Implications of oxytocin in speech

Abstract

[eng] In my thesis I investigate the evolution of human sociality and its possible role for providing a scaffold to the evolution of language. My approach is multidisciplinary and includes studies ranging from genomic analyses to behavioral experiments in songbirds. My hypothesis is that oxytocin is a good candidate molecule that could help us decipher the role the evolution of our sociality plays in the evolution of language, as well as the role of social reward/motivation in language acquisition. I study the evolution of human sociality mainly through the lens of the ‘self-domestication’ hypothesis, according to which natural selection in humans favored increased prosociality over aggression (Hare 2017), giving rise to a behavioral and an anatomical phenotype that is reminiscent of the one we witness in domesticated species. In Theofanopoulou et al. 2017 (Chapter 1) we examine if this old hypothesis, stemming from thoughts formulated in Darwin 1888, makes sense at a genetic level. We identify a statistically significant intersection of genes under positive selection in modern humans and in one or more domesticated species. Oxytocin/vasopressin receptors are among the genes that have been studied the most in the context of domestication and social cognition. We studied variant changes in these genes between modern humans and our extinct (Neanderthals and Denisovans) and extant relatives (macaques, bonobos, chimpanzees) (Theofanopoulou et al. 2018, Appendix Chapter 1) and report 29 variants which were clustered based on their presence in the species studied and discuss their functional relevance. In Theofanopoulou 2016 (Chapter 2) I put together studies from the literature that point to a role of oxytocin in modulating the multimodality that characterizes our linguistic ability. I follow a bottom up approach, starting off from possible genetic interactions that could support this role, and ending with evidence from EEG (electroencephalography) and behavioral studies. In Theofanopoulou, Boeckx, and Jarvis 2017 (Chapter 3), we propose specific neural mechanisms through which oxytocin could modulate brain regions that are specialized for vocal/speech learning directly, or indirectly through its interaction with dopaminergic neurons. In Theofanopoulou et al. (Appendix Chapter 2) we experimentally address the traditional idea that social reward enhances learning in the realm of vocal learning. In human studies it is not possible to dissociate social reward from vocal learning and study its exact impact on it, so we attempted such a dissociation developing a vocal learning behavioral paradigm with and without social reward in zebra finches. We found that social reward gates their vocal (pitch) learning. In Theofanopoulou et al. (Appendix Chapter 3), we manipulated the oxytocin-system in zebra finches and found that an administration of an oxytocin-antagonist leads to a significant drop in the number of introductory notes in their love song. In Theofanopoulou et al. (Appendix Chapter 4) we study the synteny (genomic territory) of the oxytocin and vasopressin/vasotocin ligands and receptors in 33 vertebrate genomes and 4 invertebrate outgroups and we propose an evolutionary history and a new universal vertebrate nomenclature for all these genes. In conclusion, Ι believe that this thesis offers a fertile ground for future experiments seeking to unravel the effect of social reward in vocal learning developmentally, something that can shed light to the effect that the evolution of our sociality might have had in the evolution of a fully- fledged language in our species. My thesis also lends evidence to a specific hypothesis under which our sociality can be studied, the ‘self-domestication’ hypothesis. Further, the oxytocin

and vasotocin systems are shown to be good candidates for uncovering changes that might have had an effect on the evolution of prosociality, but also changes that affect vocal learning behaviors. Lastly, my thesis proposes a universal nomenclature for the vertebrate oxytocin and vasotocin ligands and receptors that is meant to allow easier translation of findings across vertebrates and to foster more informative design of functional experiments across species. References Darwin, C. (1888). The descent of man and selection in relation to sex. Murray. Hare, B. (2017). Survival of the Friendliest: Homo sapiens Evolved via Selection for Prosociality. Annual Review of Psychology, 68(1), 155–186. https://doi.org/10.1146/annurev-psych-010416-044201 Theofanopoulou, C., Andirko, A., & Boeckx, C. (2018). Oxytocin and Vasopressin Receptor variants as a window onto the evolution of human prosociality. BioRxiv, 460584. doi: http://dx.doi.org/10.1101/460584. (Appendix Chapter1) Theofanopoulou, C. (2016). Implications of oxytocin in human linguistic cognition: From genome to phenome. Frontiers in Neuroscience, 10(271). https://doi.org/10.3389/fnins.2016.00271 (Chapter 2) Theofanopoulou, C., Boeckx, C., & Jarvis, E. D. (2017). A hypothesis on a role of oxytocin in the social mechanisms of speech and vocal learning. Proceedings of the Royal Society B: Biological Sciences, 284(1861), 20170988. https://doi.org/10.1098/rspb.2017.0988 (Chapter 3) Theofanopoulou, C., Gastaldon, S., O’Rourke, T., Samuels, B. D., Tiago Martins, P., Delogu, F., … Boeckx, C. (2017). Self-domestication in homo sapiens: Insights from comparative genomics. PLoS ONE 12(10): e0185306. https://doi.org/10.1371/journal.pone.0185306 (Chapter 1) Theofanopoulou, C., Lipkind, D., Tchernichovski, O., Boeckx, C., & Jarvis, E.D. (Appendix Chapter 2). Selective vocal learning in a social reward context. Theofanopoulou, C., Boeckx, C., & Jarvis, E. D. (Appendix Chapter 3). Pilot study: testing the effect of intranasal administration of an oxytocin-receptor antagonist in adult zebra finch directed singing. Theofanopoulou, C., Gedman, G., Cahill, J. A., Boeckx, C., & Jarvis, E.D. (Appendix Chapter 4). A proposed universal nomenclature for the oxytocin and vasotocin ligand and receptor families and their evolutionary history.