Monday, April 13, 2015

A week of tame foxes

“You're checked all the way through to... some place I can't pronounce,” said the woman who was checking me in at my small local airport in Illinois.

Novosibirsk. It is the third largest city in Russia, located in south-western Siberia. It is the location of the Novosibirsk State University, one of the best universities in Russia, where the Institute of Cytology and Genetics maintains Belyaev’s tame foxes.

(You may already know about the fox domestication project, but if you don’t, Wikipedia has a good primer, and Jason Goldman has written about them.)

The Institute is actually in Academic City (Akademgorodok), a suburb of Novosibirsk. Academic City is an odd blend of the European — my hotel would not have been out of place in France — and the Russian, with its thick stands of birch and fir. During my early April visit, there was still three or four feet of packed snow on the ground, and mud season was commencing as the temperature rose.

The Institute is in a green-roofed building shoulder-by-shoulder with other university institutes. The farm, where the foxes live, is a ten or fifteen minute drive out of the city. I went to the farm daily to study the socialization period in tame and aggressive fox kits.

Tame fox kit (silver color)

I was working with these kits at three weeks of age, before they were old enough to start venturing out of the nest and interacting with the world. At this point they shouldn’t yet have entered their socialization period. Yet you could already tell the difference between the tame kits and the aggressive kits. Kits within a group weren’t identical in behavior: some complained about being restrained, some yelled, some fell asleep, some were calm and silent. However, the aggressive foxes tended to make more noise, and the tame foxes tended to be more curious about their surroundings. Two aggressive fox kits tried to bite. One tame kit did.

As for the adults, I found more behavioral variation than I’d expected there as well, although the head of the laboratory where I work had warned me again and again that the foxes vary sigificantly in behavior. Tame foxes were curious and wanted to interact with us, but some were shy, diving into their nest boxes or to the far side of their cage and then returning slowly. One fox stretched his body out, low to the ground, so that he could sniff my companion’s face without having to commit himself to coming too close. (When I offered to let him sniff my face, he stole my hat and then carried it around his cage while the neighboring foxes watched in fascination.)

Slightly shy tame fox (Georgian white color)

Other tame foxes could not contain their enthusiasm at having people to interact with. They rolled on their backs and made excited yipping noises and wagged their tails. In their joy, they would hold our hands gently in their mouths, something I saw again and again with them but that I have very rarely seen a dog do.

Fox holding my hand in his mouth (platinum color)

I visited foxes from the control line, who had not been bred for behavior. They were simply afraid of us: when their cage door was opened, they retreated. If cornered, they would bite, but any aggression they showed was entirely defensive.

I also saw foxes from the line that has been selected for aggression to humans. Some of them were afraid and aggressed only defensively. Some were more scary, coming forward to the front of the cage to bite again and again. Certainly they were afraid of humans, but something in their brains or hormones makes them more proactive and less passive in their defensive aggression.

Finally, I met rats and mink selected for tameness or aggression. The tame rat that I met was happy to be held and happy to interact with me, but I don’t have enough experience with pet rats to say if this was unusual. The aggressive rat that I met was terrifying, hurling herself at a gloved hand when her cage door was opened and screaming repeatedly, even after we backed off.

The tame mink were less curious than the tame foxes and didn’t seek interaction with humans in the same way. One let himself be held by his keeper but I wasn't allowed to touch him, in case he might try to bite.

Tame mink

Notice the little white patch on his chin — more white coloration is associated with more tameness in both minks and foxes. Another, all-white mink was tamer and I could pet him. He seemed deeply passive, not seeking interaction, just tolerating it.

Tame white mink

Remember that part of the tame fox story — that as the foxes were selected for tame behavior, they started showing characteristics typical of domesticated species, including white patches and curled tails? Only a small percentage of the tame animals have these features, but I saw several piebald fox kits:

Piebald fox kit (silver color)

...and my host kindly pointed out one fox with a gorgeous example of a curled tail.

Fox with curled tail

What an amazing week. I kept thinking: how strangely my life has turned out!

Wednesday, March 25, 2015

Who funds dog research?

As I move through my training and think ahead to my future career, I wonder: who will pay for all this research I want to do on dogs? I have so many questions to ask!
  • What changes happen in the canine brain as it enters, and then leaves, the socialization period?
  • How is the brain of a fearful dog different from that of a confident dog?
  • What are the genetic differences behind these variations?
  • How do environmental differences (prenatal stress, early learning, adult life) change the brain?
In other words, what are the mechanisms in the brain that differ in fearful dogs — receptors, neurotransmitters, synaptic wiring? And how can I learn about them without using invasive (painful and/or terminal) techniques?

Who are the caretakers of Dog, the species, who care about fearfulness? We as dog owners and lovers care, but dog owners and lovers aren’t the ones who are trained to heal unhealthy dogs, to perform research aimed at understanding them, and we (mostly) aren’t the ones who breed them. So who are the groups who are the caretakers of Dog, and what subsets of Dog do they care for?

Image: Who is my caretaker?


We (I am a veterinarian) are trained to heal sick dogs. Relatively few veterinarians perform research compared to those who engage solely in clinical practice. But some do perform research: most commonly as faculty at veterinary schools alongside a clinical practice, or less commonly as researchers without a clinical practice at research instititutions.

Veterinary research, as a result of this strong emphasis on healing the unhealthy, is focused on clinical results. Veterinarians most commonly perform research which asks questions about the effectiveness of particular techniques — medications, surgical approaches, new equipment. Veterinary research very rarely addresses root questions about mechanisms, particularly in the area of behavior. Rather than asking “How are the brains of fearful dogs different?”, veterinary research is more likely to ask how we could fix a fearful dog: “Does this medication make a fearful dog less fearful?”

In fact, as I pursue my mechanism-based questions, I am asked if I miss being a veterinarian. The perception is that because I am engaged in basic, rather than clinical, research, I am no longer working as a veterinarian.

Basic science researchers

If veterinarians do clinical research studies, then who does basic research biomedical studies, studies that look not at how to fix problems but at how the body works? Ph.D. researchers are more likely to do this sort of research, which is why I am currently engaged in obtaining a Ph.D.

Traditionally, Ph.D. researchers have not been interested in dogs. In fact, way back in 2004 when I was originally deciding between a Ph.D. and a D.V.M., I was told by a Ph.D. animal behaviorist, “Ph.D.s don’t study domesticated animals. Veterinarians study those.” (Actually, veterinarians mostly just try to fix unhealthy domesticated animals, not study the healthy ones.)

That perception has changed in a big way in the intervening eleven years. There are now multiple laboratories studying dogs. But where does their funding come from — who cares enough about dogs as dogs, not as models for human problems, to provide the impressive funding needed for a genomics study? (The work I am doing for my Ph.D., sequencing messenger RNA, costs around $45,000.)

The U.S. federal government

The traditional source of funding for basic research is the federal government: the National Institutes of Health for health-based research and the National Science Foundation for more basic research. But these two massive institutions are very much focused on human health — as they should be, as they are funded by the tax dollars of American citizens. The economy can’t support all the research American researchers would like to do, and getting an NIH or NSF grant is becoming more and more difficult as grant funding is cut. Funding to study dogs as models of human disease? Maybe, but isn’t it easier to study laboratory rodents (on which you can perform invasive studies) or work on humans directly? Funding to study dogs as dogs? Go lie down until it passes.

In my experience, the small number of laboratories directly studying dogs are either studying them as models for questions about human health or evolution, operate on a shoestring budget, or have great trouble obtaining funding for what they want to do.

Animal welfare organizations

So who cares about dogs? Animal welfare organizations, some of which are national in scope and do perform research. Some major players in this field are the American Society for the Prevention of Cruelty to Animals (ASPCA), the Center for Shelter Dogs (CSD), and the Humane Society of the United States (HSUS). I am most familiar with the research coming out of the ASPCA and the CSD, and it is exciting stuff. But it is again mostly focused on applied questions: how can we help the shelter dogs in our care?

I reviewed some of the research these two organizations have performed on how to identify and treat food aggression in shelter dogs in my story for the Bark on shelter behavioral assessments. This was ground-breaking research and I am really glad to see it published. But it doesn’t ask the basic (i.e., non-applied) research questions I am interested in: what is it about the brains of these dogs that differs from the brains of dogs without food aggression? That kind of research doesn’t have immediate applied benefit. You can’t take it to a shelter worker with a recommendation about whether or not to put a food aggressive dog on the adoption floor. It is incredibly impressive that these shelter-focused organizations perform any research at all, and it is absolutely appropriate that the research they perform should have a highly applied focus, with clear questions that, when answered, will provide guidance on how to improve the lives of shelter dogs, immediately. They do not have the resources to pursue these sort of mechanism questions that I want to ask, which do not have immediate applicability.

So who cares about understanding how dog brains work, with the hope that that information will provide a base for future applied research? Who cares about the whole species, not just the subset in shelters or the subset in hospitals?

Breed organizations

Breed organizations care very much about the health and welfare of dogs, and in fact have provided funding into the mechanisms behind health issues specific to their breed. A recent paper about associations between spay/neuter status and health issues in Golden Retrievers was partially funded by the American Kennel Club’s Canine Health Foundation (AKC/CHF), and a similar study on Vizslas was funded by the Vizsla Club of America Welfare Foundation. (I blogged about these studies elsewhere.)

These organizations can fund basic research on how and why particular diseases occur in their breeds, and may even be willing to fund expensive genetic studies, such as a recent one on the genetics of cancer in Golden Retrievers, supported in part by both the AKC/CHF and the Golden Retriever Foundation. However, their focus is very much on the problems of a particular breed. My questions are broader: why do dogs of all breeds have different personalities, some more or less fearful? These organizations are really the caretakers of breed subsets of Dog, not of Dog itself.

Who, then?

Who does that leave as a group willing to fund studies on Dog? On problems common to all breeds? On problems which may or may not provide good models for humans? If I hope to one day run a laboratory which studies these problems, who can I hope to help pay for the research?

I would be remiss if I did not mention Morris Animal Foundation here. While their important Golden Retriever Lifetime Study happens to focus on the health issues of a single breed, their mission is to fund research into studies of small animals (dogs and cats), livestock, and wild animals, with no breed limitations. This group is doing important work, and I applaud them.

But one organization is not enough for a laboratory to depend on for survival, especially in these times with research funding so hard to come by. And so I wonder: are we, the dog lovers of the world, the ones to start supporting research into what it is to be a dog? We, who own dogs of all breeds and mixes, with all sorts of problems, who know what problems most plague us as owners — not just medical problems, but behavioral ones?

And so I leave you with my dreams of crowdfunding, in which a researcher proposes a study and asks the public to support it through donations. Such an approach allows the dog community to take the task of answering basic questions about Dogness into their own hands. This direct connection between a researcher and the community affected by their research is a new benefit of this age of social media. Is this approach right for this particular problem? Time will tell.

Image: Will crowdfunding work?

Monday, March 9, 2015

Contexts and cues: the reactive dog brain

A dog on leash, seeing another dog, explodes into a fury of barking and lunging. Reactive dogs, dogs who respond with arousal or aggression to what should be innocuous stimuli, can be very difficult for their owners to manage safely. I've written previously about hormonal changes in individuals experiencing this kind of arousal. But why do their brains trigger the stress response in such inappropriate situations in the first place?

Learning and memory

Past learning, stored as memories, has a lot to do with current behavior. If a dog has made bad associations with something in the past, he has a good chance of expecting a similarly unpleasant experience the next time he encounters it or something that reminds him of it. How he chooses to deal with this situation — aggression or withdrawal — is one interesting question, but right now I’m writing about how he makes associations in the first place and how he retrieves them later.

Learning and memory can mean a lot of different things depending on their context. I’ll be using them in a very narrow sense.

Learning: making an association between a stimulus and a consequence
Memory: the ability to retrieve a previously-formed association
So if a puppy is attacked by another dog, he may learn to associate other dogs with pain and fear. When he later encounters another dog, he uses his memory to retrieve that association. Two parts of the brain which are deeply associated with this type of learning and memory are the amygdala and the hippocampus.

The amygdala is associated with threat evaluation: is that twisty shape I see out of the corner of my eye a stick, or a poisonous snake? Is the dog I am greeting friendly, or about to attack me? People with damage to their amygdalas may have difficulty evaluating threats, to the extent that they may not be able to feel fear. As a result, the amygdala functions in emotional learning: people told scary stories remember them better than less exciting stories partly because of the emotional contributions of their amygdala, which tells them that an experience has some level of threat and should be recorded in memory with particular care.

The hippocampus, on the other hand, is famous for its contributions to learning different locations. London cab drivers must spend years memorizing the twisty street map of their city, and when they are done, their hippocampuses are actually larger in size compared to people who haven’t gone through the training.

When they work well, these two brain structures are an important part of the process of identifying appropriate threats and discarding stimuli that aren’t threatening, based on previous experience. So what exactly is going on when they operate as they should?

Fear conditioning: contexts and cues

The most effective studies that have been done to determine exactly how the hippocampus and amygdala function in learning and memory have used fear conditioning, often in laboratory rodents. Dog trainers use classical conditioning to associate stimuli that a dog considers threatening with something positive, to change the dog’s emotional response to that stimulus — for example, to teach a dog who fears other dogs that they will reliably get food when other dogs approach, so that the dog comes to look forward to the approach of another dog as a chance to get a treat. Fear conditioning researchers do the opposite, teaching a laboratory rat that something previously benign (like the sound of a bell) predicts something aversive (like an electric shock).

It’s unfortunate that so much research has been done on how to teach fear, something we don’t actually want to do in real life. However, what we learned from these studies should translate to the types of classical conditioning we do with dogs, and be even more relevant to helping us understand how fear-based behavior issues come about in the first place.

These studies have shown that that contexts and cues are important in classical conditioning. If you put a rat into a blue cage and then repeatedly play a bell right before shocking him, he will learn to fear the sound of the bell. The blue cage is the context; the bell is the cue. If you move the rat into a purple cage and play the tone without a subsequent shock, the rat will learn that the purple cage represents a different context, and that he does not need to fear the cue in that context. So the cue and the context contribute differently to classical conditioning.

Source:  Nature Reviews Neuroscience 14, 417–428 (2013)

In the case of a reactive dog, we might imagine that this dog spent time in a rough playgroup as a puppy, and learned to associate other dogs with being bullied. Here, the cue is another dog, and the context is the room the playgroup was in.

The hippocampus: learning in context

One of the jobs of the hippocampus is to encode contexts. Those London cab drivers with oversized hippocampuses have countless contexts encoded to represent many different locations around London. The hippocampus of the puppy who had a tough time at playgroup encoded the room where playgroup happened as a context.

In the case of our laboratory rats, the hippocampus encodes the blue cage as one context and the purple cage as another. With a healthy hippocampus, the rat can differentiate between the two contexts, and is fearful of the cue only in the appropriate context. But with a damaged hippocampus, the rat can’t differentiate between the blue and the purple cage. Although he was trained that the bell only predicts a shock in the blue cage, he fears both cages, because his hippocampus is unable to properly represent the context of the blue cage.

The associative amygdala

One of the jobs of the amygdala, on the other hand, is to encode associations. It encodes the association between cue and stimulus (bell predicts shock) and between context and stimulus (the shock only happens in the context of the blue cage). When humans were tested with functional MRI to see which regions of their brain became more active during a fear conditioning trial, the amygdala and hippocampus responded in different situations. When humans were trained to associate a cue with a shock, their amygdala activated in response to the cue. When they were trained to associate only a context with a shock, both their amygdala and their hippocampus activated when they were exposed to that context. The amygdala activated in both cases because the association was being recalled in both cases, but the hippocampus was only activated when the particular context was recalled. Fascinatingly, this study also found that humans with larger hippocampus volume had greater fear responses in fear conditioning trials. There was no association between amygdala size and fear response.

Prefrontal cortex as mediator

We are not, thankfully, completely at the mercy of the whims of our hippocampus and amygdala, subject to uncontrollable fears based on past bad experiences. We have some ability to take a step back and calm ourselves down. One of the parts of the brain involved in this higher-order cognition is the prefrontal cortex (PFC). This region of the brain has direct connections to both the hippocampus and the amygdala and appears able to mediate some of the signals coming from those two regions. Functional MRI studies tell us that while fear acquisition involves the amygdala, fear extinction (learning to let go of a fear) involves the PFC as well. We also know that people who have thicker PFCs are better at extinguishing fear associations. This mediation by the PFC is what lets us take a deep breath and choose not to give in to our fears.

Do dogs have this ability to take a step back and try consciously to decrease their fears? Certainly they are not as good at this skill as humans are, but I wonder if they do have some ability to do this. In a recent post at Reactive Champion, a reactive dog owner describes a situation in which she believes her reactive dog did just that.

PTSD: failure to contextualize?

When this system goes wrong, how does it go wrong? One hypothesis suggests that post-traumatic stress disorder (PTSD) is a disease of failure to contextualize. Humans with PTSD report having flashbacks to previous trauma unexpectedly and uncontrollably, and in inappropriate contexts. If you were in a drugstore during a robbery, it would be appropriate for you to remember that traumatic event when you returned to that location, and even to feel trepidation about entering that store again. You’d probably think about the event a lot for the first days, weeks, perhaps months afterwards, in many other contexts, as well. But your brain should recover, and you should eventually come to not think of it constantly, and only be reminded of it in similar contexts, such as the same or similar locations.

People with PTSD, however, may have trouble limiting their recall of traumatic events to similar contexts, so that they may be retrieving these memories (often vividly) in any and all contexts, years after the trauma has passed. The problem may lie with their hippocampus, which may have difficulty limiting recall by context. And indeed, studies have shown that people with PTSD often have smaller sized hippocampuses compared to the healthy population.

The perspective of the reactive dog

On to the realm of pure speculation, then, because studies haven’t been done in hippocampus function in reactive dogs. But I think the story of the person involved in a trauma who can’t appropriately contextualize her memories is similar to the story of the dog who was involved in a trauma (dog attack, overwhelming experience in a crowded area as a puppy) and can’t contextualize the experience. A dog who is attacked by other dogs at a dog park may learn to fear the dog park, but if never attacked outside of the dog park, should he learn to fear all dogs, everywhere? I’d argue that that’s an inappropriate association for his brain to make, and that the mechanism of failure might have to do with a failure of the hippocampus to appropriately contextualize, just as in someone with PTSD.

I’m certainly not saying that all reactive dogs have PTSD, but I am speculating that the mechanisms might be similar. Does hippocampal function vary across a spectrum, with some individuals having high-functioning hippocampuses and others not so effective ones? Do dogs with hippocampuses on one end of that spectrum have difficulty limiting their negative associations, such that they are more likely to suffer from fearfulness and possibly fear aggression? I don’t know, and I don’t know if the research will ever be done, but it’s an intriguing story to consider.


  • Maren, Stephen, K. Luan Phan, and Israel Liberzon. "The contextual brain: implications for fear conditioning, extinction and psychopathology." Nature Reviews Neuroscience 14.6 (2013): 417-428. [PDF]
  • Feder, Adriana, Eric J. Nestler, and Dennis S. Charney. "Psychobiology and molecular genetics of resilience." Nature Reviews Neuroscience 10.6 (2009): 446-457. [HTML]

Tuesday, March 3, 2015

Brain regions and their functions

[Note: this infographic is intended for use in my online class, The Canine Brain: From Neurons to Behavior, which starts tomorrow (March 3, 2015). Check it out if dog brains interest you, and/or if you're a dog trainer looking for CEUs!]

Friday, February 27, 2015

Do spayed and neutered dogs get cancer more often?

[Note: this post was originally published at the lovely Julie Hecht's Dog Spies blog at Scientific American.]

Where I live, in America, it’s taken for granted that responsible owners spay or neuter their dogs. The population of homeless animals is still large enough that risking an unwanted litter is, to many owners, unthinkable. And spay/neuter is just what people do. But two papers were published, in 2013 and 2014, suggesting that these widely accepted surgical procedures may lead to increased long-term risk of certain kinds of cancers. These studies ignited a debate which had been smouldering for years: are there unwanted health consequences associated with altering a dog’s levels of estrogen or testosterone?

The 2013 paper looked at Golden Retrievers. The authors reviewed data from veterinary hospitals, comparing Goldens who were diagnosed with various diseases, those who were not, and the spay/neuter status of each group; they found a correlation between spaying or neutering and cancers such as osteosarcoma, hemangiosarcoma, and mast cell cancer. The 2014 paper used a voluntary Internet-based survey to perform a similar investigation in the Vizsla breed. They also found correlations between spay/neuter status and mast cell cancer, hemangiosarcoma, and lymphoma.

These are scary results, but I caution that studying the causes of multi-factorial diseases like cancer is incredibly challenging. Take the Golden Retriever study, a retrospective study using data from a veterinary referral hospital. This study was limited to dogs whose owners chose to bring them to a relatively expensive referral hospital. This is the kind of place where you take your pet when he has cancer and you are willing to spend a fair amount of money to help him. As a result, this hospital’s records probably provide a great source of data on companion animals living with concerned owners, particularly owners who have provided excellent medical care for much or all of the animal’s life. However, this hospital’s records are less likely to provide data on animals whose owners have provided sub-optimal care. This kind of bias in sample selection can have a significant effect on the findings drawn from the data.

The Vizsla study used an Internet-based survey instead of hospital records. Like the Golden Retriever study, this study could have found itself with a biased sample of very committed dog owners, in this case owners who engaged in dog-focused communities online and who had enough concern about the health of the breed to fill out a survey. This study additionally suffered from a lack of verified data; owners were asked to give medical details about their dogs and may have misremembered or misinterpreted a past diagnosis.

Don’t get me wrong – these were both important studies, and they did their best with the available resources. I applaud both sets of authors for putting this information out there. But the studies both have their limitations, which makes their findings difficult to trust or generalize to other populations of dogs.

Meanwhile, another 2013 study presented some other interesting results. This study drew data from multiple referral hospitals to determine the causes of death in spayed or neutered versus intact dogs – and they found that spayed and neutered dogs, on average, lived longer than intact dogs. Intact dogs were more likely to die of infectious disease or trauma, while spayed or neutered dogs were more likely to die of immune-mediated diseases or (again) cancer. In other words, while spayed or neutered dogs did get cancer, it didn’t seem to shorten their lifespans.

This study shed a new light on the cancer question. It suggested that perhaps spayed or neutered animals might be more likely to get cancer simply because they were living long enough to get it. Intact animals were more likely to die younger, perhaps simply not aging into the time of life when the risk of cancer rises.

So where does that leave us? Is there a causal link between spaying/neutering and cancer? I think the question is still wide open. What we really need is a study that follows animals forward throughout their lifetimes instead of using retrospective records or surveys to get the data – and, thanks to Morris Animal Foundation’s groundbreaking Golden Retriever Lifetime Study, we are getting just that. This study is enrolling Goldens as puppies and following their health over the course of their lives. It will be years before the study gives us answers, but it provides hope for more solid data. (Of course, it still can’t address the issue of bias, in that owners who enroll their puppies in this study could be highly responsible dog owners who provide excellent medical care!)

We can, however, do something about cancer in dogs without waiting for the results of that study. It is no coincidence that two of the studies discussed here investigated Golden Retrievers. Sixty percent of Golden Retrievers will die of cancer. That is indisputably a problem with the genetics of the breed, and other breeds suffer from similar problems. We should be attacking cancer on all fronts, and this is a front we don’t have to study first. Golden Retriever breeders are between a rock and a hard place, trying to breed for health in a gene pool which doesn’t have enough genetic diversity to support it. The solution is to bring in new blood from gene pools with much lower risk of cancer, breeding dogs who don’t look like purebred Goldens for a few generations to revitalize the breed as a whole. Genetics contribute far more to risk of cancer than whether an animal is spayed or neutered. We clearly have a strong desire as a society to reduce the incidence of cancer in Golden Retrievers and other breeds. While we’re studying risk from spaying and neutering, let’s address the genetics question that we know we can fix.

Image: Rob Kleine, Golden Retriever, Flickr Creative Commons License.


Torres de la Riva G, Hart BL, Farver TB, et al. Neutering Dogs: Effects on Joint Disorders and Cancers in Golden Retrievers. PLoS ONE 2013.

Zink MC, Farhoody P, Elser SE, et al. Evaluation of the risk and age of onset of cancer and behavioral disorders in gonadectomized Vizslas. Journal of the American Veterinary Medical Association 2014;244:309–319. [Paywalled]

Hoffman JM, Creevy KE, Promislow DEL. Reproductive Capability Is Associated with Lifespan and Cause of Death in Companion Dogs. PLoS ONE 2013.

Monday, February 2, 2015

The rough guide to the fight-or-flight response

[Note: This post is intended as reading material for my upcoming online course, “Canine Hormones: From molecules to behavior.” This is an entirely online course offered through APDT, begins Februrary 11, and is worth 12 CEUs. I posted with more information. I encourage you to sign up!]

First, some terminology. I've been posting about the stress response recently. What's the difference between the fight-or-flight response and the stress response? It depends on who's talking. I like to use the term “stress response” to refer only to the hypothalamic-pituitary-adrenal (HPA) axis, best known for managing the levels of cortisol in the bloodstream. I use the term “fight-or-flight response” to refer to the sympathetic-adrenomedullary (SAM) axis, best known for managing the levels of adrenaline in the bloodstream. However, some people also refer to the SAM as the “stress response,” and some subdivide the two into the “slow arm of the stress response” (the HPA) and the “fast arm of the stress response” (the SAM).

The SAM is certainly fast! This is because it sends information straight from the brain to the adrenals through the nervous system instead of having to pass the message through a couple of other hormones first.

The sympathetic nervous system

By OpenStax College
[CC BY 3.0 (]
via Wikimedia Commons

What it is: a subset of the involuntary nervous system, also known as the autonomic nervous system. The autonomic nervous system is subdivided into the sympathetic nervous system, which handles the fight-or-flight response, and the parasympathetic nervous system, which handles the rest-and-digest response.

What it does in the SAM: passes an electrical signal from the brain along the spinal cord and out to the adrenal glands.

The adrenals

via Wikimedia Commons

What they are: small organs next to the kidneys responsible for sending all kinds of important hormones out into the body

What they do in the SAM: in response to input from nerves of the sympathetic nervous system, they release adrenaline (also known as epinephrine) and noradrenaline (also known as norepinephrine) into the bloodstream so that they can alert different organs and tissues around the body to the need to respond to a stressor fast, fast, fast. Note that the adrenals also release a hormone in the HPA axis. The adrenals are complicated little organs with different regions involved in the production and release of different hormones. In the case of the SAM, the interior region of the adrenals, the medulla, is the responsible party. The medulla contributes the M to SAM. (The outer layer of the adrenals, the adrenal cortex, is the active region in the HPA axis.)

The minor players

The rest of the body

When adrenaline shoots into your bloodstream — well, you know what that feels like. Some people like the sensation; they are the types who seek out rollercoasters and horror movies. Some people hate it. Adrenaline tells your body to mobilize all its resources for a short term threat: your muscles get extra energy, the pupils of your eyes dilate to take in more light so you can see better, your heart beats faster and stronger, your lungs take in more air. It doesn't last long, just a minute or so.

Although this response is classically associated with fight (going on the offensive) or flight (getting away from a bad situation), another common behavior associated with this response is freezing: holding very still. This is a common response in some kinds of prey animals, like mice, but any species might react this way.

The brain

What causes the fight-or-flight response to start? Different stimuli are scary to different individuals. I'm terrified of spiders and my cousin is terrified of snakes. On one particular walk in the woods she and I encountered one of each and took turns being scared and laughing at each other.

The HPA axis

The HPA and SAM axes are intricately connected. If your SAM axis is triggered frequently, your HPA axis will start pumping out more cortisol — and if your HPA axis is chronically active, your SAM responses may become more intense. During the long chronic stress of veterinary school, one of my friends reported that she dropped a glass by mistake, and when it shattered, she screamed. The long-term high levels of cortisol in her bloodstream from the stress of veterinary school were affecting her adrenal medulla, making her adrenals pump out more adrenaline in response to acute stressors like the noise of breaking glass.

Sunday, January 25, 2015

The rough guide to the stress response

[Note: This post is intended as reading material for my upcoming online course, "Canine Hormones: From molecules to behavior." This is an entirely online course offered through APDT, begins Februrary 11, and is worth 12 CEUs. I posted with more information. I encourage you to sign up!] 

The series of organs working together to form to stress response are called the hypothalamic-pituitary-adrenal (HPA) axis. This post is a reference to them. The major players are:

The hypothalamus

The hypothalamus
Licensed under CC BY-SA 2.1 jp
via Wikimedia Commons
What it is: part of the brain, an important link between the nervous system and the endocrine (hormonal) system

What it does in the HPA: in response to input from other parts of the brain, releases cortocotropin-releasing hormone (CRH) into blood vessels which take it directly to the pituitary and not into the rest of the body

The pituitary
Emplacement de l'Hypophyse
Patrick J. Lynch, medical illustrator
via Wikimedia

The pituitary

What it is: a little gland hanging off the bottom of the brain. Some people consider it part of the brain and some don't.

What it does in the HPA: in response to hormones coming through the blood directly from the hypothalamus (not going out through the rest of the body first), sends adrenocorticotropic hormone (ACTH) out to the rest of the body

The adrenals

What they are: small organs next to the kidneys responsible for sending all kinds of important hormones out into the body

What they do in the HPA: in response to ACTH in the bloodstream, release cortisol into the bloodstream so that it can alert different organs and tissues around the body to the need to respond to a stressor

The minor players

Those are the three organs which are part of the name of the stress response: the hypothalamic-pituitary-adrenal (HPA) axis. But to some extent, humans just chose those three as the central parts of the axis because we understood their functions first. Other organs are important in the functioning of the stress system too.

The hippocampus

What it is: a part of the brain associated with learning and memory

What it does in the HPA: assesses the amount of cortisol in the bloodstream and sends a negative feedback message to the hypothalamus to tell it to slow down the HPA axis (resulting, eventually, in the release of less cortisol from the adrenals). This is probably part of how socialization works: the hippocampus undergoes epigenetic changes early in life which make it more or less able to send the “slow down” message to the hypothalamus and put the brakes on the stress response.

The amygdala

What it is: a part of the brain associated with fear

What it does in the HPA: the amygdala is part of the system that sends that initial message of fear when an animal encounters something scary, triggering the initial HPA axis stress response.

The liver

What it is: an organ that makes a lot of useful substances used for various things in the body

What it does in the HPA: makes corticosteroid-binding globulin (CBG), the little protein that carries cortisol around in the blood stream. CBG does more than just ferry cortisol about; it actively spits it out in locations where it's needed, and when an animal has very low levels of CBG, the entire HPA axis becomes less reactive. Very young animals have low levels of CBG, which may contribute to their early lack of fear.