make.

3. What are the main topics and goals of your research?  I study the hippocampus, a part of the brain that is involved in memory and learning. One particular aspect about the hippocampus is that it is of the few areas to add new neurons through adulthood. I am fascinated by the concept of adding new neurons to the brain because of what it can potentially teach us about using new neurons for brain repair (what is known as regenerative medicine). How do these new neurons carve out space for themselves and make connections? Are these connections meaningful? Do they dislodge the synapses of older neurons and compete with them?

4. What accomplishment do you think is the most important out of your own research? One of our recent findings was that new neurons undergo a period of overgrowth and pruning during their development. In a way, we suspected this already. It seems that most, if not all neurons do it. But we were able to image this process as it happens, which opens up a lot of new questions. The process of establishing new connections or synapses is very complex and involves multiple molecular pathways, but why do neurons need to “try out” new dendritic branches and why do they remove them? There’s some type of optimization going on here, but we don’t know what these new neurons are optimizing for.

5. What do you hope to accomplish in the next 10 years in the field of neuroscience?  I think I would like to see us be able to transplant new neurons into the brain and have some control over the type of neurons they become, and the connections that they make. Many labs are working on this and there’s even some clinical trials in humans, but I think everyone would agree that these are still the baby steps of regenerative medicine, as far as the brain is concerned.

Bonus question: What is your advice to a teenager who wants to learn more about neuroscience?Try to work in a lab! If you’re interested in science I think it’s great to try and find a lab that will allow you to do an internship  over the Summer or after classes. We always try to accommodate requests from high schoolers.

2.16.2019

Interview with Professor Richard Ribchester, Ph.D DSc FPhysiol

Professor of Cellular Neuroscience, Euan MacDonald Centre for MND Research and Centre for Discovery Brain Sciences 

Biomedical Sciences, University of Edinburgh, Scotland

Professor Ribchester obtained a BSc with Joint Honours in Chemistry and Zoology from the University of Durham and a PhD in Experimental Neurology from the University of Newcastle-upon-Tyne. He did postdoctoral research at the University of Colorado Medical School in Denver, and at the Institute of Physiology, University of Oslo.

1. What inspired you to pursue neuroscience as a career? 
Thinking back as far as I can, my first inspiration probably came from my father, who was a career soldier in the Royal Signals, the telecommunications regiment of the British Army. When I was about 8 years old, we were on a family picnic and for no obvious reason that I can recall, he sat me on the bonnet (hood) of the family car, had me cross one leg over the other and then demonstrated the myotatic reflex by tapping my hanging leg just below the kneecap. I found the involuntary nature of this ‘knee-jerk’ reflex both fascinating and highly amusing. From then, I developed my childhood delight with knowledge generally, gradually drifting more towards science than arts and humanities.  I had difficulty deciding whether to pursue chemistry or biology as I had become particularly interested in both (I read for a joint Honours degree in both subjects at Durham University in the early 1970’s). In my zoology classes at Durham I found the physiology of neuromuscular junctions and neuromuscular transmission to be especially interesting (along with other topics, like mitochondrial biochemistry). Through a series of happenstances, after I graduated I was offered an MRC Research Studentship to study neuromuscular transmission in a mouse model of muscular dystrophy, at the Muscular Dystrophy Research Laboratories in Newcastle-upon-Tyne. I had an inspirational (and patient!) PhD supervisor, Professor John B Harris. I was also inspired by the energy and enthusiasm of Professor Clarke Slater. Thus, I became completely hooked on synaptic physiology. I wrote a successful 2-year fellowship application for my first postdoc, to work with Professor Bill Betz at the University of Colorado Medical School and I worked under his inspiring, rigorous and expert guidance on neuromuscular synapse elimination. It was during that period that I “discovered” neuroscience as a nascent discipline, independent from physiology. (I attended the fifth annual meeting of the Society for Neuroscience in St Louis in 1978; at the time it seemed like a huge conference, with over 5,000 delegates. Nowadays, SfN meetings have over 30,000 attendees). I then wrote a successful one-year fellowship application to work with Professor Jan Jansen in the Physiology Institute at Oslo University, where I worked from 1979-1980. We were studying the specificity and plasticity of monosynaptic and polysynaptic connections on motor neurones in the embryonic chick spinal cord (including those mediating the myotatic reflex) and from which we made the first intracellular microelectrode recordings in vivo. That was a very exciting year, as Jan was incredibly inspiring and what we were doing was so new. Every day ended with a detailed discussion of that day’s experiment and a decision on what experiment we therefore needed to do the following day. We progressed very rapidly and steadily with that approach, both technically and scientifically. During that year I applied for and was offered a Lectureship (assistant professorship) in Physiology at Edinburgh University. My evolution to calling myself a “neuroscientist” rather than “neurophysiologist” continued from then, although I do still have most fascination for the anatomy and physiology of neuromuscular junctions and other synapses. I have been on the academic staff of Edinburgh University since 1980 and I am now Professor of Cellular Neuroscience. I received a great deal of inspiration and support from senior colleagues, leading to that promotion, not least from Professor Richard Morris, who headed the Department of Neuroscience that I joined in the 1990’s (now integrated into the Deanery of Biomedical Sciences).  I still enjoy combining both research and teaching, and one of my greatest sources of satisfaction has been my part in training (and hopefully inspiring) my PhD students and postdocs, some of whom have developed successful careers as leaders in their fields.

2. What do you think is the most important goal of neuroscience research? 
A glib answer to this is “to understand the brain”. Defining what that means exactly is more  problematical. I am constantly mindful of an interview I saw on TV in the early 1990’s with a contemporary Oxford philosopher (whose name I have alas forgotten), during which he pointed out that even if we understood everything there is to know about the anatomy and physiology of the brain, sufficient to enable us to build an exact replica, then that machine would most likely be conscious: but we would still not understand why! More prosaically, Bernard Katz, late doyen of our field,  remarked in his Fenn Lecture delivered in 1994 that neuromuscular junctions are  “experimentally favourable objects, whose study could throw considerable light on synaptic mechanisms elsewhere”. This became the most powerful principle guiding my research. Many years earlier, my former postdoc mentor Bill Betz, who received training himself as a postdoc in Katz’s laboratory in the late 1960’s, once mentioned in the lab another remark Katz had made: “we do what we can with what we have”. I consider that also to be an excellent guiding principle for contemporary neuroscience. Centuries earlier, Galileo urged that we should “measure what can be measured, and make measurable what cannot be measured”, which is similar goal, for all science. 

3. What are the main topics and goals of your research? 
I retain a complete fascination with every aspect of the biology of neuromuscular junctions and I am at my happiest when I am doing experiments on them in the lab myself (when I have time). Right now, I have three ongoing projects: the first an MRC-funded major project on the pharmacology and toxicology of organic solvents at neuromuscular junctions, which is relevant to a particular health issue in southern Asia. The second project, funded by MNDA, involves developing tools for visualisation of neuromuscular junctions in situ, ultimately with a view to enabling microendoscopic imaging to be used in research and diagnosis of neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS; called Motor Neurone Disease in the UK). My third parallel project is on fundamental mechanisms of neuromuscular function and excitability, utilising the considerable opportunities for combining powerful techniques of genetics and physiology in studying neuromuscular junctions in larval fruit flies (Drosophila). I am firmly of the view that insights into mechanisms and treatment of presently-incurable neurodegenerative diseases, especially ALS, will only come from achieving deep understanding of fundamental mechanisms in motor neurone and synaptic biology.

4. What accomplishment do you think is the most important out of your own research? 
This is a difficult one to answer, since good scientists are always behoven to be modest: all of our findings and explanations will ultimately be replaced with something better or more accurate. I have been fortunate to stumble on a few things, serendipitously. One was during my first postdoc when I noticed the dual innervation of rodent fourth deep lumbrical muscles by separate motor axons running in the sural and tibial nerves. This opened up possibilities for several crucial experiments that I subsequently carried out, with a succession of excellent students and postdocs, demonstrating the influences of neuromuscular activity on synapse elimination during development or regeneration of neuromuscular connections. Another has been my long association and collaboration (since 2000) with Professor Michael Coleman, now head of the John van Geest Centre for Brain Repair in Cambridge, on the mechanisms of slow axonal and synaptic degeneration following axotomy in the spontaneous mouse mutant that is now known as Wallerian-degeneration-Slow (WldS), which was discovered serendipitously in Oxford in the late 1980’s, by Hugh Perry and Michael Brown. I and my then-student Tom Gillingwater (now Professor of Anatomy in Edinburgh University) developed a conceptual model of neurodegeneration  (“compartmental neurodegeneration”) which has helped guide our thinking about neurodegenerative mechanisms and which I hope has influenced others. More recently, it has been satisfying to discover how cyclohexanol acts on neuromuscular transmission, and how derivatives of tetanus toxin can be used to vitally-stain NMJs and image them with a confocal microendoscope. I am intrigued at present by my observations on excitability of muscle fibres in larval Drosophila. Time (and more experiments) will tell what the fundamental significance of these may be. I also feel very gratified by the accomplishments of the PhD students I had the privilege to nurture during their formative scientific years. But I feel most satisfied by the work I did with the University of Edinburgh and a local philanthropic family, enabling us to establish in 2008  the Euan MacDonald Centre for Motor Neurone Disease Research, now directed by Professor Siddharthan Chandran. This research centre has brought together a substantial group of researchers in Edinburgh and elsewhere in Scotland, and we all work together on both the clinical and scientific challenges that accompany the devastating spectrum of illnesses that is ALS.

5. What do you hope to accomplish in the next 10 years in the field of neuroscience?  I will probably be retired by then (I am presently 65 years old), although I hope my mind will still be in sufficient shape to contemplate NMJs and to enjoy the accomplishments of others, including my former trainees and colleagues, who study synaptic structure and function. In the shorter term, I’d like to productively scratch my itch to understand excitability in larval Drosophila NMJs. I also have a burning desire to plug a hole I’ve identified in our understanding of non-linear summation of synaptic potentials at NMJs, in relation to muscle fibre size and synaptic strength. I’ve been putting off the voltage-clamp experiments I need to do on these for far too long….!