Sunny K. Boyd - US grants

The long-term goal is to define the mechanisms of action of the neuropeptide hormones which control vertebrate reproductive behaviors. The current proposed research represents a novel approach to the long-standing problem of understanding the precise role of sexually dimorphic neural structures. There is strong evidence for structural sexual dimorphism in the brains of vertebrates as well as behavioral sexual dimorphism. What is not known is the link between these two observations. Since the neuropeptide arginine vasotocin (AVT) is a potent activator of behavior, examining the sexual differentiation of this neuroendocrine system may provide this missing functional link between anatomical structure and behavior. The specific goals of the proposed research are (1) to determine whether gonadal steroid hormones influence the concentration of AVT in specific brain areas of adults, (2) to determine whether the presence of the gonadal steroid hormones during development is required for differentiation of the central nervous system AVT pathways, and (3) to determine whether experimental changes in sex steroid levels alter the distribution or density of AVT receptors. Concentrations of peptide hormone in specific brain areas will be measured using the combined techniques of microdissection and radioimmunoassay of brain tissue. Brain receptors for AVT will be localized and quantified using in vitro autoradiography which is uniquely suited to study of receptors in small neural regions. Correlative studies of steroid-neuropeptide interactions and the use of the extirpation-replacement experimental paradigm in animals of various ages, will determine the functional relationships between these hormones in sexual differentiation. The specific animal to be used in the amphibian Rana catesbeiana. Recent evidence demonstrates that the same steroid and neuropeptide hormones control reproduction in both mammals and amphibians. However, the simplified nervous system of amphibians makes this class of vertebrates uniquely suited to studies of the neural substrates of behavior. These studies will yield insights into basic mechanisms underlying the interaction of steroid hormones and central nervous system peptide hormones. These findings will have broad applicability. Steroids and neuropeptides also interact within the brain to control cardiovascular function and memory processes, for example.

Vicki J. Martin DUE 9552116 University of Notre Dame FY1995 $ 50,000 Notre Dame, IN 46556 ILI - Instrumentation Project: Life Sciences Title: New Visions: Advanced Optical Imaging for the Undergraduate In an increasing effort to expand improvements in undergraduate training, the Department of Biological Science at Notre Dame is initiating a program to integrate advanced bioimaging into its core curriculum. This decision is stimulated by a pressing need to incorporate innovative methods for recording, quantifying, and analyzing biological processes. In addition, new technological advancements in applied optics, electronic imaging, and computational-based image processing continue to drive the frontier of biomolecular imaging into all elements of our lives from medical diagnostics to science education and research. Clearly, if we plan to stay at the frontier of this technology, we must provide undergraduates with the opportunity to experiment, explore, and discover the power of applied optical imaging. To integrate bioimaging into undergraduate laboratories, we are carrying out a variety of experiments that combine the use of important new biosensors and molecular probes with state-of-the-art electronic detectors, high-powered confocal optics, and sophisticated software programs for the study of dynamic cell, developmental, and physiological processes. These exercises are training students in the nuts and bolts of electronic image acquisition, processing, and analysis, while emphasizing the power of computer-based digital optical instrumentation and its use as a quantitative tool for biological investigation.

9514305 Boyd There is strong evidence for sexual differences in the central nervous system, and in the physiology and behavior of most vertebrates. The steroid hormones derived from the gonads of males and females are necessary for the generation and maintenance of these differences. However, they are not solely responsible for these differences and other chemical mediators in the brain, notably neuropeptides, subserve critical functions in the manifestation of the anatomical differences. Therefore, a central issue is the definition of the interrelationship between steroid hormones and neuropeptides in the brain. The present experiments address this issue and focus on the posterior pituitary neuropeptide system, which has been implicated in fluid balance, lactation, learning and memory, reproductive behaviors, and parental behaviors. Dr. Boyd will determine whether a direct neurochemical link is possible between the steroid hormones and neuropeptide system containing arginine vasotocin and how the steroids modulate the ability of identified neurons to produce vasotocin. She will also establish the connections of these neuropeptide-containing neurons in the brain. These results are crucial to understanding the basic mechanisms underlying chemical messenger interactions in the brain. Furthermore, they will generate important information about the origin of sex differences in neuroanatomical structures and provide a basis for gender differences in behavior, prevalent in most species.

The ability to give birth to live young occurs in all classes of
vertebrates except cyclostomes and birds. In a unique order of tropical
amphibians, the caecilian amphibians, the majority of species give birth to
live young but the physiological mechanisms which control this process are
unknown. It is proposed that fetal caecilian gills function as endocrine
organs and produce hormones similar to those produced by mammalian
placentas. Such structures have not been described in non-mammals. The
goal of this project is to determine whether fetal caecilian tissues
produce steroid hormones. The methods to be used include identification of
steroid metabolites produced by tissues in vitro and localization of
enzymes known to function in steroid synthesis. Maternal steroid hormone
levels will be determined.

These studies will provide the first information on steroid endocrinology
and the control of live- bearing for this order of amphibians. They will
thus contribute substantially to understanding of reproductive biology and
conservation of these unique animals and also to hormonal control of
pregnancy in other vertebrates.

This symposium on contemporary approaches to endocrine signaling is part of the annual meeting for the Society for Integrative & Comparative Biology (SICB). It addresses technical innovations that are now being applied to unconventional model organisms. Participants in this program possess expertise in neuroendocrinolgy, endocrinology, animal behavior, and developmental biology. The symposium will engage both senior and junior ranked scientists and students in discussions of the application of these new techniques that have been derived from more traditional model organisms, such as laboratory rodents. Introduction of new people to the society is enhanced by the international nature of this meeting being held in Toronto, Canada. Travel funds will allow participants to attend the meeting.
The impact of this will extend to numerous fields of study, as mentioned above. In addition, the meeting will foster scientific education by training graduate and undergraduate students to participate in comparative biological research armed with a clear understanding of this sophisticated technology. A further impact will be made when these discussions are published in the journals: Integrative & Comparative Biology and General & Comparative Endocrinology.

Neuropeptide Modulation of a Vocal Motor Pathway
Sunny K. Boyd, Principal Investigator
Proposal Number: 0235903


The long-term objective of this research program is to identify the interactions among chemical messengers that control behaviors. Peptide and steroid hormones regulate social behaviors in representative species from all vertebrate classes. The mechanisms of action of these compounds and the site in the brain where they act on specific behaviors are poorly understood. The interaction of testicular steroids and the neuropeptide arginine vasotocin will be investigated in the vertebrate brainstem. Three experimental approaches will be used to assess the importance of these interactions in generation of vocalizations, which are a critical component of social behavior in many species. First, neuropeptide effects on the brainstem will be tested by analyzing vocalizations prior to, and following, neuropeptide administration. Second, whether the necessary anatomical conditions are met at a cellular level will be determined with tract-tracing and peptide or receptor double-labeling. Third, this project will determine whether peptide receptors in the brainstem are functional with receptor binding and electrophysiological recording techniques. Neuropeptides alter a variety of vertebrate behaviors, including parental, aggressive, and reproductive behaviors. However, little is known about the effects of these peptides at the motor output level. Findings from this research program will thus offer insight into conserved mechanisms for peptide control of behavior. These studies will provide excellent training for undergraduate and graduate students who will acquire skills at the organismal, tissue, cellular, and molecular levels. These projects will also train high school science teachers and minority undergraduates via two institutional programs.

The Department of Biological Sciences at the University of Notre Dame is sponsoring a NSF-REU Site for undergraduate research during the summers of 2005 - 2009. The focus of the proposed REU program is "Integrative Cell and Molecular Biology." The primary goals of the program are to 1) expose students to the excitement of scientific discovery, 2) help students develop the skills needed to generate, analyze and report scientific data, 3) educate students on the professionalism needed to succeed in graduate school and beyond, 4) give students opportunities for leadership roles, and 5) encourage students to be responsible scientists and citizens by providing service opportunities. To reach these goals, participants will carry out research projects for 10 weeks. During these 10 weeks, they will formulate their own research project, speak on their proposed work twice, attend and coordinate a weekly seminar program to develop professional and leadership skills, attend weekly journal clubs where students present current published research, and participate in an optional service component mentoring high school students. The underlying aim of the program is to give students strong incentives for pursuing careers in research. Information can be obtained by contacting the Dr. Michelle Whaley at Michelle.A.Whaley.3@nd.edu or by visiting http://www.nd.edu/~biology/reu/indexpageA.htm

Neuropeptides are known to regulate social behaviors in representative species from all vertebrate classes. Species differences in behavior, however, have made development of clear mechanistic models difficult. This project investigates the complexity of behavioral mechanisms using a combination of field experiments and computational models. Field studies address important emerging questions on neuropeptide modulation of female affiliative behaviors. Synthetic experiments with agent-based models allow exploration of conditions impractical or impossible in empirical tests. The models are expected to propose new mechanisms for neuropeptide control of behavior. This project thus implements a tight experiment-model-experiment loop and develops a new paradigm for a systems biology approach to understanding social behavior. Neuropeptides can alter a variety of vertebrate social behaviors, including parental, aggressive, and reproductive behaviors. Specifically, this project will determine the effects of vasotocin on female phonotaxis in gray treefrogs and subsequently a computational model for phonotaxis that can make predictions as to how neuropeptides influence social behavior will be developed. This model will then be tested under natural conditions for verification. Results from these studies will significantly advance our understanding of the effect of neuropeptides on female behavioral plasticity. This project also includes a significant training component, with involvement of an undergraduate field biology class (populated with 30% under-represented minorities) and training of a post-doctoral fellow and graduate student in a unique inter-disciplinary environment. In addition, a new course on modeling approaches to behavioral sciences will be developed.

The Society for Behavioral Neuroendocrinology is a multidisciplinary society that promotes research and education concerning hormones, the brain and behavior. The annual conference brings together scientists from many fields, with a focus on the integration of cellular and molecular concepts into functional frameworks that improve our understanding of human and animal behaviors. This grant will support significant initiatives to foster participation by undergraduate students, graduate students, and post-doctoral fellows at society meetings. Funds will support the following trainee activities: (1) Young Investigator's Symposium. Outstanding senior graduate students or post-docs are chosen to present talks in a dedicated symposium. This format recognizes the accomplishments of such trainees, facilitates their movement into more advanced positions, and motivates younger scientists. (2) Career Development Workshops. Workshops educate trainees on important career development topics and retain trainees in the sciences. (3) Travel Awards. Funding for travel to meetings is provided for trainees. This allows trainees to present their work in a supportive environment and gain exposure to the breadth and depth of the field. (4) Meet-The-Professor Lunches. Small groups of trainees have lunch and discussion with senior members of the society. Trainees thus gain insight into the research enterprise, create new relationships, and find strong mentors. (5) Trainee Poster Competition. Posters presented by undergraduates, graduate students, and post-doctoral fellows are judged, based on the scientific merit of the research, the effectiveness of the presentation and the trainee's role in the research. The competition is thus an educational experience for all and it also provides an opportunity to encourage and reward success at each level. Funding for trainee events at the SBN meeting will play a key role in the attraction and retention of the brightest and best-trained interdisciplinary scientists.

The long-term objective of this research project is to identify the interactions among chemical messengers that control behaviors. Neuropeptides regulate social behaviors in representative species from all vertebrate classes. Species differences in behavior, however, have made development of clear mechanistic models difficult. This project investigates the complexity of behavioral mechanisms using a combination of animal experiments and computational models. Field and laboratory studies will be combined to address important emerging questions on neuropeptide modulation of male vertebrate behaviors. The agent-based modeling approach is especially well-suited to address this problem. Synthetic experiments with the model allow for exploration of conditions impractical or impossible in empirical tests. The model is expected to propose novel mechanisms underlying neuropeptide control of behavior. This project thus implements a tightly controlled experiment-model-experiment loop and develops a new paradigm for a systems biology approach towards understanding social behavior. Neuropeptides alter a variety of vertebrate social behaviors, including parental, aggressive, and reproductive behaviors. Conserved behaviors and chemical messengers will make the empirical results and the model broadly applicable to vertebrates. Results will significantly advance our understanding of the effect of neuropeptides on vertebrate behavioral plasticity. This project also includes a significant training component, with involvement of an undergraduate field biology class (with a 30% minority makeup) and training of graduate students in a unique inter-disciplinary environment. The data management plan includes deposition of new software at SourceForge and archiving of digital data in the PI's institutional databases.