Alexander Ophir:
(Wednesday, June 27, 11am)
Perhaps no neuromodulatory system is more important for social behavior than nonapeptides (oxytocin and vasopressin) and no behavior is more complex than reproductive strategy. I will discuss how early experience shapes reproductive decisions in prairie voles. The motivation toward monogamy or polygamy, with memory modulated by nonapeptides, depends on early experience and individual ability to assess the social and spatial landscape.
Ophir AG (2017) Navigating monogamy: Nonapeptide sensitivity in a memory neural circuit may shape social behavior and mating decisions. Frontiers in Neuroscience. 11, 397. doi: 10.3389/fnins.2017.00397
Prounis GS, Foley L, Rehman A, Ophir AG (2015) Perinatal and juvenile social environments interact to shape cognitive behavior and neural phenotype in prairie voles. Proceedings of the Royal Society B. 282, 1819, DOI: 10.1098/rspb.2015.2236
Ophir AG, Wolff JO, Phelps SM (2008) Variation in neural V1aR predicts sexual fidelity and space use among prairie voles in semi-natural settings. Proceedings of the National Academy of Sciences, USA. 105, 1249-1254. [PMID: 18212120]
Bartz, J. A., Zaki, J., Bolger, N., & Ochsner, K. N. (2011). Social effects of oxytocin in humans: context and person matter. Trends in Cognitive Sciences, 15(7), 301-309
Algoe, S. B., Kurtz, L. E., & Grewen, K. (2017). Oxytocin and Social Bonds: The Role of Oxytocin in Perceptions of Romantic Partners’ Bonding Behavior. Psychological science, 28(12), 1763-1772
Maybe to add to my question about euthanasia, the voles tails are also clipped to permit genotyping and identification.
ReplyDeleteMy question is: why the need of tail clipping if individuals are already marked with eartags to allow identification? And since the specimens are euthanised, couldn't their corpse be used for genotyping, rendering thus useless the clipping of their tails?
I am specifically referring to the paper ''Social but not genetic monogamy is associated with greater breeding
Deletesuccess in prairie voles'' which is not listed amongst the other references of this page.
I also had a question about euthanasia (and maybe someone on the blog can help me); is there comities that regulate studies in the USA? M. Ophir said that he thinks the advantages are greater and can explain the need to euthanize, but it seems subjective (he didn’t explain much more). Is there some panel that review studies propositions in USA before they can proceed?
DeleteThere are two elements to these questions. The first question was about our method and why collected tail clips before euthanasia if we could have taken the samples after the animals were sacrificed, presumably avoiding the need to collect the tail clip sample and avoid any associated pain or distress. The reason for this is that there was no guarantee that we would recover all animals after the experiment was completed. If we did not recover an animal, we would not be able to know which animals were the parents for the offspring and this was a very important thing for us to determine for the aims of the experiment. Taking a small tissue sample from which we could collect DNA before the animals were introduced into the field enclosures enabled us to ensure we could test all males for paternity afterward. In other words, if we didn't recover the male, we still had a DNA sample.
DeleteThe second question is much larger about animal ethics and regulation (specifically within the USA). The answer to this is there are many regulating institutions within the US (as there are within Europe, Canada, and many other countries). The regulations across countries are not always 100% concordant, but there is a tremendous amount of agreement across these agencies. The National Research Council of the USA have published Guidelines on the ethical treatment of animals in scientific research for decades (often updating the guidelines to improve the standards and stay current). Most research institutions (and all major research institutions) in the USA have a committee (the Institutional Animal Care and Use Committee, IACUC) that reviews the animal welfare, ethics, pain/distress, and all other aspects of these kinds of questions for every experiment conducted at the research institution. They us a combination of the NRC regulations and other resources on animal ethics to ensure that work is justified and potentially valuable, that if the animals involved in the research will experience any potential pain or distress, that it will be minimized as much as possible, and that all efforts to reduce the number of animals, or ideally answer the scientific questions with any other possible alternatives. For a more exhaustive review of considerations that are evaluated, the kinds of government regulations that exist, and other related information, refer the the guideline published by the Animal Behaviour Journal: https://www.sciencedirect.com/science/article/pii/S0003347216303517
Delete(Apparently "Unknown" is Alexander Ophir's blogger login.)
DeleteIf you are still reading this. Sorry that I'm so late!
DeleteYou said:
"The reason for this is that there was no guarantee that we would recover all animals after the experiment was completed. If we did not recover an animal, we would not be able to know which animals were the parents for the offspring"
You also said (in a later reply to Jeremy Buist):
"it is illegal (and unethical) to raise animals in the lab and release them into nature"
My main question: Does "not recovering an animal" and therefore being "unable to euthanize it" imply "having lost it in nature" (which is illegal)...?
My backup question: Supposing those field animals do not count as lab animals, do they still need to be euthanized and why (I suspect they count as lab animals, which would validate my previous question)?
I see some kind of contradiction here, so quite likely there is something I'm missing. I would also appreciate if you could clarify what is meant by "unrecoverable animal".
Thank you!
I asked you after your presentation if it could be a good idea to consider the baseline level of norepinephrine between residents and wanderers males to understand the way they manage de trade off between exploitation and exploration, which they are facing when they choose to focus their attention on one or many female... That being said, I didn't understood wich upstream level hormone you where actually investigating in your research. Could you brief me about that or give me some references?
ReplyDeleteWe primarily measure nonapeptides (oxytocin & vasopressin). We know from work in mammals (like voles), birds (like finches), frogs, fish, and other taxa that these hormones are directly important in various forms of social behavior, memory, and other physiological responses. I recommend reading the following review article:
Deletehttps://dx.doi.org/10.1016%2FS0079-6123(08)00401-9
During the presentation, you said that there are two different types of brain between paired/residents and single/wanderers : that the nucleus accumbens was not correlated with the other structures in the single/wanderers one. That made me think if there are any "plasticity" available in the voles brains. If we compare, in human, sometimes some circuits are not well developped but if we are put in the good environment and conditions, we can develop those circuits. Therefore, is the same mechanism possible for the voles brain? Could we manage, hypothetically, the environment to "help" the circuits of the brain - between the nucleus accumbens and other structures - of wanderers to develop and then become more like the residents?
ReplyDeleteIn short - yes. These are exactly some of the questions we are studying. We focus on how social context impacts neural plasticity, although we focus on plasticity at the gene expression level (hormones/receptors, etc) not the at the neuronal circuit level (e.g., neuron connections, etc). Understanding the epigenetic mechanisms that underly this plasticity is one example of a way in which we might be able to understand how the environment can directly impact plasticity in neural function. I'd go as far as to say that at a broad level, these same mechanisms are operating more or less in the same way in all animals. But I would also say that the outcomes of these same mechanisms might respond to the environment differently and express themselves differently in different animals and contexts.
DeleteHi, I enjoyed your presentation,
ReplyDeletebut I wasn´t really convinced by your argument attempting to justify the euthanasia of the voles. Which animals wouldn´t you euthanize for some scientific benefit? To what extent does the end justify the mean here? Additionally, what specific benefits, besides the general increase of scientific knowledge about brains, will this research have for prairie voles?
Also (unrelated), what environmental conditions was the "working" lab set-up meant to replicate, and how did you eliminate the possibility that there was something peculiar about the lab setup other than the intended features that could have influenced the outcome?
Thanks!
Your second question is much easier to address so I’ll start there. Our ‘working’ condition was intended to take a small step closer to the kinds of trade-offs that animals must make when raising their offspring. It is purely artificial to raise animals in a context where they have all the resources they could ever need within inches of their nest and acquiring them requires no effort. By asking the animals to walk 5 feet to eat, we set up a scenario in which animals had to put just a little bit of effort into ‘foraging’ (I use the term foraging loosely here). The ‘working’ condition required animals to traverse a slight angle/grade. All animals were able to accomplish this with no obvious detrimental effects. (The hills you have to walk in Montreal require more effort to climb than this angle did, to give some perspective). We closely monitored food consumption and weight and food consumption was stable and weight differences between conditions were not seen. So the animals had to make some ‘choices’ do I eat OR do I brood my offspring. We set up many control conditions to ensure that the experimental design wasn’t the cause of our results.
DeleteThe nature of your first question/comment is very important and very deep. Based on the one question raised during my Q&A and some of the questions posted on this blog elsewhere, I realize that this is a question that students of this summer school are very interested by. Sadly, a back-and-forth over a blog is an incredibly poor place to have the thoughtful conversation that your question deserves and to cover the nuance that your question requires. If my comments were not terribly compelling during my Q&A, then I surely did not adequately articulate the importance of some of the many reasons why animal research is important or how my work fits into that framework. There are many people much smarter than I am that can provide you with good arguments, and I imagine there are many people that have counter arguments to these people. I would like to make clear, I am not here to universally defend all animal work of any kind, carte blanche. I’ll do my best to discuss some thoughts here that guide my perspective on the important role that animals have in scientific discovery, some of the things that guide my views, and a few of the things that I think make the work I do justifiable and valuable. But I caution that I simply can’t capture everything there is to say about this in a simple posting.
DeleteSome people eat meat without thought, some people eat meat but take precautions to ensure the animals they consume were treated well, some do not eat meat, some do not eat or use any animal products, and some people believe that no one should use/consume animal products for any reason. Notably, people within each of these categories on this non-exhaustive list also disagree with each other on some details. My point is that people vary in what they value and the rules that govern their values. The use of animals in research is similar but I would say with confidence that the variance is dramatically reduced among the scientific community. Moreover, animal ethics is taken very seriously and is highly regulated (see the comment left above regarding this) to ensure that even if some rogue people don’t value ethics in animal research, they still adhere to very high standards. Every scientist that works with animals must consider if the kind of work they conduct is worth it and ultimately must be comfortable with what they do. They should give serious consideration to how the work that they do affects the animals they work with, and what the greater good of their work ultimately is.
DeleteWhether you are motivated by improving human mental health and well-being, improving our understanding of basic brain function to discover basic principles of behavioral biology, or are interested in identifying the basic roots of what makes humans unique (and identical) to other animals, I think there are plenty of good reasons to justify the use of animals in research. The work on prairie vole development that I conduct aims to reveal genetic, epigenetic, and neural mechanisms that govern social behavior, identify pathways for which behavior can develop (with an eye toward understanding the development of dysfunctional behavior), and provide new insights into building a framework upon which developing medical treatments to improve human mental health and well-being could be built. The work I do to understand reproductive decision-making has a larger aim to understand the ecological and social contexts that modulate behavior and the brain function that underlies this. I personally believe this work and these goals have great value for human society and even non-human well-being.
DeleteOn balance, the nature of the work I conduct is primarily non-invasive and mostly based in behavioral observation and alteration of social environment. Some of the work we conduct requires brief (usually extremely brief) and very minor discomfort (and when we do this, we go to great lengths to take precautions to minimize discomfort as much as possible). Some of our work requires euthanasia. It is illegal (and unethical) to raise animals in the lab and release them into nature. As a result, we only use the minimum number of animals necessary for accomplishing the scientific goals we outline. Several independent panels of scientific minds must agree that the work we want to conduct is justified and has merit. This review occurs before the experiments are run and after the work is complete. Similarly, both before and after the work has been initiated, several panels of ethics reviewers must concur with the justification of the use of our animals, and the treatment of the animals during the process. In other words, it is not just me that must be convinced that the work is worthwhile and that I am ensuring that the animals are being treated with the best possible intentions.
You asked which animals I wouldn’t euthanize for some scientific benefit and if the ends justify the means. What I will say here is that there are a number of species I don’t personally feel comfortable using in science (regardless of whether pain/distress and/or euthanasia are involved). I will also say that I think there are many scientific experiments that I could imagine that I do not believe justify the use of animals. I don’t conduct that kind of work and I don’t work with the animals that I don’t feel comfortable working with. But this question is not so simple and ultimately the question, the appropriateness of the animal used to address the question, and the overarching benefits are factors that have to be evaluated together. I believe that there is an enormous value to improving and expanding human knowledge about brain and behavior. This can have a major impact on quality of life for human and non-human animals. I think that your question comes down to what societal, cultural, and personal values and ideals are shared by most people, and I hope and believe that most people would agree that the work that I conduct is valuable. But I certainly don’t have all the answers on this difficult question.
Ophir’s presentation illustrated how the environment impacts behavior. I was surprise to see how father’s presence or absence can influence social approach of voles in their adult life. We sure can make associations with humans’ social behavior and it is encouraging to see that socialization later in life can reduce the effects of an absent father. About the difference of sex, it would have been interesting to know how the females behave. For example, how does the social male environment influence their spatial learning? And how do behave female wanderers? Maybe the observation of females can explain some behavior of the males.
ReplyDeleteI agree completely that the story is incomplete without considering what females are doing. We have done a little work on this, but need to do more (and I'm hoping to convince some of my students to pursue questions about the female decision-making much more). We have one or two papers that focus on females, and a few more unpublished studies that we are working toward finishing. I will point out that our developmental work has shown that males nonapeptide phenotypes are potentially more plastic and sensitive to developmental perturbations. I think this is why we (and others) tend to see male voles impacted by early life social experience more than females. This feeds into the focus on males. However the flip side of this is to wonder why females are so robust and what makes them that way - this is a very interesting question that we are pursuing. Understanding the sex differences in wandering / residency is very important and I think the factors that shape male tactics are similar but also very different than those that impact females. This paper might speak to some of the questions you are asking:
Deletehttps://www.sciencedirect.com/science/article/pii/S016643281300106X
This presentation showed how voles reproductive strategies are shaped by the way they adapt to their environment. Lots of focus was put on male behaviors and it felt like more assumptions rather than observations were made on how females behave. During the presentation, the reproductive strategies of the male voles often seemed generalized to the reproductive strategies of other male mammals as well as humans. It seemed like a sociobiological stretch. It would've been interesting and valuable to include some studies on homosexual and bisexual behaviors among mammals to show how these specific social and sexual interactions also help shape monogamous relationships and reproductive strategies. Linking a great article on the matter by R.C. Kirkpatrick: http://courses.washington.edu/evpsych/Kirkpatrick%20on%20homosexuality%20(short)%20-%20CurrAnthro00.pdf
ReplyDeleteSo in part, please see the comment immediately above. We have a more complete understanding of the male story which is why I focused the talk on this, but we do know somethings about the females too. To my knowledge, prairie voles do not engage in homosexual behavior of any kind. Annaliese Beery (https://www.smith.edu/academics/faculty/annaliese-beery) has studied same sex social affiliation (not the same as homo-sexual behavior) in meadow voles and found some very interesting things about bonding and affiliation that you might find interesting. I am worried I didn't explain the difference between social relationships and sexual relationships well enough in my talk, but these are very different and easily conflated ideas. Both are important for shaping mating decisions, but they are also quite different factors. And to be clear, there may be a few principles that in a very general sense apply to voles, humans and other mammals, but 1) a vole and a human are very different and at best share some similar traits that may or may not have evolved the same ways for the same reasons, and 2) monogamy of any form is quite rare in mammals so what you see in voles and humans is not likely to be the most common pattern seen in other mammals. I did not mean to over generalize our results.
DeleteL’environnement social dans lequel un individu naît et grandit, à différents moments, peut altérer d’un manière considérable le développement. Alexander Ophir et son équipe ont regarder cela en prenant comme sujet les campagnoles des champs, qui ont tendance à être monogame et à former des couples. Ainsi, on a pu remarquer une différence dans l’environnement social qui menait certains campagnoles mâles ou femelles à être des vagabonds (wandering) ou des “résidents”. L’équipe d’Ophir a regarder l’effet des soins paternels sur les petits. En effet, l’absence paternelle semble affecter le développement et la formation de couple. De manière intéressante, s’ils se retrouvaient plus tard dans un environnement social riche d’interactions, ces campagnoles semblaient revenir à une vie sociale plus normale, tandis que ceux se trouvant dans un environnement social moins riche semblaient s’isoler. Conséquemment, l’environnement en général et les interactions sociales qui y ont lieu à différents moments du développement sont d’une importance manifeste dans le développement cognitif d’un individu et pour ce qu’il deviendra plus tard, non seulement chez les humains mais aussi chez les animaux.
ReplyDeleteJe suis tout à fait d'accord avec vous. Tout comme chez l'humain, les interactions sociales et les expériences consolidées chez les jeunes individus vont, d'une manière ou d'une autre, influencer le développement et la façon de raisonner de l'individu, que ce soit au niveau cognitif, affectif ou social. Ainsi, Mr. Ophir aborde l'écologie cognitive en questionnant le processus d'accouplement chez les individus en analysant le mécanisme d'acquisition, de rétention et d'usage de l'information et comment cette évolution influence la neuro-écologie de ces individus, soit la façon dont leur cerveau s'adapte et varie en fonction cognitive, par rapport à leurs besoins et demandes de leurs environnements.
DeleteJe vois que M. Ophir a répondu ci-haut en partie à ce qui aurait été ma question, à savoir si les résultats de cette étude sur les campagnols sont généralisables à d'autres espèces dont notamment l'espèce humaine (je cite): "And to be clear, there may be a few principles that in a very general sense apply to voles, humans and other mammals, but 1) a vole and a human are very different and at best share some similar traits that may or may not have evolved the same ways for the same reasons, and 2) monogamy of any form is quite rare in mammals so what you see in voles and humans is not likely to be the most common pattern seen in other mammals. I did not mean to over generalize our results." Dans cette perspective, je ne peux que partager les préoccupations émises ci-haut par certains de mes collègues étudiants quant à la nécessité d'euthanasier les sujets pour compléter les données. N'aurait-il pas été possible d'observer les cerveaux autrement ou de mesurer la présence et les taux des agents biochimiques par prélèvement? Le mode de vie et les particularités (ex. potentiel monogame)des campagnols des prairies sont hautement intéressants, mais il me semble que le rapport coût/bénéfice de l'expérience pour le bien-être et le conservation de cette espèce, puisque les résultats seraient peu généralisables, m'apparaît en l'espèce très élevé...
ReplyDeleteIndeed, the social environment plays a considerable role in cognitive development and in the acquisition of social skills. M. Ophir introduces the monogamy among the voles and I would like to know if during the disappearance of a male in a couple of voles, another male comes to try to replace it and if this paternal substitution plays a beneficial role for the little ones?
ReplyDeleteThank you.
We have not observed this behavior, but I suspect that this does happen (new males forming a pair with a female that lost a mate to defection (leaving the pair) or death (e.g., predation). I don't know if the new male would take part in rearing the young of a previous male in nature. In the lab, males will perform alloparental care (take care of offspring that are not theirs), and we have seen interesting effects of alloparental care on social behavior of pups as adults. But they also engage in infanticide, and in other rodents infanticide is the most common behavior when pups from another male are present at the nest. But I think it's a very interesting question.
DeleteC'est vraiment intéressant de voir comment l'evironnement peut modifier le comportement de ces petits animaux. Aussi, j'ai trouvé vraiment impressionnant la complexité avec laquelle ils développement leurs liens, leur façon de se nourrir ainsi que l'impact des liens parentaux/présences parentales sur les bébés. J'ai trouvé que les questions sur l'euthanasie apportaient un point de vue important sur les études scientifiques. Tout au long de l'école d'été cette question est revenue souvent et il est difficile de décider dans quelles circonstances les études scientifiques prônent sur le bien-être des animaux et quand est-ce l'inverse.
ReplyDeleteYou mention that males are physically “wired” to be monogamous because, appart from the nucleus accumbens, there are no differences in structures involving oxytocin and vasopressin receptors. You also mentioned that those two hormones where sufficient to predict reproductive strategies. However, according to Aragona et al. (2006), there is quite a big differences in dopamine receptors in the two types of behavior. D1 receptors are more abundant in wanderers, while D2 receptors are more numerous in residents. In your studies, did you have the chance to look at the additive and interactive effect of those three neurotransmitters and neuropeptides on reproductive behaviors?
ReplyDeleteAragona, B. J., Liu, Y., Yu, Y. J., Curtis, J. T., Detwiler, J. M., Insel, T. R., & Wang, Z. (2006). Nucleus accumbens dopamine differentially mediates the formation and maintenance of monogamous pair bonds. Nature neuroscience, 9(1), 133.
Aragona did not compare residents to wanderers. His work demonstrated that different concentrations of the dopamine receptors in different parts of the NAc functioned to either facilitate bond formation or facilitate bond maintenance. The former case works with the system that I discussed. The latter works in a different way to shift the weights of social valence to alter behavior. We have done a little work with dopamine, but not much. I think it's crucial to the larger system. I did not mean to imply that only OT and VP are responsible for monogamy or the other things I discussed. But I do think that the OT/VP system in the 'bonding circuit' predisposes males to form bonds. Whether that impact maintenance or not, I don't know, but I suspect it doesn't.
DeleteAs any studies been made where the males would be restricted inside a particular territory and that the female would have to select and go to the male of their choosing?
ReplyDeleteThis could be done using RF chip/collars on animal allowing only passage through a “gate” between territory to only allow free roaming for the females.
Not in the filed context (which is something that I think would be fantastic, but challenging). This has been done under lab conditions, and could probably use a little more work than has been done to date.
DeleteSince vasopressin and the oxytocin receptor are found throughout the body, does this mean that these norapeptides when released in the central nervous system during bonding also have global effect?
ReplyDeleteOT and VP have several sources in the brain that only target other brain regions. They also have other sources in the brain that enable release into the blood stream and act on peripheral organs (i.e., non-brain sites of action). For example in the Paraventricular nucleus of the hypothalamus (PVN) there are some cells that are specialized to target other parts of the brain and other cells that are specialized to release OT and VP to the blood. Some of the sources of release are coordinated (i.e., when OT is released and acts on brain targets, it is also released to the periphery and could target other body organs), but sometimes the release is not coordinated.
DeleteL'influence du gène Avpr1 me porte à réfléchir sur la génétique. Puisqu'on peut relier la présence de certains gène avec certains comportements, je comprends l'importance d'en idenfier la présence dans une étude sur l'esprit des autres espèces. Est-on témoin de l'évolution de l'influence d'un gène dans la phylogénie? Cette évolution tend-t-elle à suivre certaines lois? Tendre vers le développement de comportements sociaux par exemple? Y a-t-il d'autres espèces qui portent elle aussi ou pas le gène Avpr1. L'humain par exemple? Pourquoi ce gène influence-t-il aurant le mode de vie des campagnoles en particulier et pas des autres espèces (ou l'influence-t-elle?)
ReplyDelete