Lindsey Kitchenham (00:04):
I always wanted to be an animal researcher and I've always been interested in animal behavior, but neuroscience is coming up as this new, exciting field that everybody's getting into, and it just helps you unlock the questions that you have remaining about behavior.

Graeme Li (00:24):
You're listening to the Why & How Podcast, produced by the Ontario Agricultural College of the University of Guelph, where we look to answer big questions in agriculture, food, and the environment through casual conversations rooted in research.

Graeme Li (00:41):
Hello. Hello. And we're back in the studio. Unfortunately, Jordan isn't with us today, but he will be joining us on the next episode, don't you worry. I miss him too. But we're here with Lindsey Kitchenham. Lindsey, hi.

Lindsey Kitchenham (00:54):
Hey, how's it going?

Graeme Li (00:55):
Good, good. And we're here to talk about your research, but first, why don't you tell me a little bit about yourself.

Lindsey Kitchenham (01:01):
All right. My name is Lindsey Kitchenham. I am a second year masters by thesis student in the Ontario Agriculture College, obviously, in the Department of Animal Biosciences. I'm doing a neuroscience collaboration, so that means I've got both animal biosciences and neuroscience on my degree. I did my undergrad here at Guelph in actually Psychology: Brain & Cognition. So this program's been canceled now and has been replaced with the neuroscience program, which I did as a minor. So my background is heavily in neuroscience, but I've always had a passion for animals, which drew me to the animal biosciences, and thanks to the neuro collab, I get to do both, which is what my research is about.

Graeme Li (01:49):
And so what is your research exactly? Could you give us a brief little synopsis about that?

Lindsey Kitchenham (01:54):
Yeah, so I get to work with laboratory mice, and basically, I get to ask questions about why do they express abnormal behaviors when they're kept in cages that are very tiny and very empty. So I'm actually looking at their brains to see why they do some of these weird behaviors.

Graeme Li (02:13):
So what are these behaviors that we're talking about?

Lindsey Kitchenham (02:16):
All right. Well, these are called stereotypic behaviors. And some examples for what the laboratory mice do is they do these backflips. They just constantly backflip all day long. Or some of them might spin around in really tight circles, like a dog chasing its tail. Others gnaw on the bars of their cage, or run around in circles. And these just happen all day long. So those are the laboratory mice stereotypic behaviors. But these are also common in zoo and farm animals. So if you've been to the zoo, you've probably seen tigers pacing around their enclosure, or polar bears swaying back and forth. It's, again, caused from a poor fit in housing. Farm animals do these things too. Pigs biting on chains, chickens feather-plucking. It's a very common occurrence due to poor housing conditions.

Graeme Li (03:09):
And so for all these animals, is this when they're solo only?

Lindsey Kitchenham (03:13):
No, they even happen in social groups. So laboratory mice are social animals and they're often group housed. Pigs, for example, you can have multiple pigs in a pen, but they'll still express things like tail biting. So it can happen when they're alone and isolated, which might be the case for a polar bear. There's only one or two in the zoos. But it does happen when animals are housed in groups as well.

Graeme Li (03:36):
So for the mice, what are the cages like for a standard laboratory?

Lindsey Kitchenham (03:41):
Yeah. So a standard laboratory housing cage is about the size of a small shoe box. So not much bigger than a Kleenex box. They have a substrate of bedding. So basically, if you think of just picking up a bunch of pebbles or sand off the ground, spread that on the floor of the cage, and that's usually it. Sometimes they're provided with nesting material, which is often crinkle paper or a little bit of cotton wool. But especially in medical studies, and in immunocompromised mice, they are not given anything in their house.

Graeme Li (04:18):
And is the box made out of glass, or cardboard, or what type of material?

Lindsey Kitchenham (04:23):
It's a very durable plastic. So it's transparent for the researcher to see through. But that's not great for the mice because they're a prey species. So that's actually even more adversive to them to have these scary giant humans watching them all the time. So that just adds to their stress. Sometimes they're given houses, but again, if you're a medical experiment mouse, you're often not given anything at all. So you're cold and you're exposed.

Graeme Li (04:53):
So why do we use mice in research?

Lindsey Kitchenham (04:56):
Well, first off, because they're small, they're very easy to house, so they're inexpensive. Second, they have a really quick generation span, so you can breed tons and tons and tons of them. Third, and this is the biggest reason, mice can be genetically modified and rats can't. So a lot of research, for example, Alzheimer's research, which is a huge thing here on campus, uses genetically-modified mice to express the tau protein so that researchers can study the pathology.

Graeme Li (05:27):
So for these mice, how will these conditions affect their research, potentially?

Lindsey Kitchenham (05:33):
Well, it could have negative effects on the research, but we don't really know as scientists right now. This is just a hypothesis that is going around. So you could think, for psychological research, for example, or neuroscience, if you have an animal that does not have a normal brain due to its housing conditions, so these tiny, empty, barren houses, they negatively affect the brain development. And now you want to make conclusions about normal humans based on this abnormal animal? Well, that might not make sense. It might not work.

Lindsey Kitchenham (06:10):
Drug studies, especially psychological drug studies. When you're trying to develop something for, say, depression and you're testing it on these mice who you've induced depression in them, but they also might have poor brain development. You test your drug out, it might work on those individuals, but it might not work on regular depressed humans who grew up in a normal environment. So there might be a bit of a translation gap, although this has not been thoroughly tested in research yet. It's just a new idea that's kind of been passed around and people are getting very excited to start testing this question out.

Graeme Li (06:49):
I remember when we were talking before, you gave me an example of a psychological experiment. Could you talk about that one? I forget what the name of the person was.

Lindsey Kitchenham (06:57):
The case of Genie?

Graeme Li (06:58):
Yes.

Lindsey Kitchenham (06:59):
Yes. Okay. So Genie is a famous psychological case. So if you're a psychology student, you might've heard about different case studies. So Genie is one of the case studies that come up when we're trying to understand the difference between nature and nurture. So a long time ago, scientists were curious to see what makes a human a human. So for instance, we have speech and many other animals are not capable of language. This is considered an innately human quality. Are we all born with this quality, or do we have to develop it and learn about it?

Lindsey Kitchenham (07:37):
Well, Genie, unfortunately, was severely abused as a child. Her family kept her in a room all by herself. Very sad case. But psychologists could then use that experience of basically complete deprivation and no input from outside environment to study what happens. Well, Genie was not capable of speech. She was severely mentally delayed despite not having any kind of genetic reason to be. And so she came out of that situation and was severely disabled. So it's like if you raise a mouse in an empty cage with nothing inputting on the brain's development, you could come out with the same severely disabled brain.

Graeme Li (08:29):
And obviously you would not want that as a model for your drug to try and prove for a normal human.

Lindsey Kitchenham (08:35):
Exactly. It might be effective on people who had severe trauma in their childhood growing up, who later develop depression. But most of us, thank goodness, that is not the case for all of us.

Graeme Li (08:49):
So what does a typical day look like in your lab right now?

Lindsey Kitchenham (08:52):
So right now, I'm actually working on brains that have been collected from an old cohort of mice. So the two masters students before me, they observed the behaviors of these mice housed in either standard laboratory cages, or large complex cages that have what we call enrichments that allow them to engage in natural behaviors. So when they look at these two different types of cages, they compared their behaviors. So the standard housed mice are very stereotypic, and the enriched housed mice are not stereotypic. So I have all of their brains and I have all of the data for their entire lifetime. So mice live for about two years, so I have two years' worth of behavioral data. It's quite a lot.

Lindsey Kitchenham (09:40):
So now that I have their brains, I have to take a look inside. And what I'm looking at is actually brain activity. So long-term brain activity that allows me to estimate sort of what are the basal levels of what the brain was doing across their entire lifespan. So to do that, I have to first cut the brains up into tiny little sections in order for them to take a chemical stain. So the chemical stain that I'm using is actually a metabolic marker. So metabolic activity is highly correlated to neuron activity. This allows me to estimate what brain regions were more or less active in certain mice. So I'm just kind of getting into that now. And that involves working with a lot of new chemicals that I never got to work with as a psychology student.

Graeme Li (10:32):
And metabolic activity, is that like digestion, or?

Lindsey Kitchenham (10:36):
In the brain, it's the exchange of oxygen to produce ATP. So when a neuron fires, it needs ATP in order to stabilize its membrane potential. So basically, a neuron fires, it sends an action potential, so an electric current. That changes the charge of the membrane. So in order to come back to normal and then fire again, the neuron needs ATP. So the metabolic marker that I'm looking at helps make ATP. So as the neuron fires more, this metabolic marker gets more and more expressed and more and more active. So in the neurons that are firing a lot, I should have a lot of deep stain for that marker. And in the neurons that are firing a lot less, I should have much less stain of that marker.

Graeme Li (11:29):
Okay. So increased ATP activity means increased brain activity, more or less.

Lindsey Kitchenham (11:35):
Yeah. Yep.

Graeme Li (11:35):
Okay. And so with the data from the other project, how are you going to combine that with your data to look at something, look at changes?

Lindsey Kitchenham (11:44):
Yeah, so I'm going to basically create a statistical model. So it's supposed to mimic the way that the brain and the behavior might interact. So basically what I'm looking at is how 16 brain regions can explain the type of behavior that the mouse is expressing.

Graeme Li (12:05):
And so you use a model with those 16 and try and correlate them with behaviors?

Lindsey Kitchenham (12:10):
Yeah, it's basically like plotting points on a graph, and seeing how well they connect together.

Graeme Li (12:17):
Okay. Interesting. And so how did you get into this research?

Lindsey Kitchenham (12:21):
Yeah, well, it started in my undergrad. I did a collaborative project in psychology for basically my honors thesis, and that's where I met my advisor, Dr. Georgia Mason. She was always very interested in animal behavior, which was what I was interested in. And she had a postdoc student at the time who was looking at the same sort of questions I'm looking at, but in farmed mink. So I actually got to look at mink brains and sort of collect some data for them, and that's how I got introduced to the project. And I'm basically carrying on the legacy of her postdoc student.

Graeme Li (13:02):
And so do you ever consider these mice as pets almost? Do you bond with them?

Lindsey Kitchenham (13:08):
Yeah, I say I would have bonded with these mice, especially because I spend a lot of time with them, observing their behaviors. I've gotten to know them and they definitely have their own kinds of personalities. So one interesting thing is that we work with three different types of mice. So a brown mouse, a white mouse, and a black mouse, and they all behave very differently. So the brown mice, they're the ones that show all this stereotypic behavior. So backflipping all day long, running around in circles. And the white mice are very calm, and same with the black mice. So you'll see some funny scenes where a white mouse might just be minding her own business and chewing on food in the cage. And the two brown mice are running circles all around her and she's just in caught in the middle of the whirlwind. So they do grow on you, you do get attached to them. It is quite sad when you have to kill them to collect their brains.

Graeme Li (14:10):
And so for the cages, how do you think they could be improved to maybe make the mice have a happier life, I guess?

Lindsey Kitchenham (14:18):
Yeah, so that's a little bit difficult when you're considering one, tech time in the laboratory. You have to pay people to take care of these cages. And two, how many cages you can fit into a lab room. So that's one of the main reasons that they're so small and very easy to handle. So what we could do is just change the height of the cage a little bit and put in a second level. That gives them a little bit more of something to do. What I'm concerned about is that this won't be enough for the welfare of the mice. In reality, they might need huge, complex cages that laboratories never would effectively be able to supply and take care of.

Graeme Li (15:05):
So what would be the implications of your research once it comes out, and what would you hope that would potentially change in the cage mice researched industry?

Lindsey Kitchenham (15:14):
So the CCAC, which is the Canadian Council of Animal Care, they're basically the ethical council that oversees all animal research. So before you do anything with an animal in the lab, you have to get ethical approval by the CCAC. Well, they have a set of guidelines that you have to classify your type of research into, called the invasiveness guidelines. So these rank from A to E, and E is the highest level of invasiveness. So at this level, these are things that you're doing to mice that you wouldn't do to humans ever. So things like causing concussion, causing tumors. One level below E is D, and this states that at this level, anything that you do might cause permanent sensory motor dysfunction. So sensory motor, that relates to the brain. So anything that you cause the brain to no longer act normally would be the second highest level of invasiveness. So if I find out that standard laboratory housing causes brain dysfunction, should standard laboratory housing be reclassified as a level D, the second highest level of invasiveness? I don't know.

Graeme Li (16:37):
Potentially, right?

Lindsey Kitchenham (16:38):
Yeah.

Graeme Li (16:38):
Potentially. And so what would be the implications if that classification went forward?

Lindsey Kitchenham (16:43):
Well, then the standard of housing would change. Everyone would have to provide much better housing for their mice, because it would no longer be ethical to just keep them in cages that causes brain dysfunction when you don't need to be doing that. So if you just want to do simple experiments, like simple social experiments, simple memory experiments, your mice would have to be housed in environments that are much better for their welfare.

Graeme Li (17:09):
And so, Lindsey, why do you care about these animals?

Lindsey Kitchenham (17:12):
Well, I have a bit of bias because I have pet rats, so I already very much love rodents, but rodents are often overlooked. They're the most used research animal all over the world. So going right off of that, that's because people don't care very much about them. But they're living beings. They feel pain, they feel emotions. We need to treat them with the same amount of consideration that you would treat your pet dog, your cat, your best friend.

Graeme Li (17:46):
And so during your research, why do you think brown, black and white mice act differently?

Lindsey Kitchenham (17:51):
Because they have different genetic backgrounds. So the white mice are called BALB/Cs. The black mice are called C57s, and the brown mice are called DBAs. And basically, researchers breed mice for different purposes in research. So these three types of mice are the most commonly ones used. So they're the ones that we use.

Graeme Li (18:12):
Okay. And just based on those genes, do you think that probably affects their behaviors?

Lindsey Kitchenham (18:18):
I think it first affects their personalities and then it affects their behaviors. So some mice are more laid back, some mice are more adventurous, some mice are very nervous, and some mice are very, very bold. Like the white mice, they are extremely bold and very nice to people, but apparently they're not nice to other mice.

Graeme Li (18:39):
Oh, interesting. So yeah, they really do develop a personality, then.

Lindsey Kitchenham (18:42):
They definitely do.

Graeme Li (18:44):
Okay. Your pet rats, what are they like? Are they similar to mice, would you say?

Lindsey Kitchenham (18:48):
Rats are very different than mice. So I would describe rats as pocket dogs, and mice would be pocket cats.

Graeme Li (18:58):
Could you go a little deeper into that? That is a loaded statement that I've never heard before in my life.

Lindsey Kitchenham (19:03):
Yeah. So rats are very social. They're very forgiving of humans, and they're very tolerant of how you handle them, and how you treat them. So you could pick a rat up and just mush around with it and kiss it and do whatever you'd want to do, that you would do to a dog. And then you put them back down, and they still run right back up to you. They greet you when you come home. They really love human attention. Whereas mice, they're better off on their own. They don't mind if you don't come around a lot. They do appreciate when you come and give them treats, but they don't need to spend that much time with you. And if you make them angry, they likely won't forgive you for a little bit.

Graeme Li (19:43):
Wow. Okay. Well, I want to dig into this more actually. Do you let your rats around the house freely?

Lindsey Kitchenham (19:50):
Yeah, so sometimes. So right now, they're in a cage, a very large cage. It's about the same height as me. And when I get home, or in the morning, I let them run around my room free. I used to have two male rats who lived in the living room, and I would just open the door to the cage and let them go all around the house. And they would go all around the house. They would go upstairs into my room, sleep on my bed. They had a little clubhouse in the living room that they would go to, or they would go and sleep in their cage. So they could make decisions about where they wanted to be at whatever time.

Graeme Li (20:27):
Can you potty train a rat?

Lindsey Kitchenham (20:28):
Yes, you can.

Graeme Li (20:28):
Wow. That is really impressive.

Lindsey Kitchenham (20:29):
Yeah.

Graeme Li (20:32):
Oh my goodness, that is really like a dog. You would never think that.

Lindsey Kitchenham (20:34):
Yeah. Yeah. I've never been successful at doing it, but I adopted a couple of rats from a foster family who had potty trained them and it was very convenient.

Graeme Li (20:47):
So with the psychology background, did you ever think you'd be like in the lab really cutting up brains actually?

Lindsey Kitchenham (20:52):
Actually, I never expected to be doing this. So I was always interested in behavior, and I thought I hated neuroscience, and maybe I hated it because it was so hard. And it is. It's still very, very hard. But I love what I do because I love the purpose that it carries with what I do. I always wanted to be an animal researcher and I've always been interested in animal behavior, but neuroscience is coming up as this new, exciting field that everybody's getting into, and it just helps you unlock the questions that you have remaining about behavior.

Graeme Li (21:29):
And so what other questions would you like to ask while continuing as a researcher, if you think you're going to do that?

Lindsey Kitchenham (21:36):
Well, my passion has always been communication and empathy. So looking at animal empathy. Did you know that rats had empathy?

Graeme Li (21:46):
I did not.

Lindsey Kitchenham (21:47):
Yeah. So if you trap a rat in a cage and you allow another rat to sort of learn how to open the cage, they will always open the cage of the trapped rat, even if there's treats and other fun things around. They'll save a drowning family member, and they'll avoid causing harm to another rat, even if they would get a treat for hurting them. So rats have incredible empathy, and I've always been very interested in this, as well as how they communicate what's actually happening to them at that time.

Graeme Li (22:22):
So do you think rats get a really bad rap in our culture?

Lindsey Kitchenham (22:25):
Definitely. Rats are one of the sweetest animals. The worst thing that you could think of is that dirty rat. Rats are clean, rats are lovable, and rats are friendly.

Graeme Li (22:37):
Okay, okay. Even wild rats?

Lindsey Kitchenham (22:41):
Even wild rats.

Graeme Li (22:42):
Okay, well, people will have to take that home and think about it, I think, a little bit.

Lindsey Kitchenham (22:48):
Yeah.

Graeme Li (22:48):
That's going to take a lot of empathy on our part, probably, to come around to that conclusion. But maybe one day people will catch and release them, hopefully.

Lindsey Kitchenham (22:56):
If you ever get a chance to interact with a rat, I highly recommend it. They're very lovable creatures, once you get to know them.

Graeme Li (23:02):
Maybe do it with a pet rat instead of one you find on the street, to start that, right?

Lindsey Kitchenham (23:05):
That's a good idea.

Graeme Li (23:08):
Moving on, where do you see yourself in two or three years, once the project wraps up?

Lindsey Kitchenham (23:13):
Yeah, so I'm hoping to go onto my PhD, and basically continuing on with this research and building on it. So the first step is finding out if there's brain dysfunction in standard housed stereotypic mice. The next step for me would be seeing if this brain dysfunction causes other impairments to the mice that could be harmful to them. So are they less able to forage properly? Are they less helped in social situations, or do other mice dislike them? Does it affect their mothering qualities? Questions like that. And then combine my findings with those behavioral measures and the neuroscience measures to sort of ask, is this a disorder in mice?

Graeme Li (24:00):
So the mouse behaviors are actually really complex. I didn't know they had all these different. Do they form social hierarchies and stuff like that?

Lindsey Kitchenham (24:07):
Yeah. They form social hierarchies. Most pups are highly dependent on their mothers, so they have very complex maternal behaviors. They have complex social systems. So their behavior is very important for mouse survival.

Graeme Li (24:24):
Interesting. And do you plan on continuing your work in the same lab with Dr...

Lindsey Kitchenham (24:31):
Georgia Mason.

Graeme Li (24:31):
Georgia Mason. Yes.

Lindsey Kitchenham (24:33):
Yeah, definitely.

Graeme Li (24:34):
Shout out, Dr. Georgia Mason.

Lindsey Kitchenham (24:35):
Georgia. Yes, definitely. That is the plan.

Graeme Li (24:39):
Just wrapping up here, are there any other comments you'd like to say about animals and maybe their consciousness?

Lindsey Kitchenham (24:46):
Yeah, don't judge a book by its cover. Get to know them first.

Graeme Li (24:50):
All right. Lindsey, thank you very much for being here. Are there any shout-outs you'd like to give, other than Georgia Mason, of course?

Lindsey Kitchenham (24:57):
And the Mason lab, and [inaudible 00:24:59] lab, and my rats at home, Cinnamon and Cocoa.

Graeme Li (25:04):
All right. Thank you very much for being here. And that's a wrap. The Why & How Podcast is published by the Ontario Agricultural College of the University of Guelph. It is produced by Stephanie Craig and Jordan Terpstra. Recording and editing by Jakub Hyzyk and Kyle Ritchie. The host is me, Graeme Li. If you liked what you heard, be sure to leave us a review and subscribe. Thanks for listening.