William Smotherman - US grants

One of the clear implications of psychobiological research is the importance of early events in shaping subsequent development. Observation and manipulation of rodent fetuses has permitted investigation of the process of prenatal behavioral development, and has traced the developmental origins of learning and memory to the prenatal period. The fetal rat model presents advantages over neonatal study, because the fetus lacks experience with stimuli associated with suckling or maternal behavior. The fetus also can be maintained in an experimental setting that does not require active behavioral care by the mother. The rat fetus provides a simple mammalian system for experimental investigation of how associations are acquired and memories are stored within an incomplete nervous system that undergoes constant and rapid change during early ontogeny. Prenatal sensory experience is controlled by presentation of stimuli to individual fetal subjects against a relatively stable sensory background. This proposal introduces tactile and chemosensory stimuli that mimic important features of the neonatal environment, including an artificial nipple and milk. These stimuli reliably evoke behavioral and physiological responses from naive fetal subjects, including activation of the fetal opioid system by milk, and can support fetal learning through their association. Opioid activity also can be manipulated by administration of selective agonist and antagonist drugs to individual fetal subjects. Responses of the fetus are measured by observing motor behavior, including coordinated action patterns. Species-typical motor responses will serve as behavioral bioassays for measuring opioid involvement in fetal associative learning and memory. This program of research will investigate (a) the acquisition of conditioning, (b) the specificity of fetal responses to the artificial nipple, (c) effects of conditioning on opioid responses evoked by milk, (d) memory and retention of experiences with the nipple, and (e) ontogenetic changes in opioid involvement in fetal learning. The use of ecologically relevant and developmentally appropriate sensory manipulations to study fetal learning provides a means for quantitative assessment of the integrated output of the developing nervous system in the intact animal.

Concern for the healthy development of the fetus continues to spawn considerable interest in prenatal behavior, yet relatively little is known about how a fetus behaves and responds to changes within its uterine environment. In spite of technological advances, methodological problems and ethical considerations have limited the study of the human fetus to indirect monitoring and postnatal inference. Therefore, direct observation and experimentation is possible only with nonhuman subjects. Recent technical developments now enable precise manipulation of the intrauterine environment of the rat fetus and observation of fetal behavior in utero. With the pregnant female rat surgically prepared by reversible spinal anesthesia and her uterus externalized into a warm saline bath, the intrauterine environment can be manipulated by intra-amniotic injection, chemosensory stimulation delivered by intraoral infusion, and behavior of the fetus directly observed through the uterine wall, through the amniotic membrane, or within an unrestrained fluid medium. These procedural tools now permit study of the developing mammalian fetus in its environment. This Research Career Development Award application outlines a general program of research to investigate the behavioral biology of the rat fetus. The principal objective of the proposed program is threefold: (a) to describe the normal behavioral development of the unmanipulated rat fetus in utero; (b) to characterize the behavior of the fetus in aversive and appetitive learning situations and to explore the role of fetal learning in subsequent behavioral development; and (c) to investigate the interplay between prenatal behavior and the development of behavioral and morphological anomalies.

biomedical equipment purchase;

This conference grant application is to provide partial support of the travel expenses to a number of United States pre-doctoral and post-doctoral students for attendance at the 1990 meeting of the International Society for Developmental Psychobiology (ISDP) to be held in Cambridge, England. Additional requested funds include honoraria for distinguished, European scientists who will provide keynote addresses. Although ISDP is an international society, the meeting in 1990 will be the first meeting of the Society to be held abroad. This meeting will provide a special opportunity to foster further interaction between developmental psychobiologists in the United States with those in the international community that have a somewhat different research perspective, a goal consistent with the international designation of the Society. At this 23rd annual meeting it is hoped that one of the important characteristics of the Society can be retained--the tradition of active student participation in the annual meeting.

Newborn mammals must acquire milk to survive. The stretch response, an example of species-typical motor behavior that typically occurs during suckling at the nipple, recently has been identified in the rat fetus. Using techniques that permit direct observation of healthy rodent fetuses and controlled presentation of chemosensory fluids to fetal subjects, it is now possible to apply experimental methods to study the stretch response and other aspects of behavior of the developing mammalian fetus in its environment. Because the fetus lacks specific experience with milk and does not require milk for its sustenance, responsiveness to milk can be studied in naive subjects over a range of prenatal ages. Moreover, study of the fetus obviates some of the complexities of studying the newborn, which by necessity must be removed from its homeostatic relationship with the mother to permit measurement of motor and sensory abilities. The prenatal period thus provides a unique testing ground for investigating the control and development of behavioral patterns that become functionally important after birth. Study of the fetal stretch response will serve as an animal model of prenatal motor development with direct relevance for postnatal behavior. In this proposal, we will: (a) investigate sensory factors that influence the expression of the stretch response, (b) characterize changes in motor behavior that organize the stretch response, (c) manipulate fetal behavior to promote earlier developmental expression of the stretch response, and (d) examine the interaction of fetal responses to milk and other sensory-based behavior. The concept of self-organization will be applied to the study of fetal behavioral responses to milk as a model for understanding the process of developmental change.

biomedical equipment purchase;