ONTOGENETIC VARIATION AND THE PLASTICITY OF NEUROBIOLOGICAL AND BEHAVIORAL PHENOTYPES IN THE SOCIALLY MONOGAMOUS PRAIRIE VOLE (MICROTUS OCHROGASTER) A Dissertation Presented to the Faculty of the Graduate School of Cornell University In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by Lisa Christine Hiura August 2020 © 2020 Lisa Christine Hiura ONTOGENETIC VARIATION AND THE PLASTICITY OF NEUROBIOLOGICAL AND BEHAVIORAL PHENOTYPES IN THE SOCIALLY MONOGAMOUS PRAIRIE VOLE (MICROTUS OCHROGASTER) Lisa Christine Hiura, Ph. D. Cornell University 2020 With everchanging environmental contexts and dynamic social partners, the ability to continuously integrate information and make adaptations is essential for an animal’s survival and fitness. Early experiences powerfully shape the phenotypic trajectories of offspring, such that conspecifics can exhibit wildly divergent behaviors in the same contexts. The causes and consequences of social behavioral diversity are rooted in the plasticity of neuroendocrine signaling systems, which also serve fundamental roles in the functional and structural development of the brain. Critically, we still know little of the mechanisms by which complex experiences are encoded in the brains of developing offspring to pattern behavioral variation in latter stages of life. This thesis investigates the impact(s) of multifactorial early life experiences on the ontogeny of neural phenotypes in the biparental prairie vole system. In chapter 2, I describe the ages at which distinct subregions of the medial extended amygdala begin to functionally respond to changes in social context. In chapters 3 and 4 I follow with a characterization of how multiple dimensions of the rearing environment independently and synergistically shape the profiles of oxytocin and vasopressin receptors, their peptide-producing cell groups, and age-specific offspring behaviors. The data reveal that region-specific receptor densities are contingent upon an animal’s sex, a father’s presence or absence within the natal nest, the complexity of the juvenile weaning environment, and the higher-order interactions thereof. Furthermore, the absence of a father during the rearing period predicts a more socially permissive offspring phenotype, and lower numbers of oxytocinergic cells in the adult hypothalamus. However, these outcomes are contingent upon family handling conditions, indicating that alternate early life factors can offset or exacerbate the influence of paternal care. Finally, in chapter 5 I describe the reciprocal effect of variation in pup rearing experiences on parental phenotypes. Parental behaviors are surprisingly consistent across parenting contexts, but the associations between behavior and vasopressin cell groups display experience dependent plasticity. Altogether this body of work exhibits the extensive plasticity of behavior and underlying nonapeptide mechanisms, emphasizing the importance of examining environmental interactions within and across the lifespan of the prairie vole. BIOGRAPHICAL SKETCH Lisa Christine Hiura was born in Hamamatsu, Japan, and moved to the United States at four years old. She grew up in Eugene, Oregon, where she spent much of her time exploring the evergreen forest trails of the Pacific Northwest and trying to get as close as possible to every animal that came across her path. She graduated from North Eugene High School after completing an International Baccalaureate independent research project on racism and stereotypic depictions of marginalized characters in children’s media. Wanting to understand why people do the things that they do, she became engrossed in the study of behavior and pursued her Bachelor of Arts in Psychology at Reed College in Portland, Oregon. At Reed, she began her research career in comparative cognition and behavioral neuroscience and conducted her senior thesis on the reinforcement value of social contact in the laboratory rat. She became deeply interested in the study of social behavior, in particular the neurobiological mechanisms that give rise to individual and species differences in social phenotypes. This interest led her to pursue her PhD in Psychology with a focus on Behavioral and Evolutionary Neuroscience in the laboratory of Dr. Alexander Ophir at Cornell University. There, she began working with the socially monogamous prairie vole, sealing her lifelong obsession with rodents. Funded by a National Science Foundation Graduate Research Fellowship, she investigated the role of early social experiences on social behavioral and neurobiological development, with a focus on plasticity of the neuropeptides oxytocin and vasopressin. v To my mother, whose support is unconditional and fierce And to my husband, the epitome of joy. vi ACKNOWLEDGMENTS I owe everything that I have to my community. There are so many people that deserve recognition for the ways, big and small, in which they have helped me. First and foremost I need to thank my mother, Kazumi Hiura, who is the hardest working person that I have ever had the honor of knowing. She is a veritable fountain of love and support and has spent her life setting an example of resilience for myself and for others. I am where I stand today because of her bravery. I am profoundly lucky to have the privilege of calling her my mother. I am all the more so to get to call her my friend. I have so much gratitude for my whole family in Japan, who beyond a literal ocean and language barriers, have been a source of love and laughter. I would like to thank my lab mates, my compatriots, past and present. Marissa Rice, Caitlyn Finton, Santiago Forero, Angela Freeman, Wen-Yi Wu, Lindsay Sailer, Jesus Madrid, Eileen Chun, George Prounis, Danielle Lee. They have each brought so much joy to my day to day life and inspired me in ways that have influenced my work and my spirit. There is no doubt in my mind that each will continue to do so for the other fortunate friends in their lives. I am eternally grateful for my research assistants for their endless enthusiasm and dedication. They came into the lab to learn about science but were the ones to teach me what it truly means to be a scientist. Practicing mentorship has been among the most fulfilling components of my graduate training. It has been an honor to work with each and every one of the students that have joined my projects. I would especially like to thank Vanessa Lazaro and Mandy Chan for their devotion to the vii voles, their brilliance in their work, and their patience with me. Aubrey Kelly has done more for my personal and professional development than most people I have met in my lifetime. She has been a fierce advocate, a steadfast friend, and an inspirational mentor. She taught me about the perfect pairings between wine and food, tissue and antibody. I race behind her in the trail that she has blazed for myself and for other women in science. My committee members, Elizabeth Adkins-Regan, Katie Kinzler and Mike Goldstein, have been constant sources of intellectual stimulation and wisdom. My conversations with them have radically changed my perspectives on biology and psychology, and these teachings have forever altered my developmental trajectory. I profusely thank Alex Ophir for taking a chance on me. For pushing me and teaching me and believing in my capacity to succeed. Even when he ceases to be my formal advisor, he will be a lifelong mentor to myself and my colleagues. I have changed more under his tutelage than that of any other mentor that I have ever had. I could write an entire separate dissertation about the love of my life, Alan Baur. He followed me across the country with 100% confidence in our path, even when I was unsure of my own plans. He’s been a daily source of encouragement, both to keep pushing and to rest. This feat is as much his as it is my own. I aspire to be even a fraction as diligent and creative and fearless and kind as he demonstrates himself to be every day. He has changed my life in innumerable ways, and I wake up every single day excited to see what our next adventure entails. I won the lottery when I joined the Marshall / Baur family. Sue and Rob have treated me as one of their own long before the wedding. Kelly, Will, and Ali have viii shared their love and kindness and inventiveness with me, and have become the family that I never knew that I could have. Wesley and Sienna are the most delightful niblings whom I have the honor of watching grow, even if from afar. My community of friends, too many wonderful people to name here. Just a few of my board game buddies and fiction co-enthusiasts - Kristina Smiley, Sam Carouso- Peck, Katerina Faust, Mary Elson, Erin Isbelin, Joel Tripp, Hannah Chapman Tripp, Raj Anderson. My trivia team, for making 4th place always feel like 1st, and for teaching me to double down. My kickball team, Ballz to the Falls, for reminding me that even when you’re not the best, you can certainly have the most fun. For those times when I had to force myself to think about something other than rodents, I leaned on these friends. Venting and dancing and laughing with them feels like coming home. I would be remiss if I were to ignore my beloved cat, Henry, who brings me endless laughter and amusement. At both of our expenses. And of course, godmother to our cat, Phoebe Young, for being our first and forever Ithaca friend. The faculty of the Psychology department and the BEN program have taught me innumerable lessons, academic and beyond. The staff have made this work possible. Without Pam Cunningham, Cindy Durbin, and Lisa Proper, my experience in the program would have been much less joyful. I will miss walking the halls and seeing all of their faces and hearing their lively discussions. The CARE staff deserve so much recognition for their daily contributions to our work.