In 2016, while looking for a new interviewee for the blog, I ran across the website of a research laboratory at the University of Texas, Austin. I checked out the website, looked at a few of the lab’s publications, and it became quickly obvious to me that the lab’s director, Dr. Hans Hofmann, was someone I needed to interview.
I reached out to Dr. Hofmann, introduced myself, and asked him if he would be interested in doing an interview for the blog. He replied within a couple of days and happily agreed. We began the interview process, but work caught up with him, and we weren’t able to get it completed. So fast forward to the present, and we did a complete reboot of the original interview.
Since receiving his Ph.D. in biology from the University of Leipzig in Germany, Dr. Hofmann has received numerous fellowships and awards for his work at the University of Texas, Stanford University, Harvard University, and the Marine Biological Laboratory in Woods Hole, Massachusetts. In addition to running the Hofmann lab at the University of Texas, he has served as Director of UT’s Center for Computational Biology and Bioinformatics and UT’s Center for Biomedical Research Support. He has given over 130 invited keynote lectures and seminars but has also given numerous public outreach presentations.
Needless to say, getting Dr. Hofmann to take time out of his busy schedule to answer a few questions with me was a real bonus. Outstanding stuff ahead. Buckle in!
What intrigues you so much about cichlids to want to study them?
Well, cichlids are amazing animals. They are incredibly diverse. There are more species of cichlids out there than any other group of teleost fishes. And as you know, teleost fishes make up more than half of all the vertebrates that are currently alive on the planet. Cichlids are diverse in a lot of different ways: They have different colors, they have different behaviors, they live in a lot of different environments. This diversity allows us to ask a lot of questions about how their physiology and behavior adapt to different environments, how they make decisions about who they want to mate with or where to set up spawning sites, who they engage with in an aggressive interaction, and so on. One thing that is really intriguing about them is that they do all of this before our eyes. It’s not that difficult to observe this because we can put them in a reasonably well set up aquarium. They will acclimate quite quickly and do well, and show a lot of their natural behaviors there in our living room or in our lab.
Your cichlid research largely focuses on specific mechanisms that underlie social behavior. Perhaps you can briefly share with the readers more detail about this.
My laboratory is interested in two major questions. First, we want to find out what the brain actually does and what goes on in the brain when an animal shows social behavior, such as aggressive behavior, parental care behavior, sexual behavior, or cooperative behavior. We find all these kinds of behaviors in different forms in cichlid fishes. We go about this research in a number of different ways. One way is that we look at neuroendocrine mechanisms. For example, those that involve sex steroid hormones like testosterone or estradiol or these peptides, vasopressin and oxytocin, that you may have heard of because they’ve entered into popular culture – although most everything you’ve heard about them is probably wrong.
The so called “love hormone,” oxytocin and the “fight hormone” vasopressin, which is quite misleading. But that’s how these things get marketed. If you Google oxytocin, you can actually buy a vial and apparently that will help your romantic pursuits…or not. So those are some of these pathways we look at. What we find is, whether we look in cichlids – or other people have looked in birds or in mammals, including humans – that these pathways seem to be highly conserved in their role of regulating social behaviors. Such as, for example, in a monogamous species where a pair-bond is formed, oxytocin and vasopressin seem to play an important role in regulating pair-bond formation and social affiliation more generally. Whether we talk about a cichlid, whether we talk about a songbird, or whether we talk about a small rodent or possibly a human as well. I might come back to this later, but that is an important insight. It also kind of shows us that we can use these fish as a model system to understand better what’s going on in our own brains. We can do a lot of these experiments in a fish that we can’t do in a human for obvious reasons.
The second big area of research in our lab has a more evolutionary outlook. We take this insight that I just mentioned, where it appears that the role of some of these hormonal pathways is highly conserved across vertebrate animals, and study it in a more systematic way using genomic approaches across many species of vertebrates. Our largest study thus far included 88 different species of fish, frogs, reptiles, birds, and mammals. We ask to which extent, on a much larger scale, the processes that occur in our brain that regulate social behavior might actually be similar or conserved. As it turns out, there seems to be a remarkable amount of conservation, suggesting that our last common ancestor, who lived about 450 million years ago, already had a lot of this machinery for social behavior built into their brain. What we’re seeing out in the natural world is really more of a variation on a very old theme, if I want to use this musical metaphor. It’s not really something that is always a new feature or a new way to do it. It’s really fairly old. It’s relatively small variations. So that’s kind of what we what we do in a nutshell.
A considerable amount of your work focuses on the species Astatotilapia burtoni, a beautiful little haplochromine mouthbrooder from Africa. What makes that species a good model for your research?
Burton’s mouthbrooder, as A. burtoni is called colloquially, is a really amazing cichlid. It’s no longer as popular in the hobby as it was in the 1950s and 1960s, especially in Europe. But it’s been in the aquarium trade for a long time or maybe it’s coming back in from a scientist’s point of view.
This fish has a number of really unique advantages. One is that they have a fairly short generation time – in our hands and our lab about 3 to 3.5 months – and they are incredibly robust. You can do all kinds of things to them and they will breed happily and show their natural behavior. They live in social groups that we can manipulate very easily and that we can monitor in a quantitative way in our aquaria.
Another fascinating aspect about A. burtoni is that they are maternal mouthbrooders, so the female will incubate the eggs in her mouth for a couple of weeks after they get fertilized and then further take care of the offspring. What’s interesting about the males is that they come in two different flavors where they’re either socially dominant, brightly colored, with large gonads, and very aggressive, which allows them to acquire and maintain territories. Or they’re fairly dull in coloration, they don’t really show a lot of these aggressive behaviors, they have tiny little gonads, and usually don’t reproduce. Importantly, they can switch back and forth between dominant and subordinate states, indicating that they’re incredibly plastic, as we say. And it’s this plasticity, this change between being socially dominant and drastically different when they are subordinate, that has caught our attention.
We use these fish as a model system to get at the brain mechanisms that allow these animals to show these vastly different behaviors. The same animal, a week later or even just an hour later, may be a very, very different animal in terms of its behavior, in terms of its appearance. So we’ve made a lot of progress there. And that’s really what originally got that research started. Much of the original work was done by Russell Fernald at Stanford, who I worked with when I was a postdoc. And then I took the system with me to explore many other questions.
Many cichlid keepers don’t realize that fish utilize numerous cues, both physical and chemical, to send various behavioral signals (e.g., “don’t bother me,” “I’m ready to breed,” “I’m sick”). Perhaps you could discuss some of these cues and how they work.
I did hint at it earlier that one reason cichlids are so attractive, not only to us researchers but to the hobbyist in general, is that they are highly visual animals. That has two consequences. One is that they use color for signaling to each other, but of course we see that color as well and we’re intrigued by it. We find it aesthetically pleasing or fascinating. The other reason why that is helpful to us is that much of what they do consists of visual displays that we can easily observe, measure, quantify, and so on. If cichlids mostly communicated by chemical or olfactory cues, like what a rat does for example, I don’t think they would be as popular in the hobby.
So visual cues are clearly very important, and much of the research on the sensory side of these fish, and cichlids in general, has for a long time focused on visual communication, the role of the different color markings, the information that they convey. For example, in Astatotilapia burtoni, the red shoulder patch is important for aggressive signaling as is the lachrymal stripe, or eye bar, as we call it. There’s a lot of classic research on these visual signals in this as well as in other species of cichlids. But more recently, I would say over the last 10-15 years, we and others have paid more attention to other sensory modalities as well, including chemical signaling and mechano-sensory signaling. I can give you a couple of examples.
We’ve done some studies where we have used steroid hormones or their metabolites that the fish release either through the gills or when they urinate or defecate. And these metabolites can often be sensed by other individuals through the olfactory epithelium in their nose. They can serve as signaling molecules that indicate the social rank or reproductive state of an animal. An increasing amount of work has looked at that. More recently, Dr. Karen Maruska’s group at Louisiana State University has done some beautiful work on the role of the lateral line, which is a mechano-sensory system that runs along the left and right side of the fish, and which allows them to detect pressure waves in the water. You can think of it like vibrations of a sort. Karen’s research has shown that this also has a very important communication function in A. burtoni, between the males in particular.
And finally, we have not done any of this research, but work by several other labs has shown the importance of acoustic signals in cichlids. Cichlids make different kinds of noises. They make them in different ways, for instance, with their swim bladder or with their jaw. There might be other mechanisms as well. This acoustic signaling has an important function for mate selection. Females seem to evaluate these sounds that males make in mate selection, but they also seem to play a role in male-to-male aggressive interactions as well. As it turns out, these fish produce a kind of a symphony of signals, of which we only perceive one part of it. By only paying attention to the visual signals that we can see in the aquarium, we really only hear the violins of this entire symphony. The violins are important, but it’s not the whole thing. So that’s kind of how I would describe it.
So let’s discuss chemical stressors for a second. Serious hobbyists are in tune to environmental stressors of their fish (i.e., water parameters). Such parameters as pH, temperature, ammonia, nitrite/nitrate concentrations and hardness. Is there any evidence to suggest that these might affect certain behaviors differently?
Well, there are two ways to think about this question. On the one hand, each animal has a particular window, if you will, of these environmental parameters where it’s happy, where it’s comfortable, shows well-being, and so on. But as soon as you push it in one direction or the other, and parameters get outside of this zone, problems can occur. Animals have different ways to respond to such a situation. They can try to avoid it by moving somewhere else, if that is possible. Or they can try to physiologically acclimate to it, which is possible to a certain extent. Or they might get sick and then show sickness behaviors. There is a whole area of study in behavioral neuroscience that looks at sickness behavior and the underlying neurobiological mechanisms of that. It’s not something that we study. When the environmental conditions get too far out of this zone, the animals just get severely sick and knocked down and might eventually die.
I think what you’re asking about is a slightly different approach to that. Can very subtle variations in these parameters influence behavior, such as social behavior, in a specific way? I’m not an expert on that. There may be more known than I know about this. But I don’t think it has been studied as much in detail, i.e., how fairly subtle fluctuations, say pH or temperature, might affect particular behaviors. Not in a way that the animal gets sick, but how it might change its behavior just a little bit. I think there’s an opportunity here to do more research. I do want to mention, however, a couple of examples.
One is carbon dioxide (CO2), which you didn’t mention. I mention this because of course it’s related to other gases that are dissolved in the water. There is increasing evidence, particularly in marine fishes where most of that work has been done (not so much in freshwater fishes), that increasing CO2 concentrations can actually affect foraging behavior, orienting behavior, and apparently also reproductive behavior in a variety of fishes, quite strongly. Increasing C02 concentrations in the ocean are a direct consequence of the increasing CO2 concentration in the atmosphere from burning fossil fuels. A lot of that CO2 gets sequestered into the oceans, which are really huge reservoirs. As it turns out, even relatively small changes in CO2 concentration can affect behaviors. So this is kind of an interesting and active area of research.
Another example I want to mention, because you do mention pH, is that sex determination is very complex in cichlids and in fishes in general. They don’t necessarily have sex chromosomes the way we have them. There are sex chromosomes in some cichlid species, but there appears to be a lot of flexibility not only across species but also within species. Importantly, there are also environmental factors that determine whether an embryo develops into a male or female, and one of those environmental factors is pH. A slightly higher or slightly lower pH can bias whether eggs develop mostly into males or into females in a number of species. There’s clearly a lot that these water parameters can affect. But to which extent relatively subtle variations, that we would tolerate in our aquarium systems and wouldn’t be a problem for the fish, per se, might affect behavior in more subtle ways, I don’t think is well understood.
One of the best aspects of cichlids is that they often exhibit very individual behavior. You were involved in a recent study of A. burtoni that suggests early socialization of fry is one factor that can and does impact aggression in adulthood. Can you summarize that study and its findings for the lay person?
This is a study that we just published in the journal Hormones and Behavior. The first author is Dr. Tessa Solomon-Lane, who until very recently was a postdoctoral fellow here in my laboratory at UT Austin. She is now an assistant professor at Claremont McKenna College in California. This study was actually our first foray into trying to understand how an early life experience might affect behavior later in life. We know that early life experiences, especially adverse experiences, can affect health and well-being later in life. That’s been documented fairly well in humans. But how it actually happens, what the mechanisms are, is not well understood at all. We needed a model system where we could study these kinds of questions, and we thought our fish might be a good model system for that. However, we had to do some groundwork first.
I’m going to just touch on a few high points of what we did in that study. One thing is that we would either remove the fry from the mother’s mouth a week after fertilization or we would let them go for the full, 2 to 2.5 weeks that the female would normally incubate them. Thus, we have two groups – a short and long incubation. And then we would raise these two different groups, either as pairs (only as two fish) or we would raise them as groups of 10 individuals. This is a profound difference in social context. So, if basically for your entire developmental period you grow up with only one other individual that you interact with or with a whole group, what actually happens?
As it turns out, there are profound differences in their behavior in terms of how they interact, their ability to form dominance hierarchies, and how stable those dominance hierarchies are. Those seem to be severely compromised if they grow up only as a pair as opposed to a more natural group.
Then we looked in the brain. We looked at the activity of particular genes that are representative of some of these pathways that I’ve mentioned, and also one that we haven’t talked about yet – the glucocorticoid pathway or stress pathway. That pathway is important in producing and responding to cortisol, our stress hormone. What we found was that in those individuals that were reared in groups, they had a highly integrated gene network, if you will, that appeared to function in a very coordinated fashion. Whereas it was very disintegrated and disorganized in the individuals that were raised as pairs. This is a fairly severe difference that has key consequences for the activity in the brain and for the behavior of these animals later on. But it’s not as severe as what is often done in these kinds of experiments where animals are raised in isolation, which is not particularly natural and may just be too extreme a situation.
So that’s largely what that paper was about, and it forms, from our perspective, a very good foundation. Now to explore in more detail some of the questions that came up – the role of the stress axis in early life experience. How does it actually do that? What are the mechanisms that lay down, if you will, this kind of memory from the early life experience that affects the behavior and the gene expression later in life? There are a lot of interesting questions that have come out of it and Tessa will continue to work on that in her laboratory with her students.
With regard to mate selection, are there any findings from your work with A. burtoni that might apply to other cichlid species? If so, can you explain?
Yes, I think so. Mate choice, mate selection, is a topic that we have dabbled in a little bit, not in recent years, but we’ve had a few papers in the past, especially when Dr. Michael Kidd was a postdoc in our lab. Michael’s an interesting fellow because he came to this kind of research starting out as a cichlid hobbyist when he was a teenager. I can tell you that my fish facility was never in better shape than when he was in the lab. He did a series of nice experiments looking at how females make mate decisions in terms of which male they should spawn with. What he discovered, and did some nice work on, was the important role of a specific prostaglandin, small molecules which are generally thought of being important in immune response, blood pressure regulation, and so on. But these molecules have other roles as well. For example, across vertebrates, prostaglandins are important in egg maturation in females (and, in mammals, inducing labor). What happens in a cichlid, and other fishes as well, when the female’s eggs mature, a lot of a specific prostaglandin, prostaglandin F2 alpha (PGF2a), is released into the blood stream, and some of it gets into the water through both the gills and genital opening. That has two consequences.
Within the female, and Michael showed this, if you treat a non-reproductive female with PGF2a, within minutes she will show an interest in males that previously she did not show because she’s not gravid, she doesn’t have any mature eggs. Why would she show any interest in a male? But she does when treated with PGF2a, one of the strongest behavioral responses I’ve seen to date in my entire career. It was remarkable.
And the other effect it has is that the PGF2a that is released into the water gets the males really excited, and the males will orient towards that source of the PGF2a. If there is a female there, whether she is gravid or not, they will start courting her. In fact, they go through all the motions of spawning behavior with a non-reproductive female that is treated with PGF2a. The female will visit the bower, go through all the spawning motions, pretend that eggs are being laid and get fertilized and picked up in her mouth, even though nothing like that happens. There are no eggs that can be laid, but they go through all the motions. It’s truly remarkable, and it provides a window into what PGF2a does in the brain. So that seems to be an evolutionarily conserved mechanism that we find in other cichlids as well.
The other thing I can say that seems to apply in our species and many other cichlids is, again, as I talked about earlier, the combination of different sensory modalities. They pay attention to not only these visual cues that we can readily see, but also to chemical cues and to these acoustic cues that I mentioned. And that seems to allow them also to tell the difference A) between the species as well as B) between, let’s say, attractive partners and not so attractive partners.
Can you talk about some other interesting discoveries with regard to decision making in this species (A. burtoni)?
I have one story that I’m still fascinated by, although it’s been a couple of years since we’ve done this work. This is work by Chelsea Weitekamp, when she was a doctoral student in our lab. She graduated three years ago, in 2016. It was truly remarkable. Chelsea came to my lab with a behavioral ecology background. She had never done any neuroscience or molecular work. She came to me and she said, “I’m actually interested in cooperative behavior and how animals work together to achieve a particular goal.” I said, “Well, this is really interesting, Chelsea, but our fish don’t cooperate. You know, they are mean to each other. They fight a lot and all that.” And she said, “Well, I don’t think so. I think I can get them to cooperate.” And she did! It was quite amazing. If I would have thought about it, I would have realized that her idea actually makes a lot of sense.
What she did is she looked at the literature. She realized that there has been this longstanding idea that males set up these lekking aggregations, which are basically small display territories where they display to each other and display to the females that come through. This is something that you see in a lot of different species in birds and fish and so on. And frogs of course, like in a frog pond, where they hold neighboring territories and enter into some sort of a gentleman’s agreement. They don’t fight all the time, which would be very distracting and would keep them from advertising to females. Yet they still have these ritualized displacements toward each other such as “This is my area, this is yours. Let’s just respect this boundary and keep the peace here.” That is referred to as the “Dear Enemy Effect,” which was postulated decades ago that. If that is the case, it would actually be in the interest of a particular territory holder to come to the aid of a neighbor that gets invaded by an intruder. This is because, if the intruder kicks out your neighbor, then you have to renegotiate all these agreements from scratch, and you might actually be at risk of getting kicked out as well. So you might as well help your neighbor. Chelsea set up a beautiful paradigm in the laboratory where she tested this question because there had been very little compelling behavioral evidence that this really happens in any species. The best work we could find was in fiddler crabs in Australia. Beautiful work. But there was no neurobiology. So what Chelsea showed was that they indeed enter into these, what we call, cooperative defense or resource defense coalitions. The neighbor will come to the aid of the resident that gets intruded upon and show aggressive behavior. But if you only look at the behavior, it’s actually really, really difficult, even if you do very sophisticated experiments, to discern whether the neighbor is really coming to the aid of the resident, or whether he’s just defending himself because he’s afraid that he might lose his own territory as well. What Chelsea did is she looked in the brains of these animals. She did this in a particular way where she could look at the activity patterns of different regions of the brain that we know are important in social decision making, in regulating social behavior.
We call this the “social decision-making network” of the vertebrate brain. Chelsea used a molecular technique to visualize this activity. When you do that, you find that the activity pattern in the resident is fundamentally different from that in the neighbor in ways that make sense to a neuroscientist. But it’s also in a way that makes it very clear that the neighbor is completely “aware,” if you will, that his role in the cooperative defense is different from the resident’s. This result is one of the very few examples where anybody has looked at the neurobiology of cooperative behavior, which seems crazy given how important cooperation is to us humans.
In cichlids, their cognitive abilities are through the roof. They are amazing animals. I mean they do things that, even when I was a student or a postdoc, people maintained only primates can do. We’ve found a few bird species that can do them, and cichlids can do pretty much all these things. They are really remarkable.
I’ve always felt that traditional ecological knowledge (derived from hobbyists and, say, long time fishermen) and scientific ecological knowledge (derived from scientists and researchers) can complement each other. I call this experience versus experimentation. What ways can you see hobbyists contributing to the landscape of discovery that is often confined to science?
This is a wonderful question and one that I have thought about quite a bit. I’ve been involved in a lot of public engagement activities. The postdoc I mentioned earlier, Dr. Tessa Solomon-Lane, and I actually developed a workshop here to train scientists, particularly graduate students and postdocs, in public engagement techniques. Not the old farts like me, but young people, to become better at engaging with the public. One important aspect of that is what one might call citizen science. There’s a lot of activity now, also from a science communication point of view to understand better what citizen science is and how we can get interested audiences like hobbyists, for example, more involved and also into contributing in a meaningful way. Now the birding community has been doing that for more than 120, 130 years in some countries, quite well but also in a somewhat limited way. I think there is a general acknowledgement that this back-and-forth, what you call this interaction between experience and experimentation, is important. There is a lot of potential there, but nobody seems to quite know how to best go about it. I think one way to do this is to kind of develop questions that are amenable to both approaches.
There’s this fellow at Sacramento State University in California, Dr. Ron Coleman, who years ago started the cichlid egg project where he would have hobbyists send him eggs from all kinds of different cichlid species. He then measured them, he did a number of different assays on them, and then he tested different kinds of evolutionary hypotheses that might explain the variation excise. That was interesting, but it was never publicized in a broad way. We have thought about this in a slightly different way and that is realizing how many different species of cichlids are out there in the hobby. Our interest in social dominance and territorial behavior is to basically come up with a questionnaire that we could share, for example, with the membership of the American Cichlid Association. Members could describe in semi-quantitative terms – we would use Likert scale type of survey questions – the dominance and territorial behavior of their species. We could then survey cichlid hobbyists, who spend a lot of time looking at these behaviors in their aquaria, to learn more about diversity and variability of these social dominant systems across species.
Only a limited numbers of species have been studied in nature (in the field) and that’s just going to remain limited for all kinds of reasons. So many more species are available to be looked at and observed in a detailed way in the aquarium.
Also, I have a new graduate student beginning this month who’s very interested in getting involved in public engagement in this way. This is one thing that she might want to become engaged in. So I think there’s a lot that hobbyists can contribute.
The tricky thing is that we lack two things at this point. We lack the training that we need for our students and postdocs (and many of my faculty colleagues) so that they can really communicate in a way with nonscientists that would make that compelling. Then do so in a way where the nonscientists would want to contribute and not just feel like they’re being used for something or being talked down to.
The other thing that is lacking is an infrastructure to actually do this, to bring people together in some way, not just physically but also virtually. The technology is certainly there to collect that kind of information in a way that it can be analyzed in a meaningful and scientifically rigorous way with the appropriate metadata and so on. So we’ve certainly thought about this, but I also acknowledge that these limitations are there at this point.