Lynn Nadel - US grants

This award provides funds to a group of neuroscientists at the University of Arizona for the purchase of a computer, networking hardware, and associated software. This equipment will be used to analyze experimental data resulting from comparative studies of olfaction and spatial orientation in lower and higher animals. Though collaborations with mathematicians, these investigators plan to generate models for nerve cell interactions that appear fundamental to these processes. Models will be based on anatomical and electrophysiological properties of the nervous system. Other models will have an explicitly behavioral basis. The models will developed using a neural network simulation program called GENESIS and the computer. Interspecific comparisons have traditionally provided a useful tool in understanding the underlying mechanisms of biological processes. Increasingly, the use of experimental data and theoretical schemes for the synthesis of models that make detailed predictions has played an equally important role in modern biology. Olfaction and spatial orientation are both problems of nervous integration that have interested neurobiologists for some time. The use of computational models, in particular neural network models, to get at the underlying integrative mechanisms is a promising approach to these classical problems.

A group of institutes, centers, and universities throughout the country will sponsor a summer school in Santa Fe, New Mexico during June 1990. The goal of the summer school is to provide graduate students and postdoctoral fellows with an introduction to the study of "complex" behavior in mathematical, physical, and living systems. The themes for this year's summer school will be: (i) the nature of chaos, disorder, or randomness in a variety of physical and mathematical systems; (ii) pattern formation in physical, chemical and biological systems; and (iii) cognition and computational approaches to brain and cognitive function. The four-week school will consist of short courses together with seminars, computer workshops, and laboratory projects supplementing the lectures. The material presented at the school is intended to be appropriate for advanced students with graduate-level training in the mathematical, physical, biological, or computer sciences and a strong mathematical background.

DESCRIPTION (Adapted from the Applicant's Abstract): The purpose of the present training grant is to support the holding of the Complex Systems Summer School in Santa Fe, New Mexico. The goal of the Summer School is to provide an introduction to the study of "complex" behavior in mathematical, physical and living systems as part of an interdisciplinary effort to promote the understanding of complex systems. At each school, a set of lectures and seminars is provided by leading researchers in diverse fields unified by their use of complex systems analysis. The present training grant was awarded on the assumption that students in the neurosciences would benefit from exposure to a diverse set of scientists using dynamical systems methods in approaching their specific research interests. In order to carry out this mandate we make certain that a significant proportion of the students admitted to the School have an interest in neuroscience, biology and neural networks research. The school itself evolves in response to the experiences of the previous years, and evaluations provided by the students. We will continue to employ a feature designed to help students benefit from the entire range of topics - a set of tutorials at the start of the school to provide students with a basic "toolkit" in areas such as evolution, computation, dynamical systems theory and chaos, disordered systems, information theory, neural nets, and neuroscience. Two new features have been added in recent years: first, students are organized into research groups on a variety of topics in the first week. These groups meet regularly throughout the month, planning and carrying out computational projects when possible. In the final week groups make reports. Second, we have introduced some thematic structure to the choice of lecturers. Each week two related lecture series will be offered, with related seminars in the afternoons. Our long-term goals for the school are to provide a framework within which neurobiologists, and others, can learn from each other, and can benefit from methods and techniques pioneered in diverse fields of study of complexity.

The international conference on Down syndrome will be held in the United States under the auspices of the National Down Syndrome Society. The conference will be convened under the direction of the NDSS Science Advisory Board, in collaboration with a Conference Organizing Committee. The meeting will review and document the current status of research on behavior and cognitive function in Down syndrome, including an overview of current neuroscientific research and the use of animal models. It will also review current knowledge about applying research findings to early stimulation and education programs that aim to optimize the status of individuals with Down syndrome. Finally, it will explore the directions that future research of this disorder should take. Plenary sessions will be organized in terms of five developmental stages, with each covering a variety of major topics including: 1. neurobiology and animal models 2. cognitive development and function 3. learning and memory capacity 4. language development and function 5. motor development 6. social behavior and emotional development 7. patterns and mechanisms of developmental change. There will also be a poster session for scientists to present work on specific related topics. This session will be particularly focused on younger investigators. The meeting will provide an opportunity for participants to interact with colleagues, synthesize and share knowledge, develop new collaborations and generate ideas about practical applications. This opportunity should facilitate progress in research and practice on Down syndrome.

[unreadable] DESCRIPTION (provided by applicant): The Research Conference on Cognition and Behavior in Down Syndrome will be held in the United States under the auspices of the National Down Syndrome Society (New York, NY) and the Down Syndrome Research Foundation (Vancouver, BC). The conference will be convened under the direction of the NDSS and DSRF Science Advisory Boards, in collaboration with a conference organizing committee. [unreadable] [unreadable] The meeting will review and document the current status of research on cognitive function and behavior in Down syndrome, including an overview of current neuroscientific research and the use of mouse models. It will also review current knowledge about applying research findings to early stimulation and education programs that aim to optimize the functioning and status of individuals with Down syndrome. Finally, it will explore the directions that future research on this genetic condition should take. [unreadable] [unreadable] Plenary sessions will focus on the link between Down syndrome-specific and non-Down syndrome-specific research, the state of the art in research on cognition and behavior, motor skill development, functional MRI imaging, and dementia and memory across the lifespan. [unreadable] [unreadable] Paper presentations and working groups will address the current status of research in the areas of imaging, sleep and memory, mental health, mouse models, speech and language and positive behavioral support. Research priorities and potential areas of collaboration in these key areas will be determined by working groups and shared with the entire audience. [unreadable] [unreadable] There will also be a poster session for scientists to present work on specific related topics, as well as on more broad-based Down syndrome research. The conference will provide several opportunities for participants to interact with colleagues, synthesize and share knowledge, develop new collaborations and generate ideas about practical applications. The ultimate goal is for this conference to facilitate progress in research and practice on cognition and behavior in Down syndrome. [unreadable] [unreadable] [unreadable]

The extent to which memory preserves an accurate record of the past has been debated for over a century. The veridical memory view assumes that once memory consolidation is complete, memory is stable and no longer subject to change. Furthermore, the neurobiological processes responsible for consolidation involve strengthening, but not modification of a memory. Others have argued that memories are not fixed, but instead are transformed over time as a function of experience. Mounting evidence suggests that when memories are reactivated they become labile and open to change. Retrieval can reinforce the reactivated memory, or update it through the incorporation of new information. Such transformed memories then undergo a time-dependent re-consolidation process. Although the consolidation account, emphasizing strengthening and stabilization, was the de facto paradigm of research on memory dynamics in both psychology and neuroscience for many years, there is now increasing evidence that stable memory is the exception, not the rule. Until recently we have lacked experimental approaches to systematically address memory malleability, hence the mechanisms controlling memory updating remain obscure. Furthermore, despite the extensive literature on memory reconsolidation in animals, studies in humans are rare. Drs. Lynn Nadel, Rebecca Gomez, and Almut Hupbach at the University of Arizona have developed a research paradigm for investigating reconsolidation in episodic memory, a form of memory that allows for the conscious recollection of events. This research raises important questions having to do with whether updated memories are transient or long lasting and whether the effects occur only for new memories or for old memories as well. There is also the question of what factors trigger memory reactivation, whether these factors are affected by the strength of the original memory, whether the strength of these reminders diminishes over time, and whether implicit reminders differ from explicit ones in the extent to which they affect updating of an existing memory. With support from the National Science Foundation, Drs. Nadel, Gomez, and Hupbach will address these questions. They will conduct a series of experiments in which human volunteers will learn a set of objects and two days later will be reminded of the first session or not, then immediately afterwards will learn a second set of objects. After an additional two days, participants will be asked to recall the first set only. The extent to which reminded participants recall objects from the second set when trying to recall the first set, as compared to participants who are not reminded, is an index of memory reactivation and the subsequent reconsolidation effect.

Reconsolidation, and the underlying instability it reveals, demonstrates the essential transformative nature of memory systems and could help us understand a variety of memory malleability phenomena studied broadly in human cognition, as well as the updating of prior knowledge more generally. The work will explore conditions under which memory reconsolidation is observed in human episodic memory and would support the view that memories are dynamic, not fixed, and that they can be changed as a function of subsequent experience. The work will further show how such updating is affected by the age of a memory, by the nature of the reactivating event, and by the way in which memory itself is accessed at some subsequent time. Such details will begin the process of defining the critical determinants of human episodic memory dynamics. Knowledge about how memory is changed over time, and by experience, has profound implications for everyday life, influencing assumptions made within legal and clinical settings about what counts as normal memory. Understanding memory dynamics is also important for identifying the conditions affecting the updating of prior knowledge in learning and cognitive development, both in early childhood and across the lifespan. Understanding such conditions could have a profound effect on theories of cognitive change, on understanding when normal change goes awry and could also have implications for learning in educational practice.

Recent work in language acquisition and cognitive development shows remarkable learning abilities in infancy. Much of the theoretical development in these fields is based on effects measured immediately after a learning experience, however, sleep is instrumental in transforming specific details of what is learned to a more abstract memory (Gomez, Bootzin, & Nadel, 2006; Hupbach, Gomez, Bootzin, & Nadel, 2009). The ability to abstract away from the specific details of a learning experience is crucial for infants who must be able to summarize and apply key aspects of a learning experience to novel scenarios, much like being able to abstract the block letter "A" to cursive. If memories are too specific infants will not be able to connect prior learning to new scenarios with slightly different information. A more abstract memory can more easily be applied to a wider range of information. A first project will investigate the means by which sleep leads to abstraction. A second project investigates how sleep-dependent memories are connected across time in an attempt to understand how knowledge is amassed over multiple learning experiences. Polysomnographic recording will provide information about how sleep-dependent memories are consolidated in the developing infant brain.

The proposed work is unique in bridging three areas of research: language acquisition, memory, and sleep. It has potential to be transformative to the degree that it 1) impacts language learning theories (to date based on results obtained immediately after a learning experience, not taking the changes associated with intrinsic sleep and memory processes into account); 2) the way empirical learning research is conducted (to scale up to the constraints of real-world learning researchers will need to begin to measure time-dependent effects); and 3) informs us about the relationship between phases of sleep and memory formation in the developing infant brain, dynamics that could have a profound effect on theories of language and memory change, on understanding when normal change goes awry, and for learning in educational practice. In addition to the practical benefits for society, the proposed work has benefits closer to home with training of undergraduate students a significant part of the grant. These students will gain extensive one-on-one experience in conducting scientific research that will prepare them to be highly competitive candidates for graduate programs, and ultimately, for careers in teaching and science.

Memories make us who we are. They serve as repositories of all kinds of information from our daily lives, from mundane details to extravagant theories and personal musings. This information isn’t randomly loaded into a storage unit as happens in a desktop computer. Instead, our memory system structures the incoming information. Researchers have long suspected that memories of the same space might be stored together or linked in some way. Others have suggested the same thing for time, that we might have a special temporal index that organizes what we’ve experienced. Some have proposed that our memory systems include special brain cells, or networks of cells, dedicated to encoding spatial and/or temporal information. Similar questions can be asked concerning how memory evolved in vertebrates and other animals. How did memory come to work the way it does? Did it emerge from a system initially involved in navigating space or tracking the flow of time? Do space and time have the same status in structuring memory or is one more fundamental? Answers to these basic scientific issues will enhance understanding of memory disorders and guide interventions to improve memory and ameliorate memory decline.

The workshop on Memory, Space, and Time will take place in Tucson, Arizona, with a multi-disciplinary group of speakers from philosophy, psychology, and neuroscience, as well as local contributors from the sciences and humanities. Selected graduate student scholars working in related areas will receive travel stipends. This workshop will initiate a collaboration on a volume or journal special issue, to be released in open access form following the conference.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.