The 2002-2003 M.R. Bauer Foundation
Colloquium Series, Distinguished Lecturer Series and Scientific Retreat

Introduction

I am pleased to present this year's proceedings of the M.R. Bauer Foundation Colloquium Series, Scientific Retreat, and Distinguished Guest Lecturer Series at Brandeis University's Volen National Center for Complex Systems. The generous support of the M.R. Bauer Foundation for these programs is now in its ninth year, and it has enabled the Volen Center to bring neuroscientists carrying out some of the most interesting work in the field to campus. The lectures and informal interactions that took place in the last year facilitated contacts among Brandeis's faculty and students with leading practitioners from the United States, Britain, Canada, Israel, and Switzerland-reflecting the international community of neuroscientists. The following proceedings describe, I believe, the excitement created by many of the new investigations in key areas of neuroscience. My colleagues at the Volen National Center join me in conveying our sincere thanks to the M.R. Bauer Foundation for its uninterrupted support, which has made these visits possible.

The M.R. Bauer Colloquium Series hosted seven speakers in 2002-03. Many of the talks focused on movement, spatial orientation, and decision-making. Michael Graziano, Ph.D., from Princeton University's Department of Psychology proposed that the motor cortex does not contain a map of the muscles, as had been previously believed, but rather a "map" of the space towards which movements are directed. He has found that different regions in the brain, especially the primary motor and premotor cortex, control different types of actions in different spatial regions. Paul Glimcher, Ph.D., from New York University's Center for Neural Science, reviewed recent findings on the computational architecture for decision-making, and suggested that a mathematical framework based in current economic theory offers the "critical computational tool" for understanding the neural basis of human and animal decision-making. Using robotic modeling, Arthur Prochazka, M.D., a member of the University of Alberta's Division of Neuroscience, addressed one of the big unresolved questions in motor control physiology-do simple reflex pathways, such as the pathway underlying the tendon jerk, make a significant contribution to the control of movement? His answer is that reflexes can rescue a collapsing gait pattern, if the underlying activity is weak, but they are not likely to do more than change the body's attitude during movement—for example, in stretching to tip-toe—if the underlying activity is strong. Efforts to understand the neurobiology of movement bring together work that spans molecules to behavior. That important theme was taken up by the two Bauer Distinguished Guest Lecturers: Rüdiger Wehner, Ph.D., and Michael Bate, Ph.D., as described below.

Other speakers in the Colloquium Series addressed the most recent important findings on synaptic plasticity, or the brain's ability to reshape and rewire itself, for learning and memory. Neal Waxham, Ph.D., from the University of Texas Medical School's Department of Neurobiology and Anatomy, used three-dimensional structural analysis and live cell imaging to investigate the role of a key enzyme, CaM-kinase 11, in synaptic plasticity. He is seeking to pinpoint the temporal and spatial changes that occur when this enzyme is locked into the synapse, as new information is stored. Catherine Dulac, Ph.D., from Harvard University's Department of Molecular and Cellular Biology, described her work on pheromone detection, linking genes with behavior. Pheromones, which are detected by a structure in the nose called the vomeronasal organ, signal the sex and dominance of animals. Dulac estimated that the receptor gene families contain as many as 400 to 500 pheromone receptors, which are divided into distinct subgroups, far exceeding earlier estimates. Her work suggests that pheromone detection involves a remarkable molecular and cellular complexity. Haim Sompolinsky, Ph.D., from the Racah Institute of Physics at the Hebrew University of Jerusalem, spoke about the balance that neural networks in the cortex achieve between excitation and inhibition. Using statistical physics to look at the way in which network architecture, neural dynamics, and computation interact, Sompolinsky examined the cooperative aspects of information processing in the brain.

Now in its fifth year, the M.R. Bauer Distinguished Guest Lecturer Series brought two outstanding scientists to campus in 2002-03. Rüdiger Wehner, Ph.D., is professor and chair of the Department of Zoology and director of the Institute of Zoology at the University of Zürich in Switzerland. In his major work on ants, Wehner is trying to answer a general question: How can a tiny brain weighing about one-tenth of a milligram solve complex computational tasks such as navigating in a featureless desert? Wehner discovered that special photoreceptor cells along the top of the ant's eye are tuned to the polarized ultraviolet light of the sun. The pattern of polarized sunlight changes in color and geometry throughout the day as the sun changes position, giving the ants a "map" by which they can navigate. Furthermore, Wehner found that only three neurons integrate information from the photoreceptor cells, and these neurons do not react to light intensity, only to the vector orientation of light. Each point of the compass is defined for the ant by a particular response ratio of the three neurons (analogous to the human response to the three basic colors). Therefore, the neural network underlying the ant's navigation system may be similar to the human neural network for color. The study of the ant's navigation system shows that its brain is organized in modules or systems, a principle that has been conserved by evolution in creatures ranging from ants to humans. Neuroscientists refer to the notion of "modularity" when they talk about how the brain is organized into 5 distinct but interacting systems. In the case of ants, "modularity" is seen in high-level tasks that can be accomplished by lower-level solutions built into separate parts or modules of the brain.

The year's second M. R. Bauer Distinguished Guest Lecturer was Michael Bate, Ph.D., the Royal Society Professor of Developmental Neurobiology at the University of Cambridge in England. Bate's work focuses on the neuromuscular juncture during early development. He is especially concerned with the way in which the machinery underlying coordinated movement is assembled in the embryo. In part, this interest involves understanding how neuron motor circuits are generated and then begin to function. In the earliest developmental stages, how do nerve cells know how to make the right connections with the appropriate muscles? One of the important findings of Bate's work is that the motor system in the fruit fly is constructed without the need for sensory input. Bate also addresses how the cells of the motorneuron system are organized. The dendrites of these cells, or the branches of neurons that receive synaptic inputs in the central nervous system, are organized in a highly predictable spatial array that corresponds to the pattern of muscles on the periphery. Scientists call this a "myotopic map," which suggests evidence of an active process that causes dendrites of nerve cells to grow into or target specialized areas during early development. Again, through a series of experiments, Bate shows that the map forms even without input from muscles. It therefore appears to be an autonomous property of motorneurons and has nothing to do with the periphery. This evidence provides just fragmentary glimpses of the way that the motor system is built, but these insights allow us to make a reasonable estimate of the process for the first time.

The 2003 Volen Center Retreat, sponsored by the M.R. Bauer Foundation, examined "Interesting Systems." For the first time, the Retreat, which took place on March 3, 2003, was held at the New England Aquarium in Boston. Eve Marder, Ph.D., the Victor and Gwendolyn Beinfield Professor of Neuroscience at Brandeis, took up a question later addressed by Sompolinsky in the Colloquium Series—how the stability of complex neural circuits is maintained during developmental growth. Her work, based on experimental and computational approaches, is designed to explain how cellular and circuit homeostasis occurs in the presence of cellular plasticity. Using experimental results from the crustacean stomatogastric nervous system, Marder demonstrated that the long-term maintenance of stable neural circuit behavior requires the coordinated tuning of both intrinsic membrane properties (the number and kind of ion channels that provide electrical excitability) and inhibitory synapses (the connections between neurons involved in cellular plasticity). Tim Hickey, Ph.D., professor of computer science at Brandeis, presented a new approach to studying nonlinear systems. By using interval arithmetic constraints, he is seeking to make "provably correct" inferences about the parameters of complex mathematical systems. Hickey is currently testing the technique on hybrid systems in which a digital controller interacts with the physical environment. Complex neural assemblies may offer, in Hickey's words, interesting non-linear case studies for the solver. Robert Malenka, Ph.D., from Stanford University's Department of Psychiatry and Behavioral Sciences, provided an overview of synaptic plasticity, which he defined as the ability of experience to modify the organization and behavior of neural circuits in the brain. Malenka described synaptic plasticity as a complex system, in which its two best understood forms, long-term potentiation (a long-lasting strengthening of a synapse) and long- term depression (a corresponding weakening of a synapse), are caused by different patterns of neural activity. He suggested that synaptic plasticity might also play an important role in the development of pathological behaviors, such as addiction. Michael Kahana, Ph.D., associate professor of psychology at Brandeis, described experiments in spatial navigational memory he conducted with epileptic patients who were undergoing invasive monitoring to identify seizure points in the brain for surgery. By playing a game in which the patients explored a virtual space, Kahana recorded from single neurons in various parts of the brain in order to show that the hippocampus is specialized for spatial position while the parahippocampus is specialized for spatial views. Kahana's work fits especially well with the research of Graziano and Wehner, who have demonstrated the modularity of the brain in spatial navigation. Xiao-Jing Wang, Ph.D., associate professor of physics at Brandeis, spoke about modeling studies he has conducted on the mechanisms of working memory and decision making. A major challenge for neuroscientists has been to understand the cellular and synaptic mechanisms of the circuits in the cortex of the brain. In order to maintain working memory, the brain has to convert a transient pulse-like impulse into an ongoing activity that can be self-sustained over a much longer time. Wang's computer modeling of this process shows a "slow reverberation" characteristic of the neural circuits that create human cognition.

Over the past nine years, the M. R. Bauer Foundation Colloquium and Scientific Retreat have helped to promote the exchange of ideas and new methodologies, and, in general, to advance the study of neuroscience. In the past five years, the M.R. Bauer Distinguished Guest Lecturer Series has brought some of the most accomplished neuroscientists in the world to the University. Both programs have created a strong sense of community among Brandeis's scientists and the visitors from other institutions. Our faculty and students have benefited tremendously from their interactions with the Bauer Colloquium speakers and Distinguished Guest Lecturers, and these visitors in turn have taken away a strong sense of the exciting research and learning at the Volen Center. This booklet represents an important part of the Volen Center's effort to reach out to neuroscientists in the broader community in order to make this work more widely known and continue to facilitate scientific collaboration and discussions. It is with great pleasure that I recognize the support of the M.R. Bauer Foundation for making these activities possible through its foresight and generosity.

Arthur Wingfield, D.Phil.
Nancy Lurie Marks Professor of Neuroscience and
Director, Volen National Center for Complex Systems