Tag Archives: neuroscience

Winners of 2017 Brain Prize announced – Peter Dayan, Ray Dolan and Wolfram Schultz

The one million Euro Brain Prize, awarded by the Lundbeck Foundation in Denmark, has gone to three neuroscientists for their work understanding the mechanisms of reward in the brain. The winners are:

  • Peter Dayan – Director of the Gatsby Computational Neuroscience Unit, University College of London
  • Ray Dolan – Director of the Max Planck Centre for Computational Psychiatry and Ageing
  • Wolfram Schultz – Professor of Neuroscience and Wellcome Trust Principal Research Fellow at the University of Cambridge

Collectively, their work examines the ability of humans and animals to link rewards to events and actions. This capacity has been a foundation of our survival, but can also be the root of many neurological and psychiatric disorders, such as addiction, compulsive behaviour and schizophrenia. In order for the successful survival and reproduction of a species, an animal must be able to make decisions that avoid danger and bring benefits (such as food, shelter, etc.). T decision-making requires predicting outcomes from environmental clues and previously learned responses. For instance, certain smells may indicate that an animal should prepare to chase prey, or to avoid a fruit item. The brain plays a key role in this decision making and learning, and at the centre of this is the neurotransmitter dopamine.

wolfram-schultz

Wolfram Schultz

In the 1980s, Professor Wolfram Schultz developed a way of recording the activity of neurons in the brain that use dopamine to transmit information. He found that the dopamine neurons would respond whenever a monkey was given fruit juice reward. Schultz then showed the animals different visual patterns; whenever a certain pattern was shown, the monkey would receive a reward. After a time the dopamine neurons began to respond to the visual pattern, rather than the juice reward (response to the juice reward itself declined over time). Conversely, when no reward was given (after the correct pattern was shown), the dopamine neuron activity decreased below normal levels. If the reward was given at another time or was bigger than expected, the dopamine neuron activity would spike (1).  This was the first clear demonstration of the neurological basis of one cornerstone of learning theory in Comparative and Behavioural Psychology; Pavlovian conditioning (2).

Building on Schultz’s work, Peter Dayan found the pattern of activity from dopamine neurons described by Schultz resembled the ‘reward prediction error’.  This signal is the difference between predicted and actual reward resulting from an action or event. It continuously updates according to the result of new events and outcomes. Dayan would go on to work with Schultz to create computational models investigating how the brain uses information to make predictions and how this information is updated when new or contrasting information is presented.

Peter Dayan

Peter Dayan

Schultz explains the reward prediction error and resulting learning in the following analogy:

I am standing in front of a drink-dispensing machine in Japan that seems to allow me to buy six different types of drinks, but I cannot read the words. I have a low expectation that pressing a particular button will deliver my preferred blackcurrant juice (a chance of one in six). So I just press the second button from the right, and then a blue can appears with a familiar logo that happens to be exactly the drink I want. That is a pleasant surprise, better than expected. What would I do the next time I want the same blackcurrant juice from the machine? Of course, press the second button from the right. Thus, my surprise directs my behavior to a specific button. I have learned something, and I will keep pressing the same button as long as the same can comes out. However, a couple of weeks later, I press that same button again, but another, less preferred can appears. Unpleasant surprise, somebody must have filled the dispenser differently. Where is my preferred can? I press another couple of buttons until my blue can comes out. And of course I will press that button again the next time I want that blackcurrant juice, and hopefully all will go well.

Which button to push?

Which button to push?

What happened? The first button press delivered my preferred can. This pleasant surprise is what we call a positive reward prediction error. “Error” refers to the difference between the can that came out and the low expectation of getting exactly that one, irrespective of whether I made an error or something else went wrong. “Reward” is any object or stimulus that I like and of which I want more. “Reward prediction error” then means the difference between the reward I get and the reward that was predicted. Numerically, the prediction error on my first press was 1 minus 1/6, the difference between what I got and what I reasonably expected. Once I get the same can again and again for the same button press, I get no more surprises; there is no prediction error, I don’t change my behavior, and thus I learn nothing more about these buttons. But what about the wrong can coming out 2 weeks later? I had the firm expectation of my preferred blackcurrant juice but, unpleasant surprise, the can that came out was not the one I preferred. I experienced a negative prediction error, the difference between the nonpreferred, lower valued can and the expected preferred can. At the end of the exercise, I have learned where to get my preferred blackcurrant juice, and the prediction errors helped me to learn where to find it.

Professor Ray Dolan’s work has involved imaging the human brain in order to understand the mechanisms for learning and decision-making. Advancing the work of Schultz and Dayan, he showed that the reward prediction error can account for how humans learn, and the role that dopamine plays within it. He has collaborated with Dayan for the past decade to investigate human motivation, variations in happiness, and human gambling behaviour.

Ray Dolan

Ray Dolan

Schultz continues to study both animals and humans, using neuroimaging to study changes in neuron signals in Parkinson’s patients, smokers and drug addicts. The more we understand the process which leads people to take certain actions, the better positioned we are to intervene.

Professor Sir Colin Blakemore (University of London), chairman of the Brain Prize selection committee said,

“The judges concluded that the discoveries made by Wolfram Schultz, Peter Dayan and Ray Dolan were crucial for understanding how the brain detects reward and uses this information to guide behaviour. This work is a wonderful example of the creative power of interdisciplinary research, bringing together computational explanations of the role of activity in the monkey brain with advanced brain imaging in human beings to illuminate the way in which we use reward to regulate our choices and actions. The implications of these discoveries are extremely wide-ranging, in fields as diverse as economics, social science, drug addiction and psychiatry”.

Primate research remains today an invaluable tool for comparative research into human health and disease. While other animals remain useful as models for such investigations, non-human primates are arguably the best species to be used for such investigations due to their remarkable similarity to humans. The research performed by Schultz, and built upon by Dayan and Dolan, highlight this simple fact and perhaps also exemplifies why critical consideration against the use of non-human primates for research is needed. The Brain Prize also shows how animal and non-animal methods are often used together to build our understanding of how the brain works.

Speaking of Research

  1. Schultz, W., 2015, Neuronal Reward and Decision Signals: From Theories to Data, Physiol Rev 95(3)
  2. Schultz, W. et al, 1993, Responses of Monkey Dopamine Neurons to Reward and Conditioned Stimuli during Successive Steps of Learning a Delayed Response Task, Journal of Neuroscience 13(3)

Understanding the animal, not just its parts

A recent article in the Atlantic, “How Brain Scientists Forgot That Brains Have Owners” is making headlines. The journalist claims that in an article published in early February, titled “Neuroscience Needs Behavior: Correcting Reductionist Bias”, fancy new technologies have led the field of neuroscience astray. The original scientific publication does draw attention to an area of neuroscience that neglects behavior, and outlines the importance of measuring behavior and the brain. However, behavior is not necessary in all areas of neuroscience, and adding behavior to some neuroscience studies could be problematic. Furthermore, the overall goal of the scientific publication was only to suggest that the field of neuroscience is lacking in scientists interested in studying the whole brain rather than the just studying the sum of its parts.

The field of neuroscience is diverse. Take for example the 9 themes at the Society for Neuroscience Conference in 2016:

  1. Development
  2. Neural Excitability, Synapses, and Glia [Neurophysiology]
  3. Neurodegenerative Disorders and Injury
  4. Sensory Systems
  5. Motor Systems
  6. Integrative Physiology and Behavior
  7. Motivation and Emotion
  8. Cognition
  9. Techniques [Technologies]

Glancing over these themes it is apparent that many scientists specialize in different types of neuroscience. Thus, some neuroscientists may study behavior and some may not need to study behavior. For example, neuroscientists investigating questions about technologies or neurophysiology may not need to study behavior at all — it depends on the question. Those only interested in the integration of physiology and behavior would study both the brain and behavior. And those studying cognition or motor systems might conduct experiments on behavior without directly measuring the brain. Whether neuroscientists study brain and/or behavior depends on the research questions they are asking.

Although both publications neglected to discuss the diversity of neuroscience, the main theme of the scientific publication was to change the way scientists interested in the integration of physiology and behavior approach their research questions. Too many neuroscientists focus on using as many new technologies as possible, and then use behavior as an afterthought. The issue here is that some of these new technologies are not yet well understood. Thus, scientists’ research questions using these technologies could be misguided.

Furthermore, behavior is a separate area of research on its own and should never be treated as an afterthought. Thus, the authors suggest that neuroscience needs more interdisciplinary scientists who understand and study the relationships between brain and behavior. It needs scientists that can merge all areas of the field.

All neuroscientists however, no matter their specific question, will help advance the field in different ways. And all neuroscientists do not need to study behavior. However, Interdisciplinary scientists in particular may set the stage for understanding the whole animal and how the brain operates within it. Furthermore, these scientists may help increase the translation of research from animal to human.

The problem of neuroscience without interdisciplinary scientists

A possible issue with scientists only studying one part of the animal (i.e. the brain) is that they neglect the rest of the animal. The authors suggest many neuroscientists only interested in the brain use a top-down approach (brain-behavior) to infer how behavior operates — and this is problematic. A recent experiment on understanding a simple computer demonstrates the potential flaws in a top-down approach. Briefly, computer scientists tested whether the processes of three classic videogames could be inferred by only studying the microprocessor that operated the videogames. In contrast to the brain, the scientists already understood how this computer system operates. After much investigation of the hardware of the microprocessor and how it functions, it remained unclear how the processes in the videogames operated. Thus, by using a top-down approach to understand behavior we will not be able to understand the brain

The bigger problem with measuring the brain and inferring behavior without studying behavior is that you are only studying one part of the animal. Consider the blind men and the elephant:

blind-men-and-the-elephant

Quite simply, if I am blind-folded and given an elephant’s ear then I may think it is a fan. For me to understand and determine that I am holding an elephant’s ear, I would need to investigate the whole elephant — beyond a small part and beyond all parts individually. Interdisciplinary scientists study the “whole elephant.”

However, only studying the ear of an elephant isn’t completely problematic. I can measure what it is composed of, stick electrodes in it to see how it responds, pour different chemicals on it to see how it reacts, measure how it grows over time, test it in different scenarios etc. Thus, I can learn many different aspects about this so called fan. However, what I cannot do is infer its function or purpose without considering the whole elephant. Also, I may be unable to determine which findings are related to the potential functions, and which findings are not related to the potential functions.

The elephant and the blind men, also apply to all experiments using animal models for understanding human biology. If I do not investigate or consider the whole “elephant” I may never determine that the “ear” I am looking at has a similar function to “ears” in many other animals. More generally, if I only study neural circuitry in a mouse without considering the mouse as a whole (anatomy, organs, cells, behavior, environment, development, evolution, etc.) then it won’t help me determine how — or if – the neural circuitry may function similarly in the human.

Development is particularly important — and often forgotten — ­when studying the whole animal. You cannot just study the “ear” of the “elephant” at a specific time point in a specific environment because the structure or function may change over time. Consider the development of a frog:

development-of-a-frog

In the tadpole stage the frog has a long tail for swimming and gills for breathing underwater. As it develops into an adult frog, however, the tail is reabsorbed and the frog exchanges its gills for lungs. Developmental context is necessary for understanding the whole animal.

The necessity of neuroscience with interdisciplinary scientists

Interdisciplinary scientists study both neural circuitry and behavior to understand the processes of the brain. However, this does not mean that they study parts of the brain, then study some behaviors, and understand the system. It also does not mean that they take a top-down approach (brain to behavior) or bottom-up approach (behavior to brain) — the choice here should depend on the specific research question. Interdisciplinary scientists study both brain and behavior at the same time. By studying both at the same time they can see how behavior emerges from neural circuitry and how neural circuitry emerges from behavior. The two are dependent on one another, they are not separate.

Consider this optical illusion:

optical-illusion-face-and-candlestick

If I just look at the picture on the left, I might only see a chalice and begin describing all of its visual properties and then infer its function. However, if I look at the picture on the right then it might become apparent that the picture is both a chalice and two people looking at each other. If I have too narrow of a focus — only studying the chalice — then I completely miss understanding that this is an optical illusion. Understanding the whole is important, and one part is not the greater than the other.

However, as mentioned earlier when trying to identify the function of an elephant’s ear, if I do not have a starting point for inferring function or mechanism then I could be asking the wrong questions. This is the point that the authors in the original scientific publication also make. If you do not study the behavior of the animal or process that you are interested in, then you will be asking all the wrong questions concerning neural circuitry. One cannot understand the game of chess by just analyzing all the pieces and the board. You must first observe how the game is played, and then you can determine what makes the pieces and the board important.

This is example of watching chess being played first and then analyzing the pieces and the board, represents a top-down approach. However, as already mentioned, the approach you take is particular to the question you are interested in. Different approaches give you different answers. And in the unknown world of brain and behavior, we may really not know enough to properly infer how something functions.

Regardless, this example of chess also applies to all experiments using animal models. For example, I might have learned how to play chess on a large and heavy wooden board with specially molded iron pieces. And as long as I understand the rules and processes of chess, then I can play chess on any board — be it big or small, plastic or wood, physical or virtual. But if I spend all my time studying the chess pieces and never watching how the game is played, then it might be difficult for me to identify which chess piece does what on a different chess set. Just like it would be difficult for me to determine which brain areas of a mouse might be analogous to which brain areas in a human without measuring behavior.

The authors also explain that multiple neural circuits may be responsible for a single behavior, and a single neural circuit may be responsible for multiple behaviors. This further complicates the issue of studying one part of the animal over the other. Thus, one specific neural circuit does not map to one specific behavior.

neural-activity-in-animals-and-the-behaviours-associated

In conclusion, the neuroscientists who published the original scientific article are correct: behavior is necessary and you must study it if you want to understand the brain. However, all the fancy techniques neuroscientists have developed, independent of behavior, help us ask specific questions about neural circuitry and about behavior. Also, all scientists experimenting on animals —not just neuroscientists — should understand the arguments used in this paper and apply it to their own experiments. This will help us better understand how findings in one species might relate to findings in another, and thus help the translation of all science using animal models.

Justin Varholick

Nonhuman primate research gives us otherwise impossible treatments

stuart-bakerLast week, Dr. Stuart Baker, a Professor of Movement Neuroscience at Newcastle University, wrote an article in The Conversation detailing not only the lifesaving research that nonhuman primates contribute to, but also the exceptional care they receive while contributing to human health. Stuart last week also published a paper describing his laboratory’s development of a new device that helps stroke patients to recover, a device that was dependent on development first in rhesus monkeys.  In his piece in The Conversation, Baker highlights the following:

  • Why it is important to understand how the brain controls movement
  • Why nonhuman primates are superior to other animal models for this type of research
  • The state-of-the-art care his laboratory primates receive

Why it is important to understand how the brain controls movement

“We typically take the ability to move in a fluid, coordinated way for granted,” Baker writes. Yet many adults “suffer damage to the brain’s pathways for movement, for example after a stroke. Suddenly, everyday tasks become a tiring, frustrating struggle.” Baker studies how the brain controls movement in order to understand the connections between our brains and our limbs. By understanding how brain cells adapt their neuronal activity during movements, how neurons are connected, and how they reconfigure after injury, Baker can then develop devices for therapeutic treatment like the one he published about in The Journal of Neuroscience last week.

Why nonhuman primates are superior to other animal models for this type of research

In his article in The Conversation, Baker emphasized the need for nonhuman primates in movement neuroscience research. In order to understand the deepest inner workings of the brain – those that don’t contribute to scalp recordings, which can be used in humans – one must probe deeper than the surface. Baker uses an analogy of an airport: “When we record from the scalp, we average the signals from many millions of cells. It’s a bit like placing a microphone on the ceiling of an airport departure hall, and measuring the sound levels.” This type of information is useful because it can tell you “what times of the day the airport is busy.” But “some aspects of the airport’s operations – those outside on the tarmac – would be missed.” Similarly, Baker says, some brain centers that control movement are so deep beneath the skull that a deeper exploration beyond scalp recordings is required. Enter monkey models: “Many pathways for movement control are different between primates such as humans and other animals such as rats. Only a primate model can give us information which is relevant to human diseases.

One of Newcastle’s macaque monkeys. Newcastle University, Photo credit: S. Baker

One of Newcastle’s macaque monkeys. Newcastle University, Photo credit: S. Baker

The state-of-the-art care his laboratory primates receive

Stuart is well aware that there are inaccurate and baseless claims that his lab animals suffer. In The Conversation, he describes in detail the care his monkey receive, from positive reinforcement training so that they learn to perform complex tasks with their hands or arm to undergoing surgery “in a fully equipped operating theatre, with sophisticated anaesthetics and painkilling medication borrowed from state-of-the-art human care.” The monkeys are carefully monitored to ensure they are not distressed or in pain.

Baker also emphasizes the “huge effort [that] goes into minimizing suffering every day.” This effort is not optional, but “an integral part of what we do and who we are.”

Baker’s article is a wonderful example of the type of transparency that scientists should engage in more frequently. Without such candor, the public is unaware of the extent to which animal models contribute to lifesaving therapeutics – and also of the excellent care they receive from the people who truly love working with them.

What can you share about your research and the animals you work with?

Scientific community unites in defence of primate research

The Backstory

It’s been a busy few weeks for those who wish to explain the role of primates in research. Last week the NIH held a workshop on “Ensuring the Continued Responsible Oversight of Research with Non-Human Primates” (watch it back here). The Congressionally mandated workshop resulted from report language that was associated with a PETA campaign. PETA hoped the workshop would question whether primates should be used in research at all. Instead PETA were disappointed when many experts came together to talk about how primates remained important to medical and scientific research. Days before the event, PETA activist, Professor John Gluck, wrote to the New York Times to criticise the use of primates in research. Speaking of Research posted a response – “The ethics and value of responsible animal research” – that was signed by over 100 scientists. Other organisations have subsequently written back to the newspaper with letters published this week.

Over in the UK, a group of 21 academics (primarily anthropologists) including Sir David Attenborough (notable broadcaster and naturalist) wrote to the online-only Independent newspaper to call for an end to certain neuroscience experiments involving primates. This provoked a backlash from the research community, who accused him of being “seduced by pseudoscience“. They may have had a point – Attenborough’s letter,  organised by Cruelty Free International, backed itself up with a recent paper “Non-human primates in neuroscience research: The case against its scientific necessity” (authored by two staff at Cruelty Free International). The UK Expert Group for Non-Human Primate Neuroscience Research told The Independent:

“We are disappointed to see that David Attenborough and a number of scientists have been misled by the pseudoscience in the paper by CFI, an organisation intent on ending research with all animals, not just primates. “

The paper (by Bailey & Taylor, 2016) itself suggests that several medical advances – such as Deep Brain Stimulation – did not rely on animal studies. This would not seem to match what can be seen in the academic literature, indeed Alim Benabid, who won a Lasker Award for his role in developing the technique noted the important role of animal models, including primates.

Researchers Unite!

There are many other events which have played into a frustration by primate researchers, but the response was huge. Understanding Animal Research coordinated a letter on the role of primates in research. Within a few days hundreds of primate researchers and neuroscientists had signed up. Notable signatories included: Sir John Gurdon, who won the 2012 Nobel Prize in Physiology or Medicine, and the 2009 Albert Lasker Basic Medical Research Award, for their work in reprogramming mature cells into early stem cells; Sir John E Walker, who won the 1997 Nobel Prize in Chemistry for elucidating the mechanisms behind the synthesis of ATP; Professor Mahlon DeLong and Alim Benabid, who jointly won the 2014 Lasker-DeBakey Clinical Medical Research Award for their research developing Deep Brain Stimulation as a surgical treatment for Parkinson’s (the same discovery that the Bailey & Taylor, 2016, paper suggested did not require  primates); and Professor Miguel Nicolelis, whose Walk Again project allowed a young paraplegic in an exo-skeleton to kick a football.

neuroscience-starsOver twenty organisations, including Speaking of Research, the Society for Neuroscience (SFN), and the American Psychological Association (APA) signed their support ( a full list of signatories can be found here). The letter was published by the UK newspaper, The Guardian, on 13th September (and the following day in print), along with an accompanying article.

Furthermore, around 400 researchers also signed on to the letter:

Nonhuman primates have long played a key role in life-changing medical advances. A recent white paper by nine scientific societies in the US produced a list of fifty medical advances from the last fifty years made possible through studies on nonhuman primates. These included: treatments for leprosy, HIV and Parkinson’s; the MMR and hepatitis B vaccines; and earlier diagnosis and better treatment for polycystic ovary syndrome and breast cancer.

The biological similarities between humans and other primates means that they are sometimes the only effective model for complex neurodegenerative diseases such as Parkinson’s. More than ten million people suffer from Parkinson’s worldwide, and a recent study estimated that one in three people born in 2015 will develop dementia in their lifetime. Primate research offers treatments, and hope for future treatments, to patients and their families. Already over two hundred thousand Parkinson’s patients have had their life dramatically improved thanks to Deep Brain Stimulation surgery, which reduces the tremors of sufferers. This treatment was developed from research carried out in a few hundred monkeys in the 1980-90s.

Given that primates are intelligent and sensitive animals, such research requires a higher level of ethical justification. The scientific community continues to work together to minimise the suffering of primates wherever possible. We welcome the worldwide effort to Replace, Refine and Reduce the use of primates in research.

We, the undersigned, believe that if we are to effectively combat the scourge of neurodegenerative and other crippling diseases, we will require the careful and considered use of nonhuman primates. Stringent regulations across the developed world exist to ensure that primates are only used where there is no other available model – be that the use of a mouse or a non-animal alternative and to protect the wellbeing of those animals still required. The use of primates is not undertaken lightly, however, while not all primate research results in a new treatment, it nonetheless plays a role in developing both the basic and applied knowledge that is crucial for medical advances.

A segment of the letter printed in the Guardian

A segment of the letter printed in the Guardian

Get involved – show your support!

While, the letter itself is published. Understanding Animal Research are continuing the accept signatories from neuroscientists and primate researchers (signatories must be from academia and must hold a PhD, MD or equivalent). These are being updated on a regular basis on their website.

So if you wish to sign – click here: https://www.surveymonkey.co.uk/r/PrimateLetter

Already they are up to over 550 signatories – just one week after they started collecting (considerably more than the 21 signatories that Cruelty Free International managed in their letter, and with a lot more expertise in the area of Neuroscience).

Speaking of Research

Teaching Children about the Brain

Stacey BedwellDr Stacey A Bedwell is a postdoctoral researcher at Nottingham Trent University, whose work focuses on the prefrontal cortex of the mammalian brain. Dr Bedwell has previously written a guest post about the importance of animals in neuroscience for us.

Stacey recent published a children’s book, How does my brain work, which takes readers through a little girl’s journey through the different areas of the brain, and how they work.  We asked her some questions.

Why did you decide to write this book?

I wanted to create something to engage young children in neuroscience, specifically I wanted to create a publication that could make a complex area of study accessible to young minds. I decided upon the format of a picture book to do this so that the book could have an engaging and easy to follow narrative. I created characters within the book in order to convey the content in a fun and exciting way.

How do you think animal research should be discussed with children?

Research using animals should be openly discussed with children. I think a lot of children grow up unaware of the contribution that scientific research using animals has made to advances in medicine and other areas of biology. I think it is important to acknowledge in textbooks, other non-fiction books, TV shows and in classrooms the significance of animals in certain aspects of research. This applies both to current research and to past discoveries.

Page from 'How Does My Brain Work?'

Page from ‘How Does My Brain Work?’

What tips do you have when discussing animal research with younger audiences?

I think it is necessary to educate children about the uses of animals in research from multiple perspectives. In my opinion the best approach is to give children all of the facts, about why animal research takes place, what animals are used for and how, as well as what the alternative methodologies are.

How else do you think scientists should engage younger audiences?

It is important to make all areas of science accessible to children, to inspire the next generation of researchers and clinicians. In order to engage young audiences it is essential for scientists to communicate their ideas and knowledge outside of academic journals.

Dr. Stacey A. Bedwell, author of ‘How does my brain work?

Guest Post: The Importance of Animals in Neuroscience Research

Our guest post today is from Dr. Stacey A Bedwell, a postdoctoral researcher at Nottingham Trent University, whose work focuses in the prefrontal cortex of the mammalian brain. In this post she discusses her work with rats, and why it is important for neuroscience. If you are interested in writing a guest post for us, please contact us today.

My research interests are in brain connectivity, studying how the billions of neurons in the human brain are connected and how their complex organisation allows us to carry out high order functions such as forward planning and decision making. I am specifically interested in the most frontal part of the mammalian brain, the prefrontal cortex. This region is known to be involved in complex processes such as decision making, forward planning and social inhibition – the behavioral restraint a person has in social situations.

Why study the prefrontal cortex?

It is not always clear to people outside of the area why basic research like mine is important for medical science in the long term and how it will indirectly benefit us as humans (and also often benefit animals). A lot of people don’t realise that a lot of work needs to be done to provide the knowledge that is required before exciting new drugs and treatments are developed. For instance, the development of treatment for spinal cord injury has been built upon an increased knowledge the underlying structure. In my area of neuroscience research it is really important to develop a clear picture of the underlying anatomy and organisation before we can improve our understanding of how the prefrontal cortex as a region functions, and ultimately lead to a better understanding of prefrontal associated neurological deficits that will help us to develop improved treatments and prevention strategies.

animal testing, animal research, vivisection, animal experiment

The prefrontal region has been associated with a range of neurological deficits including schizophrenia, depression and autism. Autism in particular is thought to involve abnormalities in prefrontal connectivity. We cannot begin to fully understand how these functions work and how deficits come about until we gain a clearer understanding of the structure and organisation of the neuro-typical prefrontal cortex, beginning with the underlying anatomical circuitry. My research for the past few years has focussed on revealing the complex neuronal circuitry that comprises this fascinating brain region.

Why do I use rats in my research?

People often ask me why I used animals in my research, whether it was necessary and why I couldn’t use another non-invasive approach in human subjects such as MRI. My most frequent observation, particularly from non-scientists, is that it is hard to see the importance of research using animals, if like mine, it doesn’t focus on a specific disease or produce findings that will lead immediately to the development of a new drug or therapy..

The optimum method for investigating brain connections is to physically visualise them, and the best method for visualising brain connections is the use of neuroanatomical tract tracers, fluorescent molecules, taken up by neuronal cells, that enable us to map pathways and the connections between brain regions. There are several different tract-tracing methods available, but I use fluorescent tracers injected into the prefrontal cortex in rats. With the use of a fluorescent microscope it is possible to visualise neuronal connections down to individual cells, something which we are far from being able to do with non-invasive imaging in humans. Being able to visualise and analyse the 3 dimensional location of connections on such a systematic and fine scale has allowed us to reveal properties of prefrontal cortex connectivity which had previously been undescribed (Bedwell et al 2015 & 2014). Our most prominent and surprising finding is that of non-reciprocal connections in PFC pathways, which is inconsistent with our knowledge of cortical organisation from other complex brain regions – cortical connections have long been assumed to be largely reciprocal in nature. This shows that PFC is organised very differently to other brain regions. These novel organisational properties provide an important basis on which to build a clearer understanding of how this complex region of the brain is organised and offer an insight into how and why the prefrontal cortex is able to carry out complex processes.

What happens to the rats?

I used rats in all of my experiments. The rats were all obtained from a Home Office licensedbreeding facility in the UK and were acclimatised to their new environment for a couple of weeks before they were used in any experiments to reduce their stress. Our rats were housed in groups of at least two and were kept in climate controlled specialist cages – they were very comfortable. There are strict Home Office guidelines in the UK as to how rats used in experiments are kept and cared for to ensure their welfare needs are met, this applies to before, during and after experiments and they are followed to the letter. A lot of effort goes into ensuring no animal suffers as part of an experiment.

Image from Understanding Animal Research

Image from Understanding Animal Research

My experiments required the rats to undergo surgery so that the tracers could be injected directly into the brain at a very precise location. This was always carried out to a very high standard. We received advice from a vet, who also sat in on the first few surgeries to ensure we were performing the procedure in accordance with regulations. The surgery always involved a team of at least three people and the welfare of the rat was the greatest priority. This included the correct use of anaesthesia, analgesics pre and post operatively, as well as continued behavioural observation in order to identify any post-operative complications before they could cause suffering to the rat. At the end of the experiment each rat was euthanised and the brain removed for microscopic analysis of the labelled connections.

What next?

I am now developing studies of cortical function and functional connectivity, that can be carried out on human participants with non-invasive methodologies such as transcranial magnetic stimulation (TMS) and electroencephalography (EEG), and will complement the earlier studies undertaken in rats. Unfortunately, the technology is not yet available to investigate fine scale anatomy in such a non-invasive manor, so both animal and human studies are required in order to understand how the underlying brain structure relates to function. Until such techniques are developed, animal experiments will continue to be vital for the continued progress in neuroscience, as it is in so many areas of medical science.

Dr Stacey A. Bedwell

Students in Rome to rally for Prof Caminiti and future of science in Italy

Tomorrow students at the Sapienza University of Rome – Italy’s largest University – will join their Professors and members of the campaign group Pro-Test Italia outside the Department of Physiology and Pharmacology to show solidarity with Professor Roberto Caminiti, a leading neurophysiologist whose work is being attacked by animal rights extremists.

Tomorrow Pro-Test Italia will return to the streets of Rome, joining students and scientists in support of crucial research.

Tomorrow Pro-Test Italia will return to the streets of Rome, joining students and scientists in support of crucial research.

As with many recent instances of anti-scientific populism in Italy, the campaign against Prof. Caminiti began in earnest with a dishonest broadcast on the Italian tabloid TV news programme Striscia la Notizia which misrepresented the work being done by Pr0f. Caminiti and his colleagues. Prof. Caminiti responded to these false allegations in a video which you can watch here (in Italian with English subtitles)

Following the broadcast the European Animal rights Party (PAE) announced that they would be holding a demonstration Sapienza University of Rome, on February 5 2015, with the declared will to “free” the monkeys that are used by Pr0f. Caminiti and his colleagues. This has sparked concerns that the PAE – and the more extreme animal rights groups who will no doubt accompany them – will attempt to repeat the events of 20th April 2013, when five animal rights activists forced entry into the Pharmacology Department of the University of Milan, stealing hundreds of mice and destroying years of research.

There is, however, a major difference between 2013 and today; today scientists and students are ready to stand up and  defend their research. A group of neurobiology students at the Sapienza University of Rome have organized a counter-demonstration (see this Facebook event for details) tomorrow morning – February 5 – to show support for Prof Caminiti, defend their department, and speak up for the future of scientific research in Italy.

On Monday their stand received a boost when Professor Vincenzo Vullo, Head of the Faculty of Pharmacy and Medicine at Sapienza University of Rome, circulated an email to all scientists, staff and students to express support for Prof. Caminiti, and called on them to join him in defense of the research being undertaken at the Department of Physiology and Pharmacology:

Dear colleagues, dear students,

I transmit an open letter by Prof. Roberto Caminiti in defense of the unacceptable smear campaign underway against the scientific activity of the Laboratory of Behavioral Neurophysiology, Department of Physiology and Pharmacology of our University.

In this regard, I wish to emphasize the scientific value of Prof. Caminiti, an internationally acclaimed researcher whose research has made a significant contribution to the knowledge of the central nervous mechanisms of motor control. I also want to remember especially his human qualities, demonstrated in the constant respect and care with which he always treated animals necessary for his studies.

In expressing my personal solidarity with Prof. Caminiti, I ask for the support of all members of the faculty in defense of the scientific research conducted at the Laboratory of Behavioral Neurophysiology of our university.

Vincenzo Vullo”

The email also included a letter addressed to all staff and students from Prof. Caminiti:

Dear Colleagues, dear Students,
On December 18 2014 the TV show “Striscia la Notizia”, using images illegally shot in our animal facilities, broadcast a report with the aim of stirring in the public opinion a campaign condemning the scientific activity of the Neurophysiology of Behaviour Laboratory, in the Department of Physiology and Pharmacology of our Atenaeum, where other professors and I carry out our scientific activity, which started in the year1985.
To reply to the accusation of animal cruelty, as an act of absolute transparency of research towards the public, I posted online a reasoned reply, in which it is showed and commented on everything that is performed in our laboratories, thanks to several projects financed by MIUR (Italian Government research funder- Speaking of Research) and the EU, and according to experimental protocols regularly authorized by the Ministry of Health.
On January 23 2015, once again “Striscia la Notizia” returned to the topic, using the images we put online, to claim, with the help of a “flora and fauna” specialist (!) that our studies were useless and cruel, where it is unanimously recognized in the scientific community that our research, together with other work carried out in a select group of international laboratories, lead to the development of brain-computer interface in humans and to the cerebral control of artificial prostetics in patients with paralysis due to neurodegenerative or neurovascular diseases, just like similar researches lead to the development of deep brain stimulation in the treatment of Parkinson’s disease.
Exploiting the footage broadcasted by “Striscia la Notizia”, the European Animal rights Party (PAE) launched a national demonstration, set to take place on February 5 2015, in front of our Department, with the declared will to “free” the animals that we are working with, and together with the Antivivisection League (LAV) stated that they have submitted a complaint to the Prosecutor’s Office in Rome, to open an investigation aimed to the confiscation of the animals, and to open a criminal case against me for animal cruelty.
I call on you, confident that you believe in a country guided by reason, commitment and study, and not driven by obscurantism, just like the “Stamina” case, that you all well know (for more on the Stamina scandal see this recent report -Speaking of Research) . And I ask yo to defend, with the appropriate instruments, the scientific activity and the dignity of a Department of our Atenaeum.
On the morning of February 5, wearing a white lab coat and flower in the buttonhole, I will be in front of my Department to defend and reaffirm that ideal that drove us all to become MDs and researchers.
With best regards,
Roberto Caminiti

We congratulate both faculty and students at Sapienza University of Rome for taking this action in support of science, and wish them, Pro-Test Italia, and all friends of medical progress every success as they stand together in this noble cause.

Speaking of Research