The future of parent-child bonding

0:00This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. I thought it would be good to revisit the original intent of this show. In 2017, when we started, we wanted to create a forum to dive into and discuss the motivations and the research that my colleagues do across the campus in science, technology, engineering, medicine, and other topics. Stanford University and all universities, for the most part, have a long history of doing important work that impacts the world. And it's a joy to share with you how this work is motivated by humans who are working hard to create a better future for everybody.

0:37In that spirit, I hope you will walk away from every episode with a deeper understanding of the work that's in progress here, and that you'll share it with your friends, family, neighbors, co-workers as well. Their mom like comes in and then the tadpole is like, oh, that's my mom and they recognize her based on smell so they can smell their mom versus and tell her apart from not mom and then they're like oh this is my mom i need to tell them i'm hungry and so they do this little dance behavior and so we've been able to work out like oh the you know the tadpoles are recognizing them by smell then this activates these neurons which then activates this circuit and then this is how like if we turn on this neuron then this is how this tadpole communicates that it needs food because we don't understand a lot about how, you know, communication and kind of parental recognition happens in the infant brain.

1:31And so we've been able to work that out in tadpoles. And, you know, now people have a blueprint of what to look for in other organisms like mammals.

1:45This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. If you're enjoying the show or if it's helped you in any way, please consider sharing it with friends, family, colleagues, neighbors. Personal recommendations are a great way to spread news of the future of everything. Today, Lauren O 'Connell will tell us that a great way to understand parenting and parent-child interactions is by studying poison frogs. It's the future of parenting chemistry. Before we get started, a reminder that if you're enjoying the show, please spread the word to friends, family, neighbors, and colleagues, anybody who you like, to tell them about the future of everything and how you're finding it interesting.

2:34So all species have to manage parent-child relationships. Many of us are well aware that it is not easy. There are questions of how do you establish that initial bond? How do children communicate their needs when they're very tiny and can barely do anything? How do parents negotiate the different duties that they have? Who's going to do what? How is it going to all work? Well, what better organism to study this in than poison frogs? Yes, poison frogs. It turns out that they have been studied for decades and their behaviors are well understood. The tadpoles are see-through so you We can see what's happening physiologically, and we can make chemical measurements about both the parents and the offspring to understand the chemicals that are driving the parent-child relationship.

3:24Lauren O 'Connell is a professor of biology at Stanford, and she specializes in studying parenting chemistry between poison frogs and their offspring. Lauren, what led you to choose poison frogs as a major organism of attention for your basic research in biology? Yeah. So the reason I chose poison frogs was because they show a variation in behavior, social behavior and reproductive strategies that is kind of unparalleled among vertebrate animals. And so I was really interested in the neural mechanisms of social bonding and bonding between parents and offspring and how it's decided whether mom or dad cares for offspring.

4:09So I was looking for a system where mom cares for offspring or dad cares for offspring or both or nobody. And that led me to poison frogs. They were kind of the only option for this behavioral diversity question that I had. Okay. So there's a few things I have to ask before we get into all the interesting stuff that you just alluded to about parent offspring relations. And the first thing is, is it dangerous to work with these frogs? No. Oh, well, I don't work with any that could kill me. This is a promise I made to my family. And so they actually get their toxins from their diet. And so all the frogs we have in the lab are non-toxic, unless we're like making them toxic on purpose to study that process.

4:57And then in the field, like we use like gloves and things like that to like to handle them. But they wouldn't kill you, they might make your, if you decide to lick them, they might make your tongue a little tingly or they might make you throw up, but you would not die. Okay. This is really important. And otherwise everybody would be worried about this for the entire conversation. So thank you. So let's get into what you alluded to, which is this really interesting behavior about an opportunity to study the bonding of parents with offspring. What are the questions that you can ask in these frogs and what makes them.

5:37So one of the things you pointed out already is that there's a huge diversity of them. So you can probably find in different biological niches, you can probably find different strategies. How do you approach this? How do you wrap your head around it? What are some of the experiments that you do and what do you learn? So that's about seven questions. I apologize. Yeah. Well, we take two approaches. One is a comparative approach across species. And we're trying to figure out like why in some species only dads care for offspring and on some species only moms do it and is there like any general themes across species that are like signatures of parenting um and then the other is like within a species there's a lot of variability and like the care that parents put into their their kiddos and things like that and so we also look at like individual or family variation within a species so we have this both comparative aspect and this like kind of deeper kind of question about plasticity.

6:35Is it easy to tell when a parent is caring for one of its tadpoles and when it's not? So it seems to me you have to define a lot of things in order to make progress. Yeah, yeah, yeah. Well, the beautiful thing about the system to me was that they've been a model system in ecology and evolution for a really long time. And so their behavior was really well worked out. It's just that no one had done anything molecular, no one had looked in the brain before. And so that's what I decided I was going to do. So the behavior is really, really well worked out. And it mostly, so they lay there, I'll give you like a brief overview.

7:19This is what we want. Yes. Yeah. Because when you think of good parents you don't think of frogs and so this like hopefully this next three minutes will change that um and so they i hesitate to tell you who i do think of and don't think of when we talk about so let's just move on yes yeah um and so they lay their eggs like on the leaf litter and the rainforest floor and dad takes care of them and then um either mom or dad depending on the species will transport their tadpoles piggyback style because when the tadpoles hatch they're still aquatic and so they need to make it to water somehow and so their parents will transport them either one at a time or in batches like with a school bus kind of method um and then and then they place them in these pools and then in some species there's they have this like really extended care where moms will come back and feed them these trophic unfertilized eggs like throughout development.

8:18So like every day they'll come and check on them, give them food. And this happens for like two months until the tadpoles complete metamorphosis and walk out of water. So it's a really intense period where they put a lot of energy into their offspring and individual care. Do we have an idea? You said that there's a lot of variability and you're interested in the molecular basis. Have you been able to identify the sources of these variability? So one thing that I had to ask is, you know, in the human literature, people talk about oxytocin. And I don't even know if frogs have oxytocin. But is the expectation that they will be similar molecules or are you expecting big surprises?

9:00Yeah. So it's thought that oxytocin is involved in parenting, kind of co-opting this maternal circuit of lactation in mammals. And so, you know, frogs don't do lactation. And so we've tested this idea of whether or not oxytocin is involved in parenting, and it doesn't seem to be the case. What seems to be the case, at least in our frogs, and what kind of we've seen creates this variability of how much you bond to your babies is variation in endogenous opioid signaling. So this is like something that kind of reinforces your interactions with your offspring as a rewarding experience or not. And so like high care families where they put a lot of investment into their tadpoles, they find it a very rewarding experience.

9:52And a lot of like opioid stuff is happening in their brains. And then like low care parents, they don't seem to find that as like a reinforcing or rewarding behavior. Wow. Wow. And I know that you've also written a lot about sex hormones, testosterone, estrogens, and similar. Do those play a role? I mean, I guess I assume that there are male and female frogs, I think. Yes, that is true. But you said that there are very different strategies. Does that modulate the levels of these chemicals? How do they figure into these, if at all? Yeah, well, that's a good question. And I don't know if I have the exact answer for you.

10:38What we do know is that the same kind of brain regions and neurons are turning on whether or not it's a male or a female who's performing care. So there seems to be this core kind of circuit for parenting. And hormones might toggle them to be more or less active in each sex. But there seems to be this kind of core parenting pattern. Um, but like in our frogs, just like in human males, like testosterone goes down when you become a dad, um, when they're, uh, when in monogamous species, they have these correlated levels of hormones. So in humans, you know, in, in like married and in people who are in love, they tend to have like correlated levels of hormones and our frogs that are pair bonded do that too.

11:24Um, and so similar levels of similar patterns are happening with hormones in these relationships as we see in human families. And so you mentioned humans, and I was being very careful because part of what you're studying is just to understand and discover how these things work. And it's not always about learning things for human application. But since you mentioned humans, can you tell me how do you approach this work? Is there a distant hope to have this be relevant to humans? Or is that really not the point? It's like, how is nature doing these things? What are the options? What's the diversity of approaches?

12:02Yeah. So for sure, frogs and humans are very far apart. And so we're not like seeking to cure a disease here. What we're trying to learn is like the basic blueprints of how parenting happens, like and is reinforced in the brain and how social relationships are reinforced. And we think, you know, we've been working on frogs. I think they're a good system because they have these like complex family relationships that you don't see in a lot of like traditional lab model systems. And they have like a very simplified brain, you know, not as many neurons. It's a little bit easier to understand what's happening.

12:44Yeah. Because just like there's, it's a little bit more of a simple system, you know? And so like for us, we're trying to address this basic question. And if like insights come out of it, then this is something that can be tested by others and more like complex animals to like, have like treatments for, you know, things that are related to like opioid signaling and parenting, like postpartum depression or something like that. So I think, you know, there are several steps that go along that. But I mean, we need to understand this like basic building, like the basic building blocks of what's happening before we can understand how something like breaks in a disease context.

13:22Great. Great. Thank you. So looking at the work that you've done on parent-child relationship, it's so rich. And we've talked a little bit about bonding and some of those chemicals, but you've also looked at teamwork and coordination between the parents and communication. So can you tell us how that work proceeds and like, what are we learning there? Yeah. So, well, what we've mostly paid attention to is the role of, or what's happening in offspring, because it's very easy to do experiments in adult animals, especially in mice, you know, there's a lot of really lovely work there. But it's, it's a little bit harder to understand what's happening in the offspring.

14:01And so the reason we think that they're useful, the tadpoles that we study is they have this really robust behavior where they have to recognize their parents when they come to visit them, and they have to communicate that they need food. And so they do this with this like little dance behavior, their mom like comes in, and then the tadpole is like, Oh, that's my mom. And they recognize her based on smell. So they can smell their mom versus and tell her apart from not mom. And then they're like, Oh, this is my mom, I need to tell them I'm hungry. And so they do this little dance behavior. And so we've been able to work out like, Oh, the you know, the tadpoles are recognizing them by smell, then this activates these neurons which then activates this circuit and then this is how like if we turn on this neuron then this is how this tadpole communicates that it needs food because we don't understand a lot about how you know communication and uh kind of parental recognition happens in the infant brain and so we've been able to work that out in tadpoles and you know now people have a blueprint of what to look for in other organisms like mammals.

15:10It is very charming to think about a little child, a little offspring dance. And I can imagine I've seen some of that myself. So on this issue of the communication, I know that one of the experiments you did is take a gene that I believe was implicated in human autism and put it in the tadpoles or mutated it or did something to it. Can you tell me about that? And how does like introducing a gene or mutating a gene affect the dance, the recognition of mom, the whole shebang? Yeah, yeah. So we started working on this gene called FMRP. So it's a gene that is most often linked to autism. It's like if you could pick one gene for autism, you know, autism is a single, is a multi-gene, you know, trait.

15:59But if there was one gene that's most often associated with it, it would be this gene, this fragile X gene. And so what we see is that when tadpoles are doing this communication behavior, that the neurons containing this gene really ramp up and kind of turn on. And so when this gene is mutated in humans, you see these deficits in sensory signaling or in communication and things like that. So it creates a lot of variability in sensory motor behavior. And so we were curious then. We were like, okay, so we want to understand how this gene might be regulating this behavior in our system. And so what we do, you know, tadpoles, the nice thing about tadpoles is they're kind of still squishy and they're transparent.

16:48And so you can look at them, you can see the brain, just by like looking through them. And then you can also like, inject some genetic constructs or more felinos to either express genes or turn off genes, and then ask, you know, and then wait a couple days and then ask, like, okay, do you still know who your mom is? Like, do can you still communicate that you need food? And so these are kind of how experiments go. And so when we knock down some of these genes, like, for example, when we knock down the ability to make dopamine or knock down, you know, some autism associated genes, then we see that they can't coordinate their behavior as well.

17:26Or they tend to like, you know, beg to everybody instead of just their parent, you know, like, so some of the this like, kind of the ability to distinguish between individuals sometimes, sometimes goes away. And so these are kind of experiments that we do to test the role of a specific gene in behavior. So as a side effect of this answer, you told me a couple of really interesting things. So they're see-through, which now it becomes clear why it would be very attractive for you to study because certain things become much easier. How big are they? Because you're now injecting, you said you were injecting like basically biological reagents.

18:05I guess I don't know how big tadpoles can be. I guess they start out very small, but can you give me a sense of the size ranges we're dealing with? Yeah, their body is somewhere between half a centimeter to a centimeter, you know, and then they have a tail that's like two to three times about that. So, yeah, they're transparent. And so then we can look at things like, you know, we can inject them with a dye and watch their neurons like go on and off while they're, you know, we're giving them the smell of their mother versus their not mother and things like that. So we kind of treat them like a zebrafish, except we study these behaviors, which are also see-through when they're larvae, exactly.

18:45And so, but then we study these kind of central behaviors that are important for family relationships that aren't seen in other organisms. I just have to ask, are they aware of their siblings? Or have you studied the sibling interactions versus like, you're not my sibling, we don't have the same mother. I could imagine there's stuff there, but I don't know if you've gone there. So, well, this is important because the species that we study, they put their tadpoles in individual pools. So each tadpole has their own nursery. And this is important because they are cannibals. And so if a parent ever puts two of them together, there will only be one.

19:27Oh, my goodness. A day later. So they are intense about defending their resources. They don't allow each other into each other's bedrooms. You know what I'm saying? And this is even the siblings. Even the siblings. Even the siblings. I think some other people have shown that they're like the late, the time at which it takes them to like show aggression will decrease when it's a sibling, but it still happens. Well, and we're all going to just quietly ponder that. And as I say, this is the future of everything. I'm Russ Altman, and we'll have more with Lauren O 'Connell next.

20:20Welcome back to the future of everything. I'm Russ Altman, and I'm speaking with Lauren O 'Connell from Stanford University. In the last segment, we learned about these fascinating poisonous frogs and how they can be used to understand parent-offspring relations. In this segment, we're going to hear about a special apparatus that Lauren and her lab has developed for tracking frogs. They're actually wearing these little pant speedo things that allow the lab to track them over a kilometer as they find home after foraging. In addition, we're going to hear about how those poison frogs prevent themselves from poisoning themselves.

20:54If you're carrying around a bunch of poisons, you might want to make sure that you don't poison yourself. Lauren, I wanted to ask you about a fascinating set of experiments that you're doing on understanding how frogs kind of understand their physical environment and how they go out foraging and then get back home. And you've done something quite remarkable in terms of instrumenting these frogs. Can you tell us about that? Yeah. So we, because our frogs are really good parents, they leave their babies in these little nurseries throughout the forest. and they have to remember where they put their babies because they have to come back and feed them.

21:32And so what we were curious about is how do you remember like where this exact thing is in a very complex environment, like a rainforest? Yeah. And so we were trying to figure out how they recognize where they are and if they're displaced, how they find their way home. And so the frogs though are really tiny. And so, you know, usually you would like stick a GPS on something you know like like because if you wanted to like look to see what a whale was doing but these frogs are tiny and so we developed these like kind of frog pants or like a frog kind of speedo situation it's kind of like a g-string and it has this like string coming off that we can detect with an antenna and so the frogs can kind of go about their daily lives and then we can keep track of where they're located as they're moving around and so what we do is we like figure out where home is for them.

22:28And then we move them, you know, some amounts of distance. So the farthest we've moved some frogs is over a kilometer. And they like sit there for a moment. And it looks to me like they're getting their bearing. I don't know what's actually happening. Are they looking around? They kind of like look around and they kind of sit there for a moment. And then they like take off and they beeline straight to home. It looks like they're like trying to figure out what to do and then they make a decision and then go. And so, and then we track them like over several days and like trying to see like how they get home.

23:06Some individuals are really good at that and some aren't. And so we're trying to figure out like, you know, what, how they're able to do that because, you know, they don't have very many neurons compared to a mouse or a bird, but they're able to get home from a kilometer away so how does that happen and this is even when you've placed them there so it's not a question of them replaying how they got there and undoing it no no because they can't see where they're going so we like carry them around in a bucket with a magnet so just in case they're like paying attention to the earth's magnetic fields and so then they like we just place them somewhere and they just have to like figure out where they are and figure out what direction home is in.

23:49And I would have a hard time doing that. I don't have a good sense of place. Okay. So there's two things I have to ask. The first one is just about the physical setup here. So I imagine that these have to be very light and they probably don't even carry their own power. Are they passively powered or do they carry it? Yeah. They're passively powered because it's kind of a animal ethics issue. We don't want weigh them down very much. They still need to be able to forage and mate and take care of their offspring. And so what we have to do is make a passive antenna and then we go around with a receiver and try to locate them.

24:32Great. And then the second question, which, and it refers to the comment you just made, have you studied and are there differences between male and female frogs in their abilities to do this. I think you've written about this. And what have you found? Yeah. So we were curious about this because there's some sex differences in mammals. And so we wanted to see that, you know, that it's proposed to being like tied to parenting and to like roaming around for resources. And so we wanted to test that because different parents have different responsibilities in these family structures. And so what we found was that usually male frogs were better at navigating home than female frogs, kind of regardless.

25:17And so it kind of gave support to this idea that has been around for a long time and has been found in mammals that having testosterone around kind of changes the hippocampal function and makes some types of spatial tasks a little bit easier to accomplish. Wow. And, and well, that's interesting. And I can imagine fraught when you, when you, when you announce this. And so you have to be very careful, I'm sure about like bounding the, uh, the, what you did and what it means and, but very interesting. Oh, okay. So because, um, we don't have a ton of time and the, I, the, the homing behavior is just really fascinating, but I do want to move to another thing that you've done, which is, you started the whole discussion talking about that these are poison frogs and we're glad that you and your lab are safe and that may be a little tingling.

26:08I think you said if you're kissing it or something, but they have to deal with this toxin as well. And so, and I know you've studied the mechanisms by which these frogs tolerate carrying around what's essentially a bunch of poisons. And what have you found there? Yeah. So they can carry around a lot of different toxins. and so there's been a lot of studies in like newts and snakes for example puffer fish that have like a really potent toxin and they have and they have a mutation in their ion channel that gives them some resistance um this isn't that's not how it really works in the frogs because they have so many different kinds of toxins and they're just kind of getting them all from the environment so you kind of don't know what you're going to get so there so it sounds like they're like opportunistic toxin collectors yes yeah yeah exactly and they get it mostly from like the ants and mites that they're eating.

27:00And so we wanted to figure out how they were doing that. And what we found was that they've evolved this kind of toxin sponge protein that binds a bunch of different toxins that would be lethal at, you know, at similar doses to people. And so, and it even bought, and it's a very like promiscuous binding sponge. So it like binds a lot of different things. And so this was really interesting to us because it was a new protein that they kind of like, you know, that kind of evolved in this clade. And it has like very broad functionality. So it binds things, you know, like cocaine and like other toxins that can cause like a bunch of like overdose issues and in other species.

27:44And so to us, this was really exciting because it provided a mechanism as to like why they can take up all sorts of different things from their environment without making themselves sick. And can they control? So this is a protein and you said it's kind of like a sponge. But can they release then? How do they do the release or how do they manage then using it to protect themselves or their offspring? Yeah. So I think it protects their own nervous system. And then the toxin is stored in these glands in their skin. And so when we go to the field, it's called milking them. We milk them for toxins and it's you kind of like rub their back and it's kind of like this like milky white substance that's released it kind of smells um and so you know because they're not just like releasing toxins into the environment at all times that's a waste right um and so we like milk them for their toxins like you know do a toxin collection and analyze it uh later in the lab um and so the protein i think is just what we think is it's it's there to protect them from getting sick and it's not really involved in the delivery process.

28:53And, and when you, so, and therefore when you analyze this milk, you're not seeing huge levels of this protein in that, in that fluid. No. Um, and, and so I just have to ask, um, you said ants. So just tell me a little bit more about where these toxins come from. I mean, we know that like, especially like in the Amazon, there's this image of like, it's a, it's a battle between organisms for survival. And that, and we, and as you know, there's a lots of drugs that have been described, human disease drugs, that have been discovered based on looking at these molecules that are basically part of the warfare between bacteria and fungus, and I guess frogs too.

29:28How diverse are these molecules and where do they come from? And what is their typical mechanism of action? How do they kill each other? Yeah. So this is tapping into a very ancient system from, as you alluded to, mostly from plants and from microbes to release compounds to protect themselves from predation. So like plants and herbivores and, you know, and then like microbes and, you know, there are other like microbial interactions and things like that. And so what we think is that there's this like trophic chain or like this relationship and a healthy ecosystem that passes on these molecules from microbes and plants to the insects that the frogs are eating to the frogs themselves.