Category Archives: Science news

Shark Diary, Episode III: The oldest living vertebrate

The Greenland shark’s scientific name is Somniosus microcephaly, which means ‘sleepy small brain’.  They live in the cold waters of the North Atlantic and Arctic Oceans, and are members of the family Somniosidae – the Sleeper Sharks. This name implies their slow growth and low levels of activity. In some ways they live up to their name, but in many other ways they are anything but sleepy, small-brained creatures!

Native range of the Greenland shark. Source: FishBase

How old is old? 

These sharks were known by Greenlanders to grow slowly and the fact that they can reach lengths of 5.5 metres implied they may also be very old. It wasn’t until a few years ago that a Danish team led by Prof John Steffensen was able to confirm their extreme longevity, and publish the findings last year in the journal Science.

Shark face2

Calculating the age of a cartilaginous shark is more complicated than it is for a bony fish. This is because bony fish have otoliths, bones of the inner ear which grow in rings, much like that of a tree. By counting the rings of the otolith, you can determine the fish’s age. Cartilaginous fish like sharks (and rays) do not have otoliths, nor do they have any other true bones.

To overcome this challenge, John and his team used carbon dating techniques to determine the age of 28 female sharks (81 to 502 cm total length) collected during expeditions to Greenland between 2010 and 2013. Carbon dating is famously used to determine the age of fossils, but they used this same technique on the carbon in lenses in the sharks’ eyes. This carbon comes from the  “bomb-pulse” that entered the ecosystem following the nuclear tests of the 1950s. The carbon in body parts formed during that time is in a different form.

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From these sharks, growth curves were established linking a shark’s age to its size. Using these, we can now calculate the age of live sharks from their measurements, which we took on the expedition. Current estimates suggest that the average Greenland shark grows less than one cm per year. That makes animals longer than 5 metres between 275 and 510 years old!

How does living so long affect the shark’s bodies?

Aging is decay, at least in humans. Indeed, the biggest risk factor for a large number of diseases like heart disease and cancer is advancing age. So how is it that the Greenland shark can live for so long?

At the moment, we know very little. Very early evidence from previous work suggests these sharks do not have any special strategies for surviving damage from free radicals. Another health concern specific to top oceanic predators is accumulation of toxic substances in their bodies. However, recent work on accumulation of organic pollutants does not suggest that they accumulate with age in the Greenland Shark either. We hope to learn much more about how these sharks age as we process the samples from our expedition. For instance, Takuji Noda, Bob Shadwick and Diego Bernal are studying movement and skeletal muscle function in sharks of different ages. This could tell us whether Greenland sharks deal with frailty, another plague of human aging.

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Most sharks caught have this parasite hanging from their eye.

Some aspects of a shark’s long life bear no comparison to humans. Although dimming eyesight might feel like an inevitable part of aging to us, Greenland sharks contract a parasite on their cornea, so they may need more than a pair of reading glasses as they age! A 4-6 cm long crustacean dangling from the centre of a shark’s eye is off-putting, but also intriguing. It raises obvious questions about how the parasite affects vision and how the fish survives with potential vision-impairment. General consensus is that the parasite severely impairs the ability of the eye to form images, but how important is vision in animals living 1 kilometer below the surface? Perhaps they rely more on their other senses, like smell. In any case, gut contents show these sharks eat everything from small fish to whole seals, suggesting they forage successfully even with a large crustacean dangling from their eye!

Conserving this old shark 

The Greenland shark is slow-growing and thus also slow to reach reproductive age. A member of our team on the expedition, PhD student Julius Nielsen, from the University of Copenhagen has been trying to understand how body length relates to reproductive maturity in both males and female sharks. Their current estimate is that females reach sexual maturity at lengths of over 400 cm, which makes them at least 150 years old. Males, who are smaller than the females, may reach reproductive maturity at slightly shorter lengths.

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Ovaries and uteri recovered from an injured female shark humanely euthanised during the expedition. Watch Julius talk you through them, and what he hopes to learn from tracking shark’s movements after their release, below.

This slow maturation means it takes at least 150 years for shark pups to start reproducing! This has big implications for the population, and for conservation. Indeed, the Greenland shark population may still be recovering from being over-fished before World War II, when their livers were used for machine oil. Calculating back from the amount of machine oil produced suggests that between 50,000 and 150,000 animals were caught per year between 1900 and 1938. Prices of shark-liver oil fell in 1949 as other options became viable, and the fishery then collapsed. Hatchlings born to parents who were caught for their livers are now teenagers and still not quite at reproductive age. That may be the reason why there are very few reports of juvenile Greenland sharks.

Slow growth leading to late reproductive maturity is a big factor for conservation strategies in this animal. At present, the Greenland shark is a common by-catch, meaning it’s unintentionally caught along with other fish, in the North Atlantic and Arctic Oceans. This suggests that its population is still quite strong. But as it takes so long to increase the population of adult animals, they are vulnerable to increased fishing pressure in a warming Arctic environment. Thus they are listed as near-threatened on the ICUN list and there is a growing need to understand their physiology, life history and their role as top predator in the Arctic marine ecosystem.

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The tag on this shark will transmit data via satellite about where it goes after being released.

Follow #SharkDiary on Twitter to see all the updates about the expedition.


This expedition was made possible by funding from the Danish Centre for Marine Research, the Greenland Institute of Natural Resources, The Danish Natural Science Research Council and the Carlsberg Foundation.

Shark Diary, Episode II: Meet the team

The main goal of our Greenland shark research mission was to gather physiological and biological information about the sharks. We tagged every shark we caught with an identification tag, in case they were caught in the future. We measured body and fin length in all sharks and took a small sample of tissue from each animal for DNA analysis. To further our understanding of how these sharks use their environment, we tagged some with satellite bio-loggers, which track their location as they move about in the depths. We also wanted to understand more about the way they swim – as Greenland sharks are considered among the slowest swimmers in the sea.  We employed a different kind of tag for this called an accelerometry tag.

Some of the sharks were injured on the line – either by being bitten by other Greenland sharks or by swallowing hooks. These sharks were humanely euthanized and brought aboard the vessel so that we could study their internal anatomy. We studied the reproductive organs of both male and female sharks. We also studied their skeletal muscle to link how the muscles contract with their slow swimming speed.  Lastly, we wanted to study their hearts and blood circulation. We wanted to learn about heart rate, about blood pressure about how the heart muscle contracts and how much blood it pumps, and about blood chemistry.

John Fleng Steffensen, University of Copenhagen

The Greenland Shark first caught my attention back in 2001 when the captain of our research vessel told me he’d heard that the creatures live to be very old. When I searched for past research on this creature, I only found one reference to their age, from back in the 1960s, when P.M. Hansen found that one shark had grown only 8 cm in 16 years. Such slow growth seemed to suggest they might live very long. It was our work in finding a way to calculate the age of these sharks that eventually determined that they could indeed live for centuries! Our cruises to southwestern Greenland have taught us much more than just the sharks’ longevity: on our latest mission, we looked at heart muscles, properties of the circulatory system (heart rate and blood pressure), where and how fast they swim, and filming their feeding at depths of 200 to 600 meters.

Takuji Noda, The Institute of Statistical Mathematics

I am an interdisciplinary scientist working between biology and informatics. My main interests are locomotion, behaviour and physiology of fish in their natural environment and how to measure that information in various types and sizes of fish. Therefore, I am developing customized animal-attached data loggers, composed of a variety of sensors (the technique is called bio-logging). With colleagues, I have established a company called Biologging Solutions Inc. to support the creation of customized data loggers and solutions for improving data recovery.

I am interested in the swimming ability and behaviour of Greenland sharks, which live in deep and cold waters. In the fjord of Greenland during the expedition, we attached multiple-sensor data loggers to Greenland sharks. The loggers automatically detached from the sharks and popped up to the surface of the water, where we could find and recover them using radio telemetry. Using a high-resolution accelerometer and speedometer, we measured swimming patterns such as tail-beat frequency and speed to understand how slowly they move and if they exhibit bursting movement when feeding.

Although it was difficult to measure bursting moment during the recording period, the data showed the sharks generally swims at very slow tail-beat frequency (at about 6 seconds per beat). This supports the measurements from physiological experiments in the lab.

Julius Nielsen, University of Copenhagen

I am a PhD student from the University of Copenhagen and have been working on the #GreenlandSharkProject since 2012. This project investigates many aspects of the biology of Greenland sharks including longevity, feeding ecology, migration patterns and population genetics.

I first started studying sharks caught as bycatch by the Greenland Institute of Natural Resources during fish monitoring surveys. These sharks gave unique insights into this poorly studied species, for example revealing their extreme longevity. The oldest shark we analysed was at least 272 years old, making the Greenland shark the longest-living vertebrate known. We also learned that they catch fast-swimming prey like Atlantic cod and seals, an unexpected finding given their seemingly sluggish nature. How they do this is still a mystery; I expect they might be ambush predators, who catch prey by being stealthy rather than speedy, as well as opportunistic feeders, scavenging carcasses from the ocean floor.

On this expedition, my main focus is to deploy satellite tags on the sharks to learn more about their movement patterns. We especially want to tag sexually mature animals to learn about mating areas and pupping grounds. I will also take samples from any sharks too injured to release, to inform my ongoing investigations about feeding, longevity, and reproductive biology.

John, Peter, Diego and Emil

L-R: John Steffensen, Peter Bushnell, Diego Bernal and Emil Christensen aboard the research vessel.

Diego Bernal, University of Massachusetts Dartmouth

I’m a comparative physiologist who studies how temperature affects the swimming muscles of fish who are elite swimmers. These quick fish, such as the tuna and mako shark, keep their bodies warm. The Greenland shark is the opposite of the fish I usually study, it’s slow and cold. I was curious to learn how its muscles function in its cold environment and how it manages to catch its prey. On our last expedition to study these sharks, the equipment we brought to study the muscles was too small for the huge muscle fibres. We also learned that we needed a way to keep the samples at 1-2 degrees Celsius, to mimic the water temperature where the sharks live.

Peter G Bushnell, Indiana University South Bend

I am a comparative physiologist: I’m interested in how different animals adapt their bodily functions to meet their needs. I focus on the circulatory and respiratory systems of marine animals, and have been studying polar animals in the Arctic and Antarctic for more than 25 years. When my colleague John Steffensen and I discovered how little was known about Greenland sharks, we decided to look at various aspects of their biology such as their swimming ability, migratory movements, diet, metabolism, and reproduction.

On this particular trip I was interested in how their hearts work, as this will impact their cardiovascular system, metabolism, and swimming ability. To do that, I cut out little strips of heart muscle and stretched them between clips. Every time a strip was stimulated by a small electric current, as happens in a normal heart to cause it to beat, the strip would briefly contract (shorten) and then relax: this is called a twitch. By measuring various aspects of the twitch, like strength and duration, we can learn a lot about how the heart might operate in an intact animal.

Making this technique work in Greenland sharks proved very challenging. However, I have managed to conclude that a twitch takes about 3-5 seconds, putting maximum heart rate somewhere between 12-20 beats/min. To put that in perspective, your normal resting heart rate is about 60-70 beats a minute with a maximum heart rate around 180 beats/min. Heart function is temperature sensitive, so it is not surprising that Greenland sharks swimming in very cold and deep water have much lower heart rates. However, I believe their heart contracts very slowly, which is in keeping with the idea that they don’t do anything quickly.

Robert Shadwick, University of British Columbia

I am a physiologist who studies animal form and function, also known as biomechanics. I am interested in the structure and mechanics of the heart and blood vessels in a variety of animals. Blood pressure is an important indicator in an animal. In fish, it reflects the level of activity of a species. Tuna for example are fast, continuous swimmers and have relatively high blood pressure compared to slower fish such as carps.

Activity levels vary greatly among shark species. The Greenland shark is generally considered very sluggish, but may swim fast to capture and eat seals. The purpose of my study was to estimate average blood pressure in the Greenland shark, to understand how these large sharks compare to other species.

To do this, we used the aorta, a large blood vessel that carries blood to the gills. The aorta is very elastic at low blood pressure, but when blood pressure is high the aorta wall becomes stiff. This transition between elastic and stiff typically occurs around the average blood pressure of the animal. By measuring the flexibility of Greenland shark aortas at different pressures, we can estimate the average blood pressure of these animals.

Our preliminary results show that the Greenland shark aorta is very flexible at pressures below 3 kilopascals (kPa, a measurement of pressure), but becomes very stiff with further increase in pressure. Therefore, we can tentatively estimate the average blood pressure to be around 2-3kPa. Our own blood pressure, in comparison, is about five times more (13 kPa), and the slow-moving dogfish shark’s is 4kPa. These results support the idea that Greenland sharks are indeed a sluggish and likely a slow-moving species.

the team in Narsaq, Captial of south Greenland

The team enjoy an evening on land in Narsaq, south Greenland. L-R: Julius Nielsen, Takuji Noda, Bob Shadwick, John Steffensen, Diego Bernal, Peter Bushnell.

Holly Shiels, University of Manchester

As a fish cardiovascular scientist I am interested in the mechanisms that maintain or adjust heart function in a changing environment. Such knowledge has application to cardiac health and disease and in predicting how organisms, populations, ecosystems and natural resources respond to environmental change and stressors.

Investigating cardiovascular function in the Greenland shark is very exciting, because these animals are long-lived and thrive in cold environments.  Several of their cardiac features make them particularly interesting. The first is their very slow heartbeat. Although not surprising for an animal living at 1-2⁰C, it takes a long time for their hearts to fill with blood between one beat and the next. This affects how much the heart stretches out and how strongly it then contracts to push out the blood. We suspect stretch regulation of force is particularly important in this shark.

We are also interested in the Greenland shark’s longevity.  In humans, age is associated with many cardiovascular problems, such as fibrosis (the aged heart becoming stiffer). A key question for us is whether the Greenland shark heart stiffens with age. And if it does, how does that affect its ability to fill will large blood volumes between heart beats?

Both stretch and fibrosis of the heart muscle create an environment for arrhythmia – irregular heart-beats.  Arrhythmias are dangerous in humans, but what about sharks?

During the expedition, we used echocardiography to measure heart rate before releasing the sharks. In animals too injured to release, we collected the hearts and measured pressure and flow relationships. We then preserved the hearts to study their structure, including fibrosis, in the lab.

Emil Aputsiaq Flindt Christensen, University of Copenhagen

I am a biologist with special interest in the interaction between ecology and physiology, the so-called ecophysiology, of fishes. I work both in the field, fitting animals with tags to study their behavior in the wild, and in the lab studying physiology through both animal behavior and biochemical analyses of tissues.

My research has focused a lot on the salt and water balance in fish. In that regard, sharks and similar species are “osmo-conformers”, meaning that they maintain water balance by producing organic molecules such as urea and a chemical called TMAO.

TMAO is an especially interesting compound to me, because it stabilizes chemical reactions that happen in the body, which is helpful under the high pressure conditions found in the deep sea. Thus, analyzing TMAO levels in the Greenland shark might tell us something about how deep it swims.

On a side note, Greenlandic hunters feed their dogs with Greenland shark, but sometimes the dogs get poisoned. This might be because TMAO degrades to a poisonous compound called TMA.

Follow #SharkDiary on Twitter to see all the updates about the expedition.


This expedition was made possible by funding from the Danish Centre for Marine Research, the Greenland Institute of Natural Resources, The Danish Natural Science Research Council and the Carlsberg Foundation.

Shark Diary, Episode I: On the trails of the Greenland shark

By Holly Shiels, University of Manchester

The Greenland shark was one of the lesser-known species of sharks up until last year when their extreme longevity was uncovered. The finding that they live in the deep, dark Arctic waters for hundreds of years captured the imagination of the world and the attention of scientists. How does an animal born in Shakespeare’s time still patrol the deep today? What do they eat? When do they breed? What features distinguish males from females?

There are many open questions about these enigmatic animals.  The purpose of our #GreenlandSharkProject expedition was to use physiology – the science of how living things work – to help us find answers.

The Greenland shark can live for over 400 years.

The Greenland shark is listed by the International Union for Conservation of Nature (IUCN) as data-deficient and near-threatened. While we know the species is under pressure to survive, we need more information about its biology to form an effective conservation plan.

To gather this information, John Fleng Steffensen, Professor in Fish Physiology at the University of Copenhagen, brought together an international group of eight physiologists. Our team included experts in swimming and locomotion (kinematics), skeletal muscle and cardiac muscle, osmoregulation (the regulation of water, salt and other ions in the body) and eco-physiology (how an organism’s body adapts to its environment).

Researchers Diego Bernal, Bob Shadwick and Takuji Noda aboard the ship.

In the broadest sense, our mission was to gather data on the physiology of these mysterious animals – their hearts, their movements, their diet, and their reproduction. We were also interested in whether their body’s adaptation to cold water is related to their longevity. Clarifying how the Greenland sharks age without developing diseases associated with human ageing, like cancer and heart disease, could lead to new therapies down the line. Not only can we find clues about aging and disease, but also, understanding shark physiology is important for their conservation.

1,856 miles from Manchester to Nuuk

Before boarding the ocean-going research vessel to spend two weeks off the coast of southern Greenland, we gather in Nuuk, Greenland’s capital. The journey from Manchester to the world’s largest Island proves to be an adventure in itself.

After a hectic day in the lab in Manchester, I head to the airport for my flight to Copenhagen. I’m travelling light: a hoodie, woolen socks and the rest of the bag filled with electronics, glassware, and chemicals to make up the 15 kilograms I’m allowed to carry. A few weeks ago, I sent three large boxes of equipment and clothes to be put on a cargo ship to Nuuk.

Fast forward to a few hours later. I’ve reached my hotel in Copenhagen and head out on the town for some Danish beer with three of the other scientists, as our flight to Nuuk isn’t until the morning. Drinking now is important, as the research vessel is dry. Too much heavy equipment on the rough sea to have alcohol blurring judgement!

When I arrive back to my hotel room, I remember that I’ll need to keep my scientific chemicals cool during the night. There’s no fridge in my room, so out the window suspended on a string they go. It’s about 5 degrees Celsius outside so they should be fine, as long as there are no mischievous Danish squirrels about.

The team prepares to board the Dash-8 to Nuuk.

By the morning, two more team members have arrived. The five of us board our Greenland Air flight to Kangerlussuaq, Greenland. The plan is to connect there on a small plane to Nuuk, where we will join the rest of the team. The weather, however, has different plans. A large and unseasonal snowstorm is brewing above Nuuk.

Our small Dash-8 tries to find a clearing in the snow that will let us land. After circling and circling, we attempt a landing twice but the wind and snow are fierce. The pilot has no other choice but to abort. The altimeter shows that one of our landing attempts brings us just 110 metres above the runway! Finally, the captain comes over the radio with the bad news that we need to head back to Kangerlussuaq. We are running out of fuel and there was no sign of the storm lifting. This is a problem, as our ship is meant to be leaving Nuuk that night.

Luckily, the storm eventually lets up and we are able to join the rest of the team at the ship. In the end, our departure is pushed back to the next morning because of a radar issue. This gives us a final restful night at the dock before the adventure at sea!

The team finally reaches the snow-covered research ship.

Follow #SharkDiary on Twitter to see all the updates about the expedition.


This expedition was made possible by funding from the Danish Centre for Marine Research, the Greenland Institute of Natural Resources, The Danish Natural Science Research Council and the Carlsberg Foundation.

Running away from stress…literally

By Molly Campbell, University of Leeds, @mollyrcampbell

Exercise – for some, it’s a hobby, for others, a burden. We all know exercise is good for us. Yet, ironically, many people feel too busy or stressed to exercise regularly. Particularly during exam time, who wants to swap an hour of revision for an hour of tiring yourself out?

Research actually suggests that committing to exercise when you are experiencing stress can lower your stress response both now, and in the future. Regular exercise can be particularly helpful in boosting your mood, and thus your motivation to do work. Scientific research suggests that exercise elevates molecules in the body associated with the feeling of joy, whilst decreasing those that cause stress.

Post-exercise feelings of bliss

The term ‘runner’s high’ was coined in the 1970’s following an apparent worldwide increase in the number of people running long distance. This feeling of elation was attributed to the increased levels of endorphins in runners’ blood after exercise. Since then, many studies have been conducted that expand on this work to clarify exactly how exercise produces this ‘feel good’ effect.

Exercise also increases the release of endocannabinoids in the body. These are a type of cannabinoid that are endogenous, meaning they are made within our body. Endocannabinoids serve as a message between cells. Cells receive the message when the endocannabinoid attaches to another molecule, called a receptor, on the outside of a receiver cell. The receiver cells for endocannabinoids are in the central nervous system (brain and spinal cord) as well as other parts of the body. This elicits a wide range of beneficial effects.

The chemical anandamide, one type of endocannabinoid, gets its name from the Sanskrit word ‘ananda’ meaning joy. It is created in areas of the brain involved in motivation, memory, and higher cognitive function. Whilst its exact function has not been clarified, increased levels of anandamide are associated with states of heightened happiness. Anandamide can enter the brain through the so-called blood-brain barrier. This means that an increase of anandamide in the blood is followed by an increase of the chemical in the brain.

An experiment by Elsa Heyman and her colleagues demonstrated that, following a period of intense exercise, cyclists have increased levels of anandamide in their blood (1). This increase in anandamide was correlated with the increase of a molecule that is extremely important for the growth and maintenance of neurons in the brain, called brain-derived neurotrophic factor (BDNF).

Johannes Fuss and his colleagues used mouse models to demonstrate that exercising on a running wheel produced a significant increase in anandamide levels, which was correlated with a substantial reduction in anxious behaviours (2). When the researchers gave the mice a drug to block the cannabinoid receptors, to which anandamide binds, this reduction in anxiety was reversed.

Together, these findings therefore suggest an emerging role for the endocannabinoid system in producing the feeling of well-being and stress relief people experience after exercise. However, anandamide is broken down in the body very rapidly, possibly explaining why exercise is most beneficial when done regularly.

Sweat away your stress

Susanne Droste and her colleagues investigated the short-term effects of exercise on stress hormones in mice (3). Adult male mice were provided access to a running wheel for four weeks before undergoing a series of behavioural tests. Exercising mice were found to exhibit a significant decrease in corticosterone (the equivalent of the stress hormone, cortisol, in rodents) responses to a novel environment compared to control animals that had not exercised. These animals were also found to be less anxious in behavioural tests.

Researchers have also found long-term changes in the stress response after repeated exercise. Mindfulness experts suggest exercise, such as running or yoga, can indeed be a meditation practice carried out ‘on the go’. By placing focus on the repetitive movement of our joints and the increase in our heart rate, and the general effects exercise exerts on our body, we are distracted from the thoughts circling through our mind. Repeatedly applying this focus, particularly when high levels of stress cause us to be entangled in our thoughts, can produce long-term changes in the bodily tools we rely on to calm down. Ann Kennedy and her colleagues found that several studies show that this improves breathing rate and depth, lowers heart rate, and increases our ‘rest and digest’ response, or the so-called parasympathetic nervous system (4).

Although it may seem a chore to take time out of the day to get your body in motion, research about our physiology suggests that your brain (and therefore your grades) will benefit from doing so!

References:

  1. Heyman, E. Gamelin, F.X., Goekint, M., Piscitelli, F., Roelands, B., Leclair, E., Di Marzo, V. and Meeusen, R. 2012. Intense exercise increases circulating endocannabinoid and BDNF levels in humans—possible implications for reward and depression. 37(6), pp. 844-851.
  2. Fuss, J. Steinle, J., Bindila, L., Auer, M., Kirchherr, H., Lutz, B. and Gass, P. Runners high depends on cannabinoid receptors in mice. PNAS. 112(42).
  3. Droste, S.K., Gesing, A., Ulbricht, S., Muller, M.B., Linthorst, A.C and Reul, J.M. 2003. Effects of long-term voluntary exercise on the mouse hypothalamic-pituitary-adrenocortical axis. Endocrinology. 144(7), pp. 3012-3023.
  4. Kennedy, A. and Resnick, P. 2015. Mindfulness and Physical Activity. American Journal of Lifestyle Medicine. 9(13), pp. 221-223.

 

The Glastonbury of Neuroscience

By Anjanette Harris, University of Edinburgh, @anjiefitch

I have been to many music festivals in my time, but last month I went to my first Neuroscience Festival. Every two years, the British Neuroscience Association holds the Festival of Neuroscience, which boasts a jam-packed program of research talks from experts across many disciplines within neuroscience, as well as workshops and discussion forums. It is quite simply the national celebration of neuroscience.

Last month, nestled amongst the canals of Birmingham, the International Conference Center provided the perfect backdrop for over 1500 scientists from around the world to get together, share their latest data, and enthuse one another. This year, The Physiological Society hosted a strand running through the festival called The Neurobiology of Stress as part of their annual theme Making Sense of Stress. One of the symposia, organised by Professor Megan Holmes, brought together researchers from around the world, including myself, to present our work on imaging the emotional brain.

What puts us at risk of depression?

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Dr Stella Chan, a lecturer in clinical psychology from the University of Edinburgh, kicked off with the staggering statistic that half of all cases of depression first occur in adolescence. Stella reminded us that adolescence is a tricky time in which teenagers struggle with intense emotions on the road to self-discovery. But why do some youngsters develop depression while others don’t?

To answer this question, Stella studies how young people perceive themselves and the world around them. One startling finding is that those at risk of depression find it harder to see joy in other people’s faces. Because Stella uses teenagers at risk of, but not yet suffering from, depression she is able to see if there are changes in perception that may flag up that a youngster is likely to develop depression. If Stella can untangle whether a negative self-opinion is the cause or consequence of depression, she may be able to develop mind-training techniques to prevent depression in those at risk.

Untangling cause and effect using mice

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Dr Marloes Henckens, a post-doctoral researcher from the Donders Institute at Radboud University, presented her work on the effects of stress on brain function. She uses both human and mouse subjects to help her distinguish between cause and effect. Marloes began by setting her work in context; she highlighted that the brain is a collection of networks and that brain disorders are probably caused by disorders of the connections between different networks.

With that in mind, Marloes showed that stressing humans or giving them stress hormones caused the connections that make up the fear network to become stronger. While this is useful for priming a person to tackle danger, it may lead to an anxiety disorder, such as post traumatic stress disorder (PTSD) in which suffers are haunted by intense unpleasant memories. Marloes takes pictures of the brains of mice with PTSD-like symptoms and has shown that reduced activity at the front of the brain (important for reducing unpleasant memories) is a consequence and not the cause of PTSD. It remains to be seen how connections between different networks are affected in mice with PTSD.

Hormonal influences on brain activity in rats
awake

The following speaker, Professor Craig Ferris of Northeastern University, is the pioneer of imaging rats’ brains while they are awake. Craig began with a whistle-stop tour of the groundbreaking technology that he and his team have developed. His special scanning technology allows researchers to monitor brain activity while the rats are responding to things. For example, Craig showed changes in brain activity in mother rats as their pups start to suckle. It comes as no surprise that the brain areas involved in reward and motivation are active with breast-feeding. In fact, in these rats, breast-feeding is more rewarding than cocaine!

Craig then presented images of brain activity involved in aggression. To observe this, he first took pictures of the brain of a male rat that was happily lying in the scanner with its girlfriend, and then introduced an unfamiliar male rat and observed the changes in the first rat’s brain. The abrupt change in brain activity that was seen in the male rat’s brain might be described as blind rage, as it is similar to that observed with the onset of a seizure. Craig’s ambition knows no bounds: he finished his talk with musing on whether he could fit a killer whale into his brain scanner!

The impact of stress on emotional memory in rats

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The final speaker was me, Dr Anjanette Harris. I’m a post-doctoral researcher from the laboratory of Megan Holmes at the University of Edinburgh. I want to understand how stress affects brain function. This is particularly tricky to study in humans, especially if we want to look at the effects of early life stress on the brain, so we use rats (read more on the importance of using rodents in psychiatric research in my previous blog post). The work that I presented uses the technology of Craig Ferris coupled with memory exercises for rats that we specialize in designing. We have shown that rats that experience stress in early life form stronger memories of unpleasant experiences. These rats also have stronger activity in brain areas involved in fear when recalling unpleasant experiences in adulthood. This mirrors what is found in humans and means that we may be able to test potential therapies for human memory disorders on rats, ensuring that the treatments target appropriate areas in the brain.

Challenges and importance of studying depression in rodent models

By Anjanette Harris, University of Edinburgh, @anjiefitch

Sufferers of Major Depressive Disorder (MDD) are more than just a little ‘down in the dumps’. Persistent low mood and low self-esteem are classic symptoms, but sufferers also experience learned helplessness, increased anxiety, feelings of guilt and worthlessness, and enjoy the pleasures of life less (also called anhedonia).

To investigate potential therapies and the cause of this debilitating disease, it is sometimes necessary turn to animal models, such as rats and mice. Rats and mice offer a powerful tool to investigate the causes and consequences of mood disorders, because unlike in humans, we can control stressors, genetics, and environmental factors more easily in rats and mice. We can give certain drugs, implement exercise regimens, and modify diets to see what happens.shutterstock_106507433

While a rat or mouse cannot communicate its feelings, we can measure some aspects of depressive behaviour. Rodents normally love sugary water, but when they are anhedonic they have a weaker preference for it. A forced swim test involves placing a rodent in a container of water in which they can swim but not escape. Choosing to float rather than tread water during this test is used as a sign of depression.

Measuring preference for sugar and floating behaviour in rodents is similar to a questionnaire in a human study.  While a questionnaire identifies depressed subjects, it reveals very little about the cause of depression. To successfully treat or prevent MDD, we need to understand what goes wrong in the brain.

In humans, a specific type of brain scan called functional magnetic resonance imaging (fMRI) helps bridge the gap between identifying and unpicking what is faulty in a depressed brain. This scan measures oxygen levels in the brain’s blood circulation. Since active brain cells use more oxygen, the fMRI signal indicates the parts of the brain that are working hard.Capture

We can use these scans to look at differences between the brain activity of depressed and healthy people. For example, in response to negative stimuli such as pictures of sad faces, the outer layer of the brain (the cortex) exerts weaker control over the emotional centre (the limbic system) in depressed patients. In addition, networks in the brain that respond to reward are increasingly less active as anhedonia becomes more severe. These findings may help explain why those who are vulnerable to MDD are both unable to supress negative mood when it arises and no longer enjoy previously pleasurable experiences.

While manipulating rodent genomes and administering drugs or stressors is straightforward, neuroimaging is more challenging. We have specially built small scanners, but a key to successful imaging is a still and calm subject. One solution is to anaesthetise the rats or mice.  However, since anaesthesia is rarely used in human imaging and a sleeping rodent cannot participate in cognitive tasks, this limits our ability to look at cognitive processing in rats and mice in the same way that we do in humans.

In recent years, researchers have developed ways to gradually acclimate rats or mice to being held still in an fMRI scanner. To study cognitive processes, scientists can use tasks that can be completed in the MRI scanner. For example, they train rats to associate visual or olfactory stimuli –such as a flashing light or a vanilla scent-  with a foot shock. They then image their brains while presenting the flashing light or scent.

This technique is an improvement on the classical test for fear in rodents, ‘freezing behaviour’. When a mouse or rat is afraid, it freezes like a statue. Using brain scans translates better to humans than studying freezing behaviour. For example, researchers used the visual task set-up to show that rats that experienced early life stress, have enhanced activity in brain networks that process fear. Early life stress is a known risk factor for anxiety and depression in humans.

Reward, emotional regulation, extinction learning (learning to forget an unpleasant memory), and cognitive bias (whether we perceive ambiguous situations to be positive or negative) are aspects of depression that we can currently assess in humans. The next big challenge is to devise behavioural tasks that enable us to examine these in awake rodents while their brains are being scanned.

This way we can validate rodent models of depression, elucidate what’s happening in the brain during negative affective state, and guide the development of successful treatments for Major Depressive Disorder.