Alison M. Bell, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): Despite the obvious costs to individuals and society and importance for health, we know relatively little about the etiology of risk-taking behaviors. Progress toward understanding the genetic and environmental factors influencing the propensity to engage in self-harm, violence and sensation seeking behaviors will be hastened by the availability of a genomically tractable animal model. Our long term goal is to develop stickleback fish (Gasterosteus aculeatus) as a model system to understand how genes interact with the environment to influence behaviors. The overall objective of this application is to identify and test candidate genes and pathways underlying natural variation in risk-taking behaviors. Our central hypothesis is that there are inherited and environmentally-responsive genes that affect risk-taking behaviors in sticklebacks, and those genes are shared with other animals, including humans. The rationale that underlies the proposed research is that an unbiased approach to studying natural variation in the propensity to engage in risk-taking behaviors which are both genetically based and environmentally-sensitive is likely to identify candidate genes that are relevant to human health. Identification of the genes pathways underlying risk-taking behaviors will contribute to the NIH mission to improve the health of the nation by aiding psychopharmacological efforts for the treatment and diagnosis of externalizing disorders in humans. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) Identify genes associated with differences in risk- taking behaviors between individuals and populations; 2) Identify genes underlying risk-taking behaviors that are responsive to adverse environmental conditions; 3) Test candidate genes related to risk-taking behaviors in replicated populations. Under Aim 1, the gene expression profiles of risk-prone versus risk-averse individuals will be compared using whole-genome expression microarrays. Under the second Aim, the behavior and gene expression of individuals that are exposed to stressful environments will be compared against unstressed conspecifics. The two stressors are absence of parental care, which has an important effect on risk-taking behaviors in this species, and exposure to predators during development. Under Aim 3, the genes that are good candidates from Aims 1 and 2 will be tested in independent, replicate populations. This timely project capitalizes on the availability of new genomic information for an organism with a well-described and fascinating behavioral repertoire that until recently has been exempt from molecular dissection. The key innovation of this work is that it takes advantage of genetic and environmental sources of variation to identify candidate genes and uses the unique evolutionary history of sticklebacks to test a biomedically-relevant hypothesis in a replicated manner. The proposed studies use a new animal model to address fundamental questions about the origin of behaviors that have adverse consequences for health. The studies have potential application to understanding the etiology of human psychopathology. The proposed research has relevance to public health, because it will suggest candidate genes and pathways for the diagnosis and treatment of behavioral disorders in humans. [unreadable] [unreadable] [unreadable]

Animal personality, also known as behavioral syndromes and temperament, refers to consistent individual differences in behaviors across time and/or contexts. This field seeks mechanisms that can explain why individuals behave consistently and why they behave differently from each other. Recent models suggest that responsiveness, or how sensitive an individual is to changes in their environment, might be an especially important axis of behavioral variation. While the importance of the social environment on personality traits has long been recognized in human personality research, this factor is only starting to gain attention in animal personality research. The goal of this project is to investigate how repeated social interactions might promote consistent individual differences in responsiveness and other personality traits. The proposed studies will reveal whether social familiarity promotes individual behavioral consistency and whether changes in group composition cause individuals to modify their behavior. These studies will use threespine sticklebacks, a model behavioral organism that demonstrates extensive variation in responsiveness and other personality traits. In the spirit of this grant, collaboration with a local high school has been initiated, where students in the AP biology course will use sticklebacks to learn about environmental influences on behavior. Students will develop, design and execute their own experiments to determine how sticklebacks? behavior changes in the face of environmental stressors; the end result will be poster presentations that the students will give to their peers and teachers. Given the rapid rate of anthropogenic change to the environment, understanding why some individuals are more responsive to environmental change than others has important conservation implications. Moreover, understanding the causes of variation in responsiveness in diverse organisms, including humans, can provide insight into individual differences in resilience, or why some people are more affected by negative life experiences than others.

While it is well-known that parents influence their offspring via the genetic material they pass on, it is becoming increasingly recognized that parents can also influence their offspring via non-genetic mechanisms. To date, studies have focused on the influence of a single parent on their offspring, despite the biological reality that mothering and fathering co-occur in most organisms. The goal of the proposed project is to examine the joint influence of mothers and fathers on offspring behavior in threespined sticklebacks (Gasterosteus aculeatus), a small fish in which the father is solely responsible for parental care. One of the advantages of studying sticklebacks is that the non-genetic influence of mothers and fathers on offspring is disassociated in time and occurs via different mechanisms: mothers influence offspring early in development via material in the eggs, while fathers influence offspring via their parenting behavior. The proposed studies will reveal whether non-genetic parental effects on offspring behavior can be adaptive, and help to prepare offspring for survival in a dangerous environment. In the spirit of this grant, a public outreach project with a local Boys and Girls Club has been initiated to study wildlife behavior with 8-10 year-old children, many of whom have been affected by the issues that are studied in the grant (foster care, adoption, differences in parenting styles, etc.), and who have had few opportunities to engage in science. The end result of this collaboration will be a handbook for basic behavioral experiments that are appropriate for this age group. The proposed activity will provide training and outreach opportunities for many undergraduates, a graduate student and one Postdoc, Understanding how mothers and fathers combine to shape the behavior of their offspring in sticklebacks can be used as a model for the influence of parents on offspring in other species, including humans.

These studies aim to understand how flexibility in parenting behavior and effects of parenting on offspring behavior and physiology (parental effects) influence evolutionary patterns using the threespine stickleback fish as a model. Threespine stickleback originated in marine environments and have colonized freshwater multiple times. In some cases, the exact age of freshwater populations is known, providing a unique opportunity to study not only the mechanisms underlying how variation in parental care influences offspring in multiple environments, but also examination of the speed at which these changes are occurring. Current ecosystems and habitats are rapidly changing in response to climatic and anthropogenic influences, and the proposed series of studies provides an opportunity to observe how parental behavior and parental effects facilitate rapid, adaptive evolution. While many studies of parental effects, including on humans, focus on the effects that mothers have on their offspring, in threespine stickleback, the father is the sole provider of parental care. Therefore these studies will provide insight into how fathers influence their offspring, and will determine whether the influence of mothers and fathers on offspring is similar or different.

Consistent individual differences in behavior, analogous to personality in humans, are ubiquitous throughout the animal kingdom. Animals can serve as models to study the evolutionary and ecological causes and consequences of personality in ways that are not possible in human psychology. For example, researchers interested in differences in boldness, aggression, and exploratory behavior have studied a fish, named the three-spined stickleback, that has a relatively short lifespan and is easy to care for. Previous studies have shown that different personalities of three-spined stickleback occur in different habitats and social environments in nature. The goal of this project is to determine 1) whether the personality of an individual is shaped by their environment, i.e. via plasticity; 2) if certain personalities consistently use certain environments over time (for example, if bold individuals always occur in large social groups); and 3) whether individuals tend to occur in environments for which they are well-suited. The project comprises an intensive laboratory-based experiment and a large-scale study of three-spined stickleback in their natural environment to provide a complete understanding of why some personalities are more likely to occur in certain habitats or social environments. This work has important implications for understanding why animals, including humans, show such marked variation in behavior that is consistent across time or context. This project provides ample training opportunities for undergraduates to become future scientists. The topic of the research, especially the field component, is highly accessible to a general audience and will be presented as science-in-action to local citizens and vacationers throughout the field season in rural Mendocino County, CA.

Data from this project will be made available in the Dryad Digital Repository (datadryad.org).

? DESCRIPTION (provided by applicant): Our understanding of fathering has lagged far behind our understanding of mothering, yet fathers have a substantial impact on the well-being of their offspring. The overall objective of this application is to understand the behavioral, molecular and epigenetic mechanisms that contribute to the effects of fathering on offspring. The central hypothesis is that fathering, like mothering, has long-lasting, transgenerational consequences for offspring behavior that are mediated via epigenetic changes in the genome that influence brain gene expression. The rationale that underlies the proposed research is that studying natural variation in social behavior in a tractable vertebrate system with sophisticated paternal behaviors is likely to have success identifying the causes and consequences of fathering in other organisms, including humans. There are two specific aims: 1: Identify the sensitive period and the molecular mechanisms underlying the effect of fathering on offspring. The working hypothesis for this aim is that fathering influences offspring gene expression during a sensitive period in development that has consequences for offspring behavior later in life. 2: Identify the epigenetic modifications caused by fathering. The working hypothesis for this aim is that fathering causes epigenetic modifications to the genome that influence offspring brain gene expression, behavior and stress physiology. The expected outcome of this project is a detailed understanding of the basic mechanisms by which family environments created by different fathering styles exert protective effects on offspring. These outcomes are expected to have an important positive impact because understanding the impacts of fathers on offspring could enhance the development of interventions that promote the adoption of healthy behaviors. The contribution of the proposed research is expected to be a detailed understanding of the behavioral, molecular and epigenetic mechanisms by which fathers influence their offspring using a new model system for fathering. This contribution will be significant because it will reveal if fathering, like mothering, can influence subsequent generations via epigenetic modifications to the genome. The proposed research is innovative because it utilizes a new genomically-enabled model organism in which fathers are the sole providers of parental care (threespined stickleback fish). The benefit of using a system with sole paternal care such as sticklebacks is that we can isolate the effects of fathering from the effects of mothering.

Within the study of animal behavior questions remain concerning why population variation in behaviors exist, why individuals sometimes show consistent behavior across time while at other times they do not, and last why we see certain behaviors occurring together within individuals, or the expression of animal personalities. Behavior is controlled by genes and there are a number of ways in which researchers can ask questions about behavior and the genes that control their expression. However some of our most valuable investigative techniques, and the data they produce, are not easily integrated. This is a significant missing piece to our full understanding of how genes control behaviors. Here a workshop will bring together researchers from a wide variety of areas within behavior and genetics to address this missing integration to determine how data can be brought together and develop training plans and recommendations for current and future researchers in the area of genetics and behavior. Outcomes from this workshop will be broadly disseminated to the scientific community through publications and are of benefit not only to the behavioral sciences but to studies of ecology, evolution, neuroscience, and physiology - including human health.

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. The Abstract is unchanged. Parental care is critical to the health of both parents and offspring, yet little is known about how molecular substrates act within brain areas and neuronal circuits to alter parental behavior, and this gap is especially wide for paternal care, i.e. the care-giving behavior of fathers. The proposed research capitalizes on natural variation in paternal care within a single species (threespined stickleback fish) to uncover the biological basis of paternal care in vertebrates. The current models for paternal care have biparental care, which makes it difficult to disentangle the behavior of mothers and fathers. Three-spined stickleback fish are a promising new model for paternal care because fathers are solely responsible for providing care. Moreover, the molecular mechanisms related to care are deeply conserved in vertebrates, the stickleback genome is small and compact and there are a growing number of functional tools available to study them. The goals of this proposal are to define the molecular elements responsible for differences in paternal care within a single species and to characterize the neurobiological pathways involved in such variation in behavior. There are two objectives: 1) Identify genes that contribute to differences in paternal care and test their function; 2) Define the ways in which neuropeptide signaling regulates paternal care. The project combines brain gene expression profiling at the bulk and single cell level, viral mediated transgenesis experiments to establish mechanism and pharmacological manipulations of oxytocin and arginine vasopressin signaling. The proposed work offers an innovative solution to the challenge of dissecting the biological basis of paternal care by using a powerful new model for fathering, and by capitalizing on natural variation in paternal care within a single species.