The overarching goal of the proposed research is to characterize the effects of early family structure on behavior, expression of genes encoding nonapeptides and their receptors, and epigenetic modifications of these genes. The nonapeptides vasopressin (VP) and oxytocin (OT) are important modulators of behavior, including aggression, anxiety, social behavior, and parental care. Early life experiences are known to alter behavior and gene expression by genomic and epigenomic means, and may also alter the function and anatomy of VP and OT circuitries. Most of what is known about the relationship between early life experience and the neural and genetic mechanisms regulating adult social behavior comes from uni-parental species. To understand the significant factors that may shape human health, one must consider the influence of fathers on offspring and mothers. This can be achieved by using a bi-parental model, such as the socially monogamous and bi-parental prairie vole (Microtus ochrogaster). Few studies have examined the impact of paternal influence on offspring development or the extent to which paternal care influences the development and epigenetic modification of nonapeptide systems. The central hypothesis of this proposal is that paternal deprivation for offspring and loss of a co-parent for mothers will induce social deficits, increase anxiety and aggression, and alter the nonapeptide systems regulating these behaviors. To address this hypothesis, Aim 1 examines behavior, nonapeptide and receptor gene expression, and epigenetic modifications of these genes from prairie vole offspring raised by a mother and father, a mother and """"""""poor"""""""" father, or only a mother. Variation in paternal quality will be induced by administering antisense oligonucleotides targeting vasopressin 1a receptors in the lateral septum, where VP is known to promote paternal care. Using the same experimental breeding group design in Aim 1, Aim 2 investigates the plasticity of epigenetic modifications to nonapeptide genes by observing DNA methylation in offspring at various points throughout development. Finally, in Aim 3 the behavioral, neuroendocrine, and epigenetic impacts of having a co-parent on the mothers serving in Aim 1 will be examined.
Aim 1 will reveal the relative impact of paternal deprivation on the development of the brain and behavior in offspring. Most studies of epigenetics characterize the influence of experience at a single point in life;
Aim 2 will be the first effort to examine the plasticity of epigenetic modifications to nonapeptide genes throughout postnatal development.
Aim 3 will represent the first attempt to examine the behavioral and physiological impacts of being a single mother on maternal health in a non-human animal. The results from these studies will create a foundation of basic knowledge about the social and developmental consequences on nonapeptide-mediated mental health disorders characterized by social deficits, anxiety, and aggressive tendencies. The experiments will also serve to develop a non-human model for single-parent families and are designed to improve both mental and physical health in the process of human development.

Public Health Relevance

Understanding the impacts of the early social environment on behavior and the brain can provide insight into the genetic, epigenetic and neuroendocrine mechanisms underlying numerous human behavioral disorders. Our proposed experiments will contribute to translational social neuroscience by identifying potential causes of social dysfunction and isolating critical periods for intervention in children and mothers. These studies lay the groundwork for future advances in the individualized treatment and prevention of a number of behavioral disorders affecting both children and adults, including disorders characterized by social deficits, anxiety, and aggression (e.g., autism-spectrum and anxiety disorders).

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Freund, Lisa S
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Cornell University
Schools of Arts and Sciences
United States
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Hiura, Lisa C; Kelly, Aubrey M; Ophir, Alexander G (2018) Age-specific and context-specific responses of the medial extended amygdala in the developing prairie vole. Dev Neurobiol 78:1231-1245
Kelly, Aubrey M; Saunders, Alexander G; Ophir, Alexander G (2018) Mechanistic substrates of a life history transition in male prairie voles: Developmental plasticity in affiliation and aggression corresponds to nonapeptide neuronal function. Horm Behav 99:14-24
Kelly, Aubrey M; Hiura, Lisa C; Ophir, Alexander G (2018) Rapid nonapeptide synthesis during a critical period of development in the prairie vole: plasticity of the paraventricular nucleus of the hypothalamus. Brain Struct Funct 223:2547-2560
Kelly, Aubrey M; Hiura, Lisa C; Saunders, Alexander G et al. (2017) Oxytocin Neurons Exhibit Extensive Functional Plasticity Due To Offspring Age in Mothers and Fathers. Integr Comp Biol 57:603-618
Kelly, Aubrey M; Ophir, Alexander G (2015) Compared to what: What can we say about nonapeptide function and social behavior without a frame of reference? Curr Opin Behav Sci 6:97-103