Meek no more: turning mice into predators

A recent study published in the journal Cell, has shown that  switching on a particular group of neurons in the mouse brain can turn these otherwise timid creatures into aggressive predators. Why would anyone want to do this you might ask? After all, with the tumultuous political events of 2016, do we really want to add killer mice to our worries? Thankfully, the researchers aren’t planning to take over the world one rodent at a time, instead they want to understand how the brain coordinates the complex motor patterns associated with hunting.

During the evolution of vertebrates, the morphology of the head changed to allow for an articulated jaw. This is a more scientific way of describing the type of jaw most of us are familiar with: an opposable bone at the entrance of the mouth that can be used to grasp and manipulate food. This anatomical change allowed for the development of active hunting strategies and the associated neural networks to coordinate such behaviours. The researchers wanted to identify which parts of the brain contain the networks for critical hunting behaviours such as prey pursuit and biting. They began by looking at an evolutionarily old part of the brain known as the amygdala, specifically the central nucleus of the amygdala (CeA), because this area has been shown to increase its activity during hunting and has connections to parts of the brainstem controlling the head and face.

In order to study this part of the brain, the authors used a technique called optogenetics. This technique involves introducing the gene for a light sensitive ion channel into specific neurons. It is then possible  to ‘switch on’ the neurons (i.e. cause them to fire bursts of electrical activity) simply by shining blue light onto them. This is what the researchers did with the neurons in the CeA.

To begin with the researchers wanted to find out what happens when you simply switch on the these neurons. To test this they put small moving toys, resembling crickets, into the cage as ‘artificial prey’ and watched the animals’ behaviour. The mice were largely indifferent to these non-edible ‘prey’, however as soon as the light was switched on the mice adopted a characteristic hunting position, seized the toys, and bit them. This never occurred when light was off. The scientists also tested the mice with live crickets (i.e. prey that mice would naturally hunt). When using live prey the mice (without the light activation) hunted as normal. However, when the light was switched on the researcher saw that the time needed for the mice to capture and subdue their prey was much shorter and any captured crickets were immediately eaten. The combination of these results suggests that stimulation of the central nucleus of the amygdala (CeA) not only mimicked natural hunting but increased the predatory behaviour of these mice.

One question that might spring to mind from this study is: How do we know that these mice are really hunting? Perhaps the light had unintended effects such as making the mice particularly aggressive or maybe very hungry? After all, both explanations could account for the increased biting of non-edible objects and the faster, more aggressive cricket hunting. To argue against increased aggression levels, the authors point out that CeA stimulation did not provoke more attacks on other mice – something you might expect of an overly aggressive mouse. So what about increased hunger? The scientists in this study also think this is unlikely because they allowed the mice access to food pellets and found no difference in how many pellets were consuming during the time the laser was on versus the time the laser was off.

So how is hunting behaviour controlled by the CeA? The hunting behaviour displayed by mice can be divided into two aspects: locomotion (prey pursuit and capture) and the coordination of craniofacial muscles for the delivery of a killing bite. The scientists hypothesised that the CeA may mediate these two different types of behaviour through connections with different parts of the brain. The two key brain regions investigated in this study were the parvocellular region of the reticular formation in the brainstem (PCRt) and a region of the midbrain called the periaqueductal grey (PAG).

By using optogenetics the researchers were able to selectively stimulate the CeA to PCRt projection and found that this caused the mice to display feeding behaviours. Interestingly, stimulating this pathway seemed to only elicit the motor aspects of eating e.g. chewing rather than increasing the mice’s hunger. Conversely, disrupting the function of this pathway interfered with the mice’s ability to eat. Taking this into a ‘live’ setting, the mice could still pursue their prey and subdue it using their forepaws, but they struggled to deliver a killing bite. The researchers then turned their attention to the pathway between the CeA and the PAG. They found that stimulating this projection caused mice to start hunting more quickly, pursue their prey faster, and hunt for longer. Unlike the experiment above, stimulating this pathway had no effect on feeding-type behaviours. Now the scientists geared up for the big experiment: they’ve shown that stimulating the CeA leads to predatory hunting. They’ve shown that biting and pursuit seem to be controlled by different pathways from the CeA. So they decided to see if activating both pathways simultaneously (CeA to PCRt and CeA to PAG) could mimic the effects of stimulating the CeA itself. Indeed, they found that stimulating these two pathways together led the mice to robustly initiate attacks on artificial prey.

So what can we learn from this study? The scientists have demonstrated that the CeA acts as a command system for co-ordinating key behaviours for efficient hunting via two independent pathways. However, there are still some key questions remaining, for example, what determines whether the CeA sends those commands? The scientists hypothesise that cues such as the sight or smell of prey might cause the CeA to respond and send the command to elicit the appropriate motor actions. However, they can’t prove this in the current study.

Despite these limitations, this paper is a great example of how scientists can use cutting edge tools, like optogenetics, to tease apart the brain pathways responsible for different aspects of a complex behaviour such as hunting.

Post by: Michaela Loft

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Video astronomy: an update

Early last year I posted an article discussing the merits of webcam imaging. I had just bought some new equipment and wanted to put my enthusiasm into blog form. I was getting fed up with the annoying short observing time our cloudy nights provide us in the UK. Traditional long exposure photography, used to capture faint galaxies and nebulae, is simply out of the question on all but the clearest of nights. However, webcam astronomy is easy to learn, cheap and quick enough to do between clouds. Not only this but, on Moonlit nights when long exposure photography would produce washed out pictures of galaxies, webcam imaging can deliver great Lunar landscapes. Also, during the day, a webcam coupled with a telescope can capture the ever-changing surface of the Sun, meaning you can do astronomy without losing sleep!

So it is now time to show you some of my attempts at webcam astronomy. Before I show any processed images I first want to demonstrate the main limitation facing astrophotography (other than light pollution); atmospheric turbulence. In image 1, a section of the Moon is being videoed; notice how the detail is constantly shifting in and out of focus. This distortion is caused by currents of air at different temperatures which bend and scatter the light passing through the atmosphere.

Image 1. A movie clip of craters Aristoteles (top left) and Eudoxus (top right). The image shimmers because of the constant turbulence in Earth’s atmosphere. Author’s own work.

Although this may look bad, atmospheric distortion can get far worse! For instance, if the Moon moves close to the horizon then light coming from its surface has to travel through far more air, which badly distorts and scatters this light. Just look at how distorted the Sun looks as it is setting. Atmospheric distortion can also be caused in other ways. In image 2, the Moon was passing just above my house, which unfortunately is not well insulated. This atmospheric distortion caused by hot air escaping from my house dramatically reduces the detail you can see – I’d ask my wife to keep the heating off while I’m imaging but I fear this wouldn’t go down too well.

Image 2. Another movie clip taken when the Moon was setting just above my house. The hot air causes increased turbulence that causes the detail of the lunar landscape to dance and blur. Author’s own work.

Luckily webcam astronomy possesses one amazing advantage over other forms of photography. Unlike traditional long exposure astrophotography, video recordings produces thousands of individual images (or frames) of your target, this means you can be very strict about which frames to keep and which to discard. For example, to get one high quality image, I take about 4 minutes of video containing 14400 frames at 60 frames/sec. I then pick the best 2000 of these frames and, using a program called Pipp, I can stack them together to reduce noise and improve detail (see previous post about stacking). This procedure means I can remove all the frames that were distorted by the atmosphere.

So after all that processing what am I left with? The answer is superior detail, better than any individual frame in the movie or even images taken using long exposure photography. In Image 3, Lunar detail as small as 1Km across can be seen, since the Moon was 370000Km away at that point, this resolution is equivalent to spotting a 2cm wide 1p coin from 7.4Km away! Quite an achievement for my small telescope. All because I have used only the frames taken during atmospheric stillness.

Image 3. A stacked image taken using the best 2000 frames of the movie (Figure 1). The resolution has now improved substantially. Author’s own work.

Even during strong atmospheric turbulence, reasonable detail can be retrieved, in Image 4, Lunar craters as small as about 5 Km can be seen, not as good as in Image 3 but still impressive.

Image 4. The stacked image from the movie shown in Image 2. Despite the strong atmospheric disturbance, fine detail can still be resolved. The crater to the far left is Sacrobosco. Author’s own work.

Of course webcam astronomy is not limited to the Moon. With the correct light rejecting filters, you can turn this powerful technique onto the Sun. During July 2016 there was a fantastic chain of Sunspots (see Image 5), these features change shape every day: merging, splitting and distorting providing a very dynamic and unique astronomical sight.
Of course before undertaking solar photography a few considerations must be addressed. (1) Make sure you research how to observe/image the Sun safely, I will not be happy if you go out and blind yourself after reading this article. (2) Be aware that the Sun will heat up your telescope creating turbulent air inside the tube, to avoid this problem I covered my scope in kitchen foil.

Image 5. A stacked image of sunspots taken on 19/07/2016. The internal structure of the Sunspots can be seen as well as individual granulations across the solar surface. Author’s own work.

The planets are probably the most popular and evocative telescopic targets of all. Thankfully webcam imaging provides an easy way to image them and make your own Solar system collections! I’ve added my own incomplete collection in Figure 6. The sizes the planets appear are to scale.

Image 6. My Solar System collection: Jupiter (top left), Uranus (top middle), Neptune (top right), Mars (bottom left) and Venus (bottom middle). Author’s own work.

For the planets, I used exactly the same method as with the Moon. The hardest part is finding the planets in the night sky. If you are unfamiliar with night sky then their locations can be found using planetarium software like Stellarium. I must also mention that you will need some experience finding Uranus and Neptune, they are faint and you will need to be able to use a finder scope to home in on these planets.

In conclusion, I started learning astrophotography in the wrong order, webcam astronomy provides all the excitement of capturing a new world in your back garden but without the long nights, tiresome setup and ruinously expensive equipment.  So fetch that old scope out of your garage, buy a webcam and get recording I have evidence to show you wont be disappointed.

Post by: Daniel Elijah.

Carfentanil: The next step in the opioid crisis?

The US is in the midst of a national opioid epidemic. The use of opioids, which includes prescription drugs and heroin, has quadrupled since 1999. The Centres for Disease Control and Prevention (CDC) has confirmed that these drugs now kill more people than car accidents in the US, making it the most common form of preventable death.

Opioids are a class of opium-derived compounds that relieve pain. These drugs use the same receptors as endorphins, eliciting analgesic effects by inhibiting the release of neurotransmitters in the spinal cord. Exploited for centuries, they are still considered one of the most efficacious treatments for pain, despite serious side effects including physical and psychological addiction.

Fentanyl, a synthetic opioid developed for use in surgery, was first linked with overdose deaths in 2005 . Alarmingly, the number of overdose cases involving fentanyl have escalated in recent years, with its misuse regularly making the headlines due the sheer number of deaths associated with this drug. High profile cases, such as the death of the global star Prince have only added to this.

Carfentanil, another drug with a similar structure to fentanyl, has recently exploded onto the scene as carfentanil-laced drugs rear their toxic heads. An analogue of fentanyl, carfentanyl was first synthesised in the US in 1974 by Janssen Pharmaceutica (owned by Johnson & Johnson). This opiate was designed for use as a general anaesthetic in large animals such as rhinos – just 2mg of carfentanil can knock out an African elephant. Due to its extreme potency the lethal dose range of this drug is unknown in humans, which greatly amplifies the risk involved in taking the drug.  Carfentanil is 10,000 times more potent than morphine, and 100 times more potent than fentanyl. As with other opioids, carfentanil causes death by respiratory distress or cardiac arrest, leading to death within minutes.

So, why are these drugs being increasingly abused? One explanation is that prescription of opioid drugs have increased since the 1970s – this being the result of a series of papers published downplaying the risk of addiction associated with use of opioid painkillers such as oxycontin and fentanyl. They were marketed to doctors as wonder drugs for treating day-to-day pain, with little addiction potential. As we now know, this turned out not to be the case. The resulting willingness of doctors to prescribe opioid painkillers increased the availability of these drugs. This problem was in turn worsened by a subset of pharmacies illegally filling out multiple prescriptions and the phenomenon of ‘doctor shopping’, where patients obtain prescriptions from multiple doctors at once. Currently, over 650,000 new opioid prescriptions are dispensed every day in the US by doctors.

A number of recent studies found that almost half of young people using heroin had abused prescription opioids beforehand. This comes as no surprise when such potent drugs are used routinely to treat even minor sports injuries in young people. As a result of this alarming trend, new regulations were implemented in the US in 2014 to attempt to restrict the misuse of prescription painkillers. Unfortunately, this has forced many people experiencing drug addiction to turn to prescription fraud and illegally produced pills. Cartels in Mexico, the primary supplier of heroin to the US, have stepped in to provide cheaper and more potent opiate alternatives. Evidently, the reduction in the availability of legally-produced drugs has failed to remedy the issue of opioid misuse.

The unknown quantity and composition of the drugs bought on the street, combined with the recent explosion in recreational use, has led to a surge in accidental overdoses. In 2016, both fentanyl and carfentanil have been found as additives in heroin, cocaine and counterfeit Xanax pills in Florida, Ohio and neighbouring Michigan (including Detroit) among other states. Like any other illicit drug, users have no way of determining the strength or purity of what they have bought to any degree of accuracy.

The latest spike in overdoses has led to the DEA issuing a public health warning, with the Acting Administrator Chuck Rosenberg describing carfentanil as ‘crazy dangerous’ . It is hard to put a figure on the number of cases involving carfentanil as there are issues with obtaining samples and identifying how much was taken, with some facilities also unable to identify the compound in toxicology reports at post mortems.
The opioid antagonist naloxone (sold as Narcan™ nasal spray) also struggles to reverse the effects of fentanyl and carfentanil, with reports of patients needing up to five times the recommended amount of naloxone for a heroin overdose. As a result it can take up to five minutes to revive a patient, an effect that normally takes a matter of seconds, vastly increasing the chance of lasting brain damage and death.

On average, opioid overdoses kill 91 Americans every day. This disturbing figure will continue to rise unless rapid change is seen in both government policy and in society as a whole. There remains no easy solution to opioid problem, and with a single gram of carfentanil able to cause 50,000 fatal overdoses, it seems the situation will only worsen unless dramatic changes are put into effect. Continued research into addiction causes and treatments, coupled with investigation into new medications to treat pain are also necessary for long-term management of this devastating crisis.

Post by: Sarah Lambert

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Why the rat pack don’t do drugs

From awkward school seminars to the topical banter of South Park, we’ve all heard the message loud and clear ‘Drugs are bad….ok?’. And yes, as a rule messing with your brain chemistry is probably not a great idea. But, there are certain nuances surrounding drug use and addiction that you may not be aware of and which could have important implications for how we understand addiction and work with addicts.

Many of us may have heard about studies in the 1960’s involving lab rats and cocaine. In these relatively simplistic studies researchers offered caged rats a choice between regular drinking water and water laced with cocaine. Most animals studied didn’t just favour the drug-laced drinking water, they actively drank so much they eventually killed themselves. These shocking findings lead many researchers and politicians to believe that drugs such as heroine and cocaine were so dangerously addictive that they caused individuals to loose control over their own behaviour. And yes, these drugs can certainly be dangerous however, there was more to this story than these researchers realised.

In the 1970’s Bruce Alexander, a curious psychologist from Vancouver, noticed a big problem with this research. He recognised that all the rats studied in these addiction experiments were housed in small wire cages with no access to any of the things that make a wild rat’s life worth living (i.e. space to explore, a network of furry friends and lovers and things to play with). So Alexander re-ran these early experiments but with one important difference, his rats all lived in the lap of rodent luxury. These lucky rats were residents of Alexander’s Rat Park, where they had space to explore, tunnels to scamper through and friends to interact with. Amazingly, although the residents of Rat Park were curious enough to try drug-laced drinking water, most would then shun this water – consuming less than a quarter of the drugs isolated rats used; and, most importantly, none of Alexander’s rats died from overdoses.

On top of these findings Alexander also discovered that isolated and addicted rats which were subsequently released from their enforced isolation and introduced into Rat Park soon gave up their destructive habits in favour of a normal life.

So how does this change our understanding of addiction?

Professor Alexander argued that his discovery showed that addiction was more than simply a disease which chemically hijacked the brain, instead it could be an adaptation to an individual’s environment and social situation – i.e. addiction is not about you, it’s all about your cage.

In favour of Alexander’s ‘Rat Park theory’ we know that, although following an injury many individuals are prescribed the pain killer diamorphine (a medical name for heroin), we rarely have problems with these patients becoming addicts. Could this be because the patients are able to return home after their stay in hospital to loving supportive families and rewarding careers so no-longer need to rely on these drugs?

Although these finding are compelling and perhaps suggest useful social interventions with regard to treating addicts, it is still important to understand the limitations of the Rat Park and Alexander’s theory. Indeed, it is important to recognise that ‘Rat Park’ oversimplifies a complex societal and biological problem and that this oversimplification may not be beneficial. Research still suggests that certain people have a physical predisposition towards addiction and, despite living socially enriched lives, these individuals can still fall fowl to the addiction cycle. The myriad of research into the biological substrates of addiction could make-up a post in it’s own right, so I will attempt to cover this in more detail in a later article. However, for now it’s important to recognise that even though environment is likely to play a role in addictive behaviours, biology is also important in shaping our vulnerability to addictive drugs and our subsequent success in kicking the habits. This research should all be considered together if we really want to successfully tackle the problems raised by drugs in our society.

Post by: Sarah Fox

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The Adventures of Cornish Cod in the land of Scousers

Over two years ago I began a University course in Liverpool, having traveled across the Pennines from the glorious lands of Yorkshire my accent stood out while I also found the scouse accent particularly confusing – especially when drunk (student life). But it’s not just students living far from home who are getting confused. Climate change has been warming our oceans so much that cold water species have started to migrate further North. This means that the Cornish Cod are now visiting Liverpudlion waters. It’s the start of a real North/South aquatic mixer! We all recognise the differences in culture between the North and South of England but it’s also likely that these differences appear in fish culture, especially regional accents. I know aquatic accents may sound a bit fishy but this is a real phenomenon.

Cod attract a mate by making sounds, a highly specialised ‘sonic muscle’ is drummed against the swim bladder to produce a thumping sound. But, as the Cornish cod and the Scouse cod start to mingle, the differences in their ‘accents’ could actually prevent them from communicating. Reminds me of on a night out in Liverpool when the native guys try to chat you up – can anyone understand them or are the chat up lines just so bad that you’re really better off not understanding?

Males produce sounds (back to Cod now in case anyone was confused) which stimulates females to release their eggs, this allows the males to synchronise when they release their sperm to fertilise the eggs. If the fish aren’t able to understand each other it could seriously damage their reproductive success. Even if Cornish Cod and Scouse Cod can set aside their differences and develop an understanding, there is still the issue of noise pollution.

Noise pollution in an area can drown out sweet mating sounds of male cod. Boats being driven past spawning grounds could have serious effects on the cod communication. It could be that the species manages to adapt over time to overcome this dilemma (similarly to how we over act our gestures when the music is too loud for you to ask your mates if they want a drink). Perhaps the male cod will develop some epic dance moves to seduce their lady friends, or they may have to start signalling louder to be heard. This would however require more energy, meaning the Cod would need to hunt more often which could have detrimental effects on the rest of the ecosystem.

Poor Scouse Cod not only do they have to cope with noise pollution but now they are being invaded by Southerners! Could life get any worse for them? Let’s just hope there isn’t a boom in the fish and chip shop trade…

Post by: Jennifer Rasal

References:

http://www.telegraph.co.uk/news/2016/10/04/cod-speak-with-regional-accents-scientists-believe/

https://commons.wikimedia.org/wiki/File:Portrait_of_Cod.jpg

http://www.bbc.co.uk/news/science-environment-37557945

http://www.fishecology.org/soniferous/waquoitposter.htm

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