Mary S. Erskine - US grants

Under both natural and laboratory conditions, female rats in estrus exhibit spontaneous and predictable patterns of sexual contacts with males which appear to regulate or pace the temporal characteristics of copulatory stimuli received. Two consequences of the females' pacing of copulatory stimulation are an abbreviation of the length of the period of estrus and acute increases in serum concentrations of the 5a-reduced androgen, 3a-androstanediol. These data suggest that this androgen, released from the ovary in response to temporally-appropriate coital stimuli, contributes to decreasing sexual responsiveness at the end of estrus. The experiments proposed in this application will define the characteristics of the behavioral stimuli which contribute to estrus abbreviation and 3a-androstanediol release, determine whether increases in circulating 3a-androstanediol play a physiological role in estrus abbreviation, and determine whether increased levels of 3a-androstanediol are a result of pituitary hormone release. These studies will examine the reciprocal relationships between the endocrine system and sexual responsiveness in the female rat -- which relationships may serve to regulate reproductive processes insuring species survival. In addition, these studies will elucidate whether 5a-reduced androgens, known to have strong inhibitory effects on sexual receptivity in ovariectomized hormone-primed rats, play a role under physiological conditions in modulating the display of sexual behavior in the intact female rat.

PI: Erskine, Mary S. Proposal Number: IBN-9722804 Advances in molecular biology have led to the understanding that certain genes, called "immediate early genes" become expressed when cells become active. Techniques have been developed to mark the cells expressing these genes, including the cells of the central nervous system. This symposium presents the work of scientists in several areas of behavior and neuroscience as examples of the use of this technique to mark systems in the brain that are responsive to different types of sensory signals or are involved in controlling a variety of behaviors. By holding the symposium in conjunction with a national scientific meeting, the organizers make information about this technique and its use in behavioral research available to researchers and their students in a wide range fields.

DESCRIPTION (adapted from applicant's abstract): In many female mammals, vaginocervical stimulation (VCS) received during mating modifies sexual responsiveness and initiates or induces several neuroendocrine changes which influence reproductive success. VCS is required in rodent for initiation of the endocrine changes of early pregnancy or pseudopregnancy (PSP), in particular twice-daily surges of prolactin (PRL) secretion which maintain corpus luteum function. The particular characteristics of the VCS received by the female during mating are critical determinants of whether PSP will occur, and there is a unique correspondence between the pattern of VCS which the female requires for initiation of pregnancy and the patterning of copulatory stimulation received by the female during mating. Therefore, this model system offers an opportunity to examine at the cellular level how the expression of behavior can influence neural function over a prolonged period. Despite advances in our understanding of the endocrine mechanisms responsible for PSP, our knowledge remains incomplete, particularly in the area of the initiation phase of the PRL surges. Recent work from the PI's laboratory has shown that a productive approach to the question of how mating stimulation initiates PRL surges is to use naturally-occurring patterns of coital stimulation to evaluate changes in neural function which are specific to PSP. Research carried out during the tenure of this grant will explore the proximal neural and endocrine changes which occur in response to VCS in several areas of the brain which the investigator's have identified to be involved in the process by which VCS is transduced into the PRL surge of early pregnancy/PSP. Experiments will: 1) determine which specific PRL responses to mating are responsible for PSP; 2) explore the role of the medial amygdala in transducing the afferent genitosensory input into the neuroendocrine changes of PSP; 3) examine whether ascending noradrenergic fibers are involved in initiating changes within the medial amygdala necessary for PSP; and 4) examine the role of oxytocin neurons in the paraventricular nucleus in the induction of PRL urges by mating. The broad research goal of this Independent Scientist Award application is to use neuroethological approaches to define the cellular mechanisms by which mating behavior initiates neuroendocrine responses of early pregnancy.

DESCRIPTION (provided by applicant): In female rats, vaginocervical stimulation (VCS) received during mating or parturition modifies sexual and maternal behavior and induces neuroendocrine changes which influence reproductive success. Mating is required to initiate the endocrine changes of early pregnancy, in particular, the twice-daily surges of pituitary prolactin (PRL) secretion which occur for the first 10-12 days of pregnancy or pseudopregnancy (PSP) and which maintain ovarian progesterone secretion. The particular characteristics of the VCS received by the female during a natural mating sequence determine whether PSP will occur, and both the number and the timing of intromissions received by the female have been shown to influence the initiation of the PRL surges. Data suggest that active patterning or pacing of VCS by the female during mating is critical for processing and storage of genitosensory inputs and that the intermittent and discontinuous stimuli resulting from paced mating maximize the likelihood that sufficient amounts of stimulation accumulate in brain for PSP. We have hypothesized that expression of these PRL surges is dependent both upon summation of individual stimuli throughout a single episode of mating and upon longer-term changes which perpetuate the expression of PRL surges over the subsequent 10-12 days. Previous work has characterized the natural mating stimuli which are optimal for induction of the PRL surges, determined which specific changes in PRL secretion are the direct consequence of such stimulation, established that the medial amygdala (MEApd) is an important integrative center for this response, and begun to examine whether and how glutamatergic and noradrenergic neurotransmission within the MEApd are involved in establishment of the neural mnemonic required for PSP. The experiments outlined in this application will use this model system to address the broader questions of how sensory stimulation is filtered to maximize retention of information and how sensory input induces neural plasticity which may alter brain function over the long term. This Independent Scientist Award renewal application proposes that the PI learn confocal microscopy with stereological precision and that she undertake a collaborative electrophysiological study examining responses of MEApd neurons to repetitive VCS. This plan will facilitate short-term goals (confocal work) and will explore avenues for addressing long-term research goals (electrophysiological project).

This Undergraduate Research Opportunity Program (UROP) at Boston University awards Summer Undergraduate Research Fellowships (SURF) to undergraduate students, especially those from underrepresented minority groups. Ten students will be provided support for a 10-week research experience each year. The main objectives of the program are to 1) provide students with a research experience that takes advantage of modern cross-disciplinary approaches in the STEM disciplines; 2) train students in research methods, scientific ethics, and the scientific culture; and 3) encourage underrepresented minority students to continue their education through graduate school. Applications from well-qualified students within all STEM disciplines (Science, Technology, Engineering and Mathematics) including Computer Science are welcome. The research projects available to students use cross-disciplinary approaches to biological problems. Chemical, computational, and engineering methods are applied to developmental, molecular and neurobiological scientific questions. As a result, students will acquire in-depth knowledge of a number of related areas and learn the varied skills needed to integrate information from several disciplines. Exposure to a diverse set of projects will also aid the student in determining potential research areas they might like to pursue in graduate school. Students will be matched to research teams consisting of a faculty mentor and a graduate and undergraduate student within the mentor's lab. Students will give two oral presentations during the summer and will return to Boston University in the fall semester to present the results of their research in poster format at the university's Undergraduate Research Symposium. Additionally, they will attend weekly summer workshops on scientific publication, graduate school admissions, and scientific ethics. Social events designed to integrate students into the research environment are included throughout the summer experience. Research stipends, housing and travel are provided. More information is available from Professor Mary Erskine, Director, and Jeremy Goodman, Assistant Director, UROP, 617-353-2020, urop@bu.edu, or by visiting http://www.bu.edu/surf.