Warren G. (Ted) Hall - US grants

Three analyses of the behavioral and neural organization of early learning are proposed. These studies continue an ongoing investigation of appetitive behavior in developing rats that has: (a) defined an emerging and experience-vulnerable response system for rooting, probing, search, and exploration; (b) uncovered a system of unilateral olfactory learning underlying one component of learning; and (c) correlated developmental changes in this unilateral learning with specific events in neural maturation. A further characterization of the development and plasticity of an appetitive response system forms specific AIM #1 of this application. Experiments are proposed to trace the development of rooting/probing/search behaviors (in both the normal and a con- trolled environment; and to explore the manner in which experience modulates, disturbs, or is integrated into this developmental system. These studies broadly assess the developmental continuity and significance for later mammalian behavior of a primitive adaptive system. Experiments of Specific AIM #2 will analyze the early neurobehavioral organization of Pavlovian conditioning using the unilateral conditioning paradigm. They will assess the conditions under which unilaterally stored memories can be transferred and study the independence of specific conditioning processes. In Specific AIM #3, the neural substrates of early learning will be studied by determining which developing pathways are critical for developmental changes in unilateral conditioning and by mapping changes in neural activity occurring with learning and memory access. Transection techniques will be used to isolate pathways end deoxyglucose autoradiography will be used to help identify neural substrates of learning (applying a recently developed composite-comparison technique that produces topographical maps of differences in neural activity between groups of brains). These projects are broadly relevant to understanding mechanisms of appetitive learning. Moreover, they may have specific applicability to understanding disorders in learning that develop from inappropriate experience or disturbances in neural maturation.

I propose studies of the development of ingestive behavior. Ingestion is one of the few behaviors that can be studied from birth throughout the life of altricial mammals. As such, it provides a powerful tool for the analysis of behavioral and neural development. These studies will take advantages of techniques that we have developed for study of developing ingestive system of rats, away from the suckling situation. Our tests allow tight experimental control and avoid potential problems created by the special nature of suckling. Specifically, the development of (1) sensory modulation, and (2) physiological controls of ingestion will be studied. Sensory deprivation may contribute to the effects of food deprivation procedures, and this potential factor in the development of ingestive behavior will be investigated (3). In addition, I will assess the importance of specific and defined early oral experiences (4). These studies continue to examine a behavioral system for early ingestion that appears to be the precursor to adult ingestive behavior. It is a system which can provide a unique study arena for assessing neural and behavioral development. I propose here to begin relating brain development to behavioral changes in the developing ingestive system. One initial approach will utilize brain transections, a second, measurement of regional brain metabolic activity using the 14C-2DG autoradiography technique. The proposed projects treat ingestive behavior in pups as a general model of motivational development. Thus, they may provide a representative ontogenetic analysis of a system in which behavioral and neural development can be examined and integrated.

This competing continuation application for an ADAMHA Research Scientist Development Award (Level II) proposes studies of the ontogeny of ingestion and its behavioral, physiological, and neural organization. The proposed experiments exploit a developmental system of independent ingestive behavior (devised and described by my lab) and techniques for systems-level, neural analysis recently developed for infant rodents. The control of individual components in the ingestive sequence will be studied in young rats. Emphasis will be placed on the oral response component and in particular on the decrement in oral responsiveness that occurs during feeding experience. This intrinsic, habituation-like mechanism may be a principal integrator of ingestion-related signals. An integrative function for oral habituation would be indicated by influences of physiological state and postingestive signals on habituation parameters such as the initial level of responsiveness, rate of decrement, or duration of decremented responsiveness. The relation of the oral component to earlier components in the sequence will be assessed in experiments measuring olfactory orienting, and the brainstem representation of the oral habituation process will be evaluated in decerebrate pups. The proposed experiments offer a unique conceptualization of ingestion that may contribute to a new, more complete, understanding of feeding control. These experiments will extend our ontogenetic analysis of an appetitive system, one that can be followed from birth and manipulated in a controlled fashion, and in which maturing neural systems can be related to changes in behavioral organization.

A developmental strategy will be applied to the behavioral, physiological, and neural analysis of early independent ingestion in rats. The proposed experiments make use of a species that undergoes a remarkable postnatal neural maturation and related behavioral ontogeny, each compressed into a time period that is practical to investigate. The use of developmental analysis provides unique opportunities to learn about the initial neurobehavioral organization of early appearing systems such as those for ingestion. The proposed research will: 1) define behavioral characteristics of the initiation, guidance, and maintenance of early independent ingestion and its related affective features; 2) investigate the ontogency of specific controls of ingestion and ingestion-related affect; 3) study the systems for gastric control of ingestion by taking advantage of simplifications provided by the immaturity of young pups; and 4) study the neural basis of early ingestion and its control using decerebrations and deoxyglucose autoradiographic techniques. An improved understanding of the origins of independent ingestion and its neural basis in rats may contribute to understanding ingestive processes in other species, and to insights about feeding and feeding pathologies in humans. Since ingestive behavior is one of the few complex appetitive behaviors present throughout life, these experiments also have a more general significance, that of providing a representative ontogenetic analysis of a "model" motivational system.

This award provides funds to the Undergraduate Neurosciences Program at Duke University to establish an NSF-REU site which will support a Summer Undergraduate Research initiative. The program emphasizes integrative, systems, and behavioral neuroscience, reflecting the breadth of neuroscience research at Duke University. Research, and training experiences will be organized around the theme of "mechanisms of behavior", capitalizing on the strengths of the present academic Undergraduate program and targeting laboratories in which supportive and stimulating research environments are found. Duke University has a history of successful summer research programs, especially those that provide training experiences for women and minorities. The mentors have drawn form this experience in developing the present program, and are able to make use of existing administrative structures both for recruiting candidates to the program and for providing the logistical support necessary for an engaging and stimulating research experience.

9322288 Hall This award provides funds to the Undergraduate Neurosciences Program at Duke University plans a summer research program for undergraduates who will have the opportunity to become involved in neuroscience research at a major university Research and training experiences will be organized around the theme of "Mechanisms of Behavior" The emphasis on integrative, systems, and behavioral neuroscience that unifies faculty research interests within this interdisciplinary field at Duke serves as the common theme for the individual projects available to student participants in the program The focus of the ten week summer program for each student will be a research mentorship with a participating faculty member Three weekly seminar series -- "Research in the Neurosciences," "Science Basics," and "Science Ethics and Practice" -- will be included in the summer schedule "Research in the Neurosciences" will focus on ongoing faculty research so that students gain exposure to the field of neuroscience research beyond their own mentor's specific interests "Science Basics" will address practical matters pertaining to science careers"Science Ethics and Practice" will bring in outside speakers to address ethics issues such as fraud and animal welfare, and will also involve panel discussion of practical topics such as balancing career and family, life as a science graduate student, and continuing research as an undergraduate The summer program will begin with a two day Orientation Conference and will close with a Research Forum at which students present their results Applications to participate in "Mechanisms in Behavior" will be accepted from sophomore undergraduates. The Program is especially interested in receiving applications from undergraduates at liberal arts colleges. ***

DESCRIPTION: Goal-seeking appetitive behavior characterizes motivation. Despite its importance in systems from basic biological desires to complex achievement drives, the developmental origins of appetitive behavior are poorly understood. Recent studies of the development of feeding and drinking in rodents have shown that the oral reflexes for licking, lapping and swallowing are present from birth. These consummatory responses are under physiological control shortly thereafter. Dehydration, in particular, is a potent stimulus for intake of oral infusions in neonates. Nonetheless, new findings from the principal investigator's lab suggest that for at least one basic appetite, the drinking stimulated by cellular dehydration, goal-seeking appetitive behavior is only acquired by post-weaning experience in which the appetitive response is linked to physiological state. Appetitive components of other motives may similarly depend on specific learning experiences. The experiments of this proposal take advantage of the relatively well understood fluid balance and drinking system as a model with which to examine the emergence of the appetitive components of motivated behavior. The critical events for the acquisition of cellular-dehydration-induced drinking will be determined and the emergence of this appetitive response will be compared to the appetitive response for extracellular dehydration. Then the stimulus control of early appetitive responding will be examined and the nature of the acquired behavioral response explored. These experiments will guide a further initial analysis of the contribution of learning to the appetitive responses for feeding behavior. As a whole, this series of experiments should reveal the conditions for the acquisition of simple appetites, evaluate processes underlying this learning, and explore the ubiquity of the acquisition of appetitive components of motivated behavior.