Links to People doing exciting brain research.
Places where exciting work is being done.
1) the molecular neuroscience of brain development, synaptic contact establishment and regulation, etc, {people like- Eric Kandel, Mary B. Kennedy, Susumu Tonegawa , Gina Turrigiano, John Lisman, Daniel Johnston, Paul T. Kelly, Tim Tully, R. Lathe, William T. Greenough, William G. Quinn, Kai Zinn, and Erin Schuman.}and
2) the computational neuroscience that is typically built on electrophysiology {people like-Christof Koch, David I. Perrett, J. Anthony Movshon, Terrence Sejnowski }, and
3) theoretical biology and the new science of complexity {people like- Stuart Kauffman, Francis Crick }.
I think the closest to what I am interested in is the approach taken
by folks like Gerald Edelman.
Work being done by people like James
C. Houk and Andrew G. Barto is also on the right
track. There is a whole new generation of researchers who are trying to
push the envelop of applying results from molecular and cellular neurobiology
to complex neural network models. For example, Xiao-Jing
Wang. I think we can get a lot of good use out of the World Wide Web
in the future as a means of allowing communication between people who are
interested in all aspects of minds, biological brains, and artificial brains.
Click here to go back to the top of this page.
Eric Kandel
How
Scientists win friends: In the last decade of the 20th century, it
is not in the arts that we find the most innovative or imaginative work
taking place, observed Dr. Eric Kandel at Psychiatric Institute's Annual
Scientific Conference at Arden House in November, but in the sciences,
particularly in neurobiology. Dr. Kandel, Director of the Howard Hughes
Medical Institute, was the after-dinner speaker at the conference and he
once again dazzled the audience with his approach to what he called "the
central unsolved issue in biology: the problem of the mind." Describing
two forms of learning, the explicit and the implicit, he explained some
of the brain mechanisms which transform short-term memory into long-term
memory. Elegant reasoning and an imaginative leap into the future brought
him to predict a "little red pill" which will enhance memory.
The real revolution in the field of psychiatry, he stressed, is the merger
between cognitive psychology and neuroscience which is invigorating scientists
to explore cognition and emotion from the point of view of molecular biology,
as exemplified by his laboratories.
New
NIMH Center
The National Institute of Mental Health awarded Columbia University
a five-year, approximately $6 million grant last fall to establish a Center
for Neuroscience Research. Headed by Dr. Eric Kandel, University Professor
and Howard Hughes Medical Institute senior investigator, the center is
focused around the following two questions: What molecular mechanisms contribute
to learning? Do learning and development share common strategies and genes?
Capitalizing on Columbia's strength in basic science, particularly in transgenic
biology, in the developmental biology of the nervous system, in the molecular
biology of signal transduction, and in the neurobiology of synaptic plasticity
and behavior, the new center hopes to create a bridge between molecular
biology and higher mental processes such as learning and memory.
Genetic approaches, including transgenic animals and gene transfer methodology,
will be key to the study of how individual genes control development, behavior,
and learning in mammals. Center researchers will study how changes produced
by individual genes are reflected in behavior by examining neuronal circuitry,
the circuitry's signaling and plastic capabilities, and the circuitry's
ability to be modified by experience.
The Center faculty consists of Eric Kandel, director; Richard Axel, co-director;
Thomas Jessell; Argiris Efstratiadis; Franklin Costantini; Steven Siegelbaum;
Jane Dodd; Craig Bailey; and Robert Hawkins.
CaMKII Regulates
the FrequencyResponse Function of Hippocampal Synapses for the Production
of Both LTD and LTP
Mark Mayford,* Jian Wang,* Eric R. Kandel,* and Thomas J. O'Dell *Howard
Hughes Medical Institute Center for Neurobiology and Behavior College of
Physicians and Surgeons of Columbia University New York, New York 10032
Department of Physiology University of California, Los Angeles School of
Medicine Los Angeles, California 90024
Summary To investigate the function of the autophosphorylated form
of CaMKII in synaptic plasticity, we generated transgenic mice that express
a kinase that is Ca independent as a result of a point mutation of Thr-286
to aspartate, which mimics autophosphorylation. Mice expressing the mutant
form of the kinase show an increased level of Ca-independent CaMKII activity
similar to that seen following LTP. The mice nevertheless exhibit normal
LTP in response to stimulation at 100 Hz. However, at lower frequencies,
in the range of 110 Hz, there is a systematic shift in the size and
direction of the resulting synaptic change in the transgenic animals that
favors LTD. The regulation of this frequencyresponse function by Ca-independent
CaMKII activity seems to account for two previously unexplained synaptic
phenomena, the relative loss of LTD in adult animals compared with juveniles
and the enhanced capability for depression of facilitated synapses.
Andrew G. Barto. "My research interests center on machine and biological learning. I have been trying to develop learning algorithms that are useful for engineering applications while also making contact with learning as studied by experimental psychologists and neuroscientists. I am interested in artificial and real neural networks, and over the last several years I have focused on connections between reinforcement learning algorithms and dynamic programming solutions to Markov decision problems. Related research is being conducted in collaboration with colleagues specializing in animal motor control. We are working on a model of the cerebellum and other brain regions involved in motor control."
James C. Houk "Growing evidence suggests motor programs may be stored in the cerebellum. Special ion channels and recurrent feedback loops between the cerebellum, cerebral cortex, and basal ganglia may provide the mechanisms for the recall and execution of motor programs. We approach these issues from many perspectives with the goal of identifying the underlying cellular mechanisms and synthesizing these discoveries into a comprehensive understanding of movement control."
William T. Greenough. "Bill Greenough's laboratory's primary foci are the mechanisms at the cellular and system level whereby the nervous system stores information. "Information" includes both traditional psychological forms, such as learning and memory, and forms of information that the nervous system may store of which we are not conscious, such as the organizational effects of a hormone or of early sensory experience on the developing nervous system. We use a multifaceted approach to these problems, with dependent variables ranging from behavior, to optical and electron microscopic measurements, to molecular biology, to electrophysiological approaches."
Tim Tully. "Our research objective is to understand the biological bases of learning and memory formation. We are working on this problem at behavioral, genetic and molecular levels of analysis in the fruit fly Drosophila."
More Drosophila learning by William G. Quinn. "Among the mutants we have isolated, radish has the most interesting behavior. Radish flies show relatively normal learning ability followed by steady memory decay at short and long times after training. Most strikingly, radish, in contrast to other memory mutants, is almost entirely lacking in consolidated (anesthesia-resistant) memory."
Leslie C. Griffith Biochemical Basis of Synaptic Plasticity Drosophila CaM kinases
Christof Koch What are the biophysical mechanisms underlying neuronal computations? Our research foccuses on understanding the circuit properties of small cortical networks with massive feedback (primarily in visual cortex) based on the Canonical Microcircuit concept of Douglas and Martin. In particular, how can supervised or unsupervised network learning algorithms converge to such recurrent networks in a stable manner?
Paul
T. Kelly. Cellular changes contributing to the substrate for learning
can include modifications in the strength of synaptic connections. Long-term
potentiation (LTP) is one example of how synaptic connections can be altered
by prior neuronal activity. It is one of the most widely studied cellular
models of synaptic plasticity. Elucidation of its underlying molecular
mechanisms may offer important insights about processes underlying learning
and memory.
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Mary
B. Kennedy
Molecular Structure and Function of Central Nervous System Synapses
How does your brain store new information; the face of an acquaintance, the license plate of your new car, or the movements required to throw a baseball? Neurons communicate primarily through chemical synapses that transmit signals by releasing transmitters that cause electrical charges in target neurons. Many of these same transmitters also initiate biochemical charges in the signalling machinery of the synapse itself. Such biochemical "plasticity" is fundamental for information processing and storage in the brain. For example, it is now thought that memories are encoded when the signalling strength of appropriate synapses is permanently increased through biochemical mechanisms triggered by the repeated use of the synapse. Neurotransmitters can trigger the activation of several signal transduction pathways. We are studying the molecular organization of sugnal transduction systems in central nervous system synapses. We have found the postsynaptic density, a specialization of the submembranous cytoskeleton seen at postsynaptic sites in the central nervous system, contains signal transduction molecules that may control the sensitivity of the transmitter receptors, the size of receptor clusters, or perhaps the integrity of the adhesion junction that holds persynaptic terminals in place. Employing a combination of microchemical and recombinant DNA techniques, we have determined the structure of several proteins associated with postsynaptic densities. We are presently studying the associations of these proteins with each other and their specific roles in control of synaptic transmission with the ultimate goal of illuminating the function and the biochemical diversity of this specialized organelle.
In a related project, we found that a neuronal calcium/calmodulin-dependent protein kinase (CaM kinase II), which transfers phosphate from ATP to specific proteins, is concentrated in the postsynaptic density and may play an important role in controlling changes in synaptic strength that underlie memory formation in the mammalian hippocampus. This enzyme is activated by phosphorylation of a threonine located near the calmodulin-binding site. We have developed a new technique to correlate changes in phosphorylation of CaM kinase II and other proteins at synapses in situ with changes in neuronal physiology. This technique involves the use of antibodies that bind only to a particular phosphorylated site on a protein to visualize changes in phosphorylation of the protein in cultured neurons and in brain slices. It provides unprecedented spatial resolution of protein phosphorylation in tissues.
Moon, I.-S., Apperson, M.L., and Kennedy, M.B. The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B. Proc. Natl. Acad. Sci. USA, 91, 3954-3958, 1994.
Gina
Turrigiano. "Our long-term goal is to understand how activity
conjointly regulates intrinsic neuronal properties, synaptic strengths,
and neurite outgrowth to encode experience."
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Synaptic
Physiology of the marine snail Aplysia Tom Nolen Department of Biology,
University of Miami
Daniel Johnston. "the cellular and molecular mechanisms of synaptic integration and long-term synaptic plasticity. "
Professor R Lathe. The molecular basis of memory is, at best, poorly understood. We are attempting to use transgenic technology to test theories of brain function. Our principal interest lies in the mammalian hippocampus, a region thought to play a central role in learning and memory.
John Lisman. Molecular basis of memory. We have done theoretical work suggesting that the repository of synaptic memory may be the calcium/calmodulin dependent protein kinase II contained within a synaptic structure called the postsynaptic density. There is now substantial support for this model and we are attempting further tests.
Lisman, J., 1994. The CaM kinase II hypothesis for the storage of synaptic memory. TINS 17: 406-412.
Leslie Ungerleider
Psychologists have long noted that, with practice, people can
learn a complex motor task--such as rapid sequences of finger movements--and
improve their speed and accuracy until they plateau at a certain performance
level. But the performance doesn't transfer to learning other, similar
sequences--such as another piano tune--only to the one that's been practiced.
That's because the brain uses more space, presumably providing more "power" to perform the practiced sequence, according a new study by psychologists Avi Karni, MD, PhD, and Leslie Ungerleider, PhD, of the Laboratory of Neuropsychology at the National Institute of Mental Health and their colleagues at the National Institutes of Health.
Once a week for five weeks, Karni and Ungerleider measured brain activity in the primary motor cortex of six men who performed two different but highly similar finger-tapping sequences at a set pace. Each subject practiced one sequence 10 to 20 minutes each day but performed the other sequence only during the testing sessions.
During these sessions, the researchers measured brain activity using functional magnetic resonance imaging--a scanning technique that measures the amount of blood oxygen in specific brain regions. After five weeks, the researchers found that tapping the practiced sequence activated a larger portion of the motor cortex than tapping the other sequence. The changes remained a year later as did superior performance on the practiced sequence, with no practice in the intervening time, said Unger-leider.
These results indicate that changes occur in the primary motor cortex as a result of learning, she said. But it is not a generalizable kind of learning: It's specific to one sequence of movements. That's why Ungerleider thinks the brain may set up larger-than-normal expert circuits to handle specific, practiced sequences of movements.
The kind of learning this study looked at is procedural learning, or learning that people don't have to consciously recollect, such as driving a car or riding a bike, Ungerleider explained. It is also the type of knowledge that is negatively affected in people with brain disorders, such as in late stages of Alzheimer's disease.
Although researchers are still trying to uncover the basics about how the brain learns and remembers, scientists hope that the basic knowledge will some day have clinical significance for treating such disorders, she said.
Francis Crick Theoretical Neurobiology.
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Control of Genes, Development, and Plasticity by Neural Impulses
June 9 & 10, 1997 Organizer: R. Douglas Fields, Ph.D. National Institutes of Health, NICHD
Bringing together new research on gene regulation by neural impulse activity, with research on synaptic plasticity and intracellular signaling, this conference explores the molecules and mechanisms that coordinate the structure and function of the brain. It is now known that cell adhesion molecules (CAMs), which regulate nervous system development, are also regulated by action potential activity. By controlling cell-cell interactions and activating intracellular signaling pathways, CAMs are now seen as important molecules in controlling the structure of the nervous system according to the pattern of impulses flowing through developing neural circuits. New experimental and theoretical advances are beginning to show how second messengers, kinases, and transcription factors operate as a system to transmit and integrate information contained in action potential activity and control transcription of genes involved in activity-dependent plasticity. Presentations include studies on invertebrate and vertebrate nervous systems in the context of development, LTP, LTD, and memory.
OLDIES but GOODIES
Wednesday, October 2 - Sunday, October 6, 1996
Higher Brain Systems and Memory (Leslie Ungerleider) Brain Plasticity and Development (Mary Beth Hatten) Brain Circuits and Systems of Memory (Ann Graybiel) Basic Processes of Learning and Memory: Putative Mechanisms (Richard F. Thompson) Mechanisms of Synaptic Plasticity - LTP, LTD and other (Per Andersen) Biophysics and Molecular Biology of Synaptic Plasticity and Memory (Eric Kandel) Genetic Approaches to Mechanisms of Memory (Susumu Tonegawa) Computational Models of Neural Plasticity and Memory (Eve Marder)
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Learning & Memory The neurobiology of learning and memory is entering a new interdisciplinary era. Advances in neuropsychology have identified regions of brain tissue that are critical for certain types of function. Electrophysiological techniques have revealed behavioral correlates of neuronal activity. Studies of synaptic plasticity suggest that some mechanisms of memory formation may resemble those of neural development. And molecular approaches have identified genes with patterns of expression that influence behavior. It is clear that future progress depends on interdisciplinary investigations. The current literature of learning and memory is large but fragmented. Until now, there has been no single journal devoted to this area of study and no dominant journal that demands attention by serious workers in the area, regardless of specialty. LEARNING & MEMORY provides a forum for these investigations in the form of research papers, short communications, and review articles.
Neurobiology of Learning and Memory Concerned with neural and behavioral plasticity, including learning and memory and related aspects of neural adaptation, at all levels of analysis from molecular biology through behavior. The journal's research areas include all areas of the neurobiology of learning and memory. Neurobiology of Learning and Memory includes major theoretical, research, and review papers; research reports; brief reports; rapid communications; and notes.
Behavioral & Brain Sciences. Psychology, neuroscience, behavioral biology, cognitive science, artificial intelligence, linguistics and philosophy.
PSYCHE A refereed electronic journal dedicated to supporting the interdisciplinary exploration of the nature of consciousness and its relation to the brain. PSYCHE publishes material relevant to that exploration from the perspectives afforded by the disciplines of cognitive science, philosophy, psychology, physics, neuroscience, and artificial intelligence. Interdisciplinary discussions are particularly encouraged.
The journal Neuron.
A new neuroscience journal online, Neuroscience-Net.
Neural Computation disseminates important, multidisciplinary research results and reviews of research areas in neural computation-a field that attracts psychologists, physicists, computer scientists, neuroscientists, and artificial intelligence investigators, among others. For researchers looking at the twin scientific and engineering challenges of understanding the brain and building computers, it highlights common problems and techniques in modeling the brain, and the design and construction of neurally inspired information processing systems. Timely, short communications, full-length research articles, and reviews focus on important advances and also cover the broad range of inquisition into neural computation.
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Molecular Neuroscience at Caltech Which genes and proteins direct nerve cell growth and specialization? Which underlie neuronal communication? Which allow the brain to learn and remember? Molecular neuroscientists at Caltech want to know which of the molecules and mechanisms involved in synaptic transmission are modified, and how they are modified, during learning and memory. Does learning and memory involve only the modification of existing synapses or also the addition and elimination of synapses?
Adaptive NetWork Laboratory, UMASS/Amherst, co-directed by Prof. Andrew G. Barto and Richard S. Sutton. Using artificial neural network methods for network learning through realistic interaction with dynamic environments and without the help of knowledgeable teachers
Center for Neuroscience Research on Neuronal Populations and Behavior, directed by James C. Houk, Professor and Chair of Physiology and Professor of Biomedical Engineering, Northwestern University Medical School, Chicago, IL
The Sloan Center for Theoretical
Neurobiology, University of California San Francisco.
See links there to other Sloan Centers for Theoretical Neurobiology.
The Beckman Institute for Advanced Science & Technology at the University of Illinois. Biointelligence research, necessarily, ignores traditional disciplinary boundaries. One issue being investigated at the Beckman is how memories are formed and modified. One group at the institute is looking into modifications in neuronal structures as affected by experience. Another group is examining the molecular changes that appear to be essential to memory formation. Yet another group is considering the nervous circuit changes in information processing.
Center for Molecular and Behavioral Neuroscience of Rutgers University. Acenter in which neuroscience is studied at all levels, from the molecular to the behavioral.
University of California, San Francisco, Neuroscience Graduate Program
Beckman Center for Learning and Memory, Cold Spring Harbor Laboratory. "The neuroscience program at CSH has made tremendous strides in gaining greater understanding of the physiological basis for learning and memory."
The Biocomputing Group at Wayne State University. "The objective is to elucidate the fundamental principles of biological information processing in a task oriented context and to employ these principles to design computational systems with more life-like capabilities, including virtual systems residing on a silicon base and molecular computer designs that in the future could be embodied in carbon."
The center for complex systems at Brandeis University. Dedicated to the interdisciplinary study of intelligence from the perspectives of neuroscience, cognitive science, and computer science.
NYU Center for Neural Science. Application of the most modern cellular and molecular techniques is of course critical to the study of neural systems, and in the Center's laboratories these are used hand-in-hand with, and in the service of, higher level analyses of brain function.
INSTITUTE FOR NEURAL COMPUTATION Researchers are addressing the twin scientific and engineering challenges of understanding how humans function at the neural and cognitive levels and solving major technological problems related to neural network implementations.
Columbia University Center for Neuroscience Research.
A typical IBM mainframe about 1970: IBM 360/75 computer with 512 Kilobytes of main storage, 1 Megabyte of low speed memory, two 2303 drums, a bank of 2314 "Direct Access Storage Devices" (DASD) consisting of eight mountable drives with 22 Megabytes per drive, three 2400 tape drives (one 7-track drive and two 9-track drives), two 1403 printers, and a 2540 card reader/punch. Back.
APL (A Programming Language). Early 1970's: York APL was installed on IBM 360s and became the first version of APL ( A Programming Language) available to many users. This particular version of APL was written at York University. APL was a fairly new language, different in design from anything that had existed before. Late 1970's: VS/APL running on Virtual Machine/Conversational Monitor System (VM/CMS) and IBM 370/145 computers. By 1986 APL was even running on the Apple Macintosh. Back.
Nobel Prize Chemistry 1978 Peter D. Mitchell
(Great Britain, 29.9.1920 - +1992) Great Britain, Glynn Research Laboratories,
Bodmin, "for his contribution to the understanding of biological energy
transfer through the formulation of the chemiosmotic theory"
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1992 Edwin
Krebs, M.D., HHMI senior investigator emeritus at the University of
Washington, shares the Nobel Prize in Physiology and Medicine for discovering
(in the 1950s) protein phosphorylation, a regulatory mechanism in most
living cells.
"Differential activation of mitogen-activated protein kinase in response
to basic fibroblast growth factor in skeletal muscle cells", Campbell,
J.S., Wenderoth, M.P., Hauschka, S.D., and Krebs, E.G., Proc. Natl. Acad.
Sci. USA,92, 870 (1995).
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