Stephen W. Kuffler, founding chair
The department in 1967 (back to front) Ed Furshpan, Steve Kuffler, David Hubel, David Potter, Torsten Wiesel, and Ed Kravitz
The Department of Neurobiology, established in 1966 with Stephen W. Kuffler as Chair, was the first of its kind. The intent was to bring together members of traditional departments-- physiologists, biochemists, and anatomists-- in order to understand the principles governing communication between cells in the nervous system. This interdisciplinary approach was revolutionary at the time, and the interdisciplinary theme has continued to permeate the evolution of the field of neuroscience ever since. The founding faculty and their students posed questions and made discoveries that helped define the field of modern neurobiology. The Department emphasized scholarship and education from the start, and many young scientists who thrived in this atmosphere went on to seed neuroscience programs throughout this country and abroad. The expansion of neuroscience research over the past generation has been astounding. The excitement and advances of modern neurobiology have attracted many superb scientists and some of the very best students in the biological sciences.
Among the major breakthroughs during the early era were: description of receptive field organization in the retina and visual cortex; delineation of neural circuits that underlie visual perception; discovery of critical periods during development when synapses form and are stabilized in the cerebral cortex; electrophysiological analysis of excitatory and inhibitory chemical synaptic transmission, including the phenomenon of presynaptic inhibition; characterization of GABA and other amine neurotransmitters; the first demonstration that peptides play a role in synaptic transmission; discovery of electrical excitation and inhibition, and appreciation of the importance of electrical coupling between neurons during development; characterization of the unique properties of single neurons in simple nervous systems; demonstration that glia in the brain modulate changes in extracellular ion concentrations; maintenance of nerve cells in long-term cultures, and the characterization of neuronal plasticity regarding neurotransmitter synthesis. One of the highlights of this period was the awarding of the Nobel Prize in 1981 to David Hubel and Torsten Wiesel for their work on visual processing.
Kuffler was succeeded as Chair by Torsten Wiesel in 1973, and then by David Potter in 1982. Gerald Fischbach assumed the Chair in 1990, followed by Carla Shatz who served from 2000 to 2007. In 2008, Michael Greenberg became the Neurobiology Department Chair.
The Department has grown to keep pace with the rapid expansion and diversification of neuroscience research. At the present time, faculty research interests range from the molecular basis of neurite outgrowth to mechanisms of visual perception and behavior. The faculty, currently numbering 30, will continue to grow as we expect to make one or two new appointments each year over the next five years.
Faculty in the Department emphasize one and often more of the following areas of research: molecular neuroscience, including mechanisms of neural development, auditory transduction, regulation of circadian rhythms and biological clocks; ion channel biology, including the assembly, structure/function, pharmacology, and modulation of channel proteins; synaptic biology, including molecular analysis of transmitter release and transmitter/receptor interactions, biophysics and mathematics of synaptic transmission, properties of neuronal circuits, and changes in synaptic efficacy known collectively as synaptic plasticity; developmental neuroscience, including specification of neuronal and glial cell fates, mechanisms of neuronal survival and death, formation and plasticity of neural connections; systems and cognitive neuroscience, with an emphasis on vision, olfaction, memory, and circadian rhythms.
The Department has remained true to its interdisciplinary ideal, with the current mixture of disciplines quite different from that embraced in 1966. Recombinant DNA techniques have revolutionized the study of brain chemistry. Small regions of the brain can now be analyzed with powerful amplification, differential display and gene chip techniques. The chemical diversity within the nervous system, therefore, can be approached with high sensitivity and high resolution. New chemical labeling techniques have been used to probe the relation between ion channel structure, channel gating, and ion permeation. Patch clamp microelectrodes, sensitive enough to record millionths of a microampere, can detect the movement of ions through single transmembrane channels--the molecular switches that underlie all electrical activity in the brain. As a result, new mechanisms of synaptic transmission and of neuronal integration have emerged. Finely engineered extracellular multi-electrode arrays are being used to analyze patterns of impulse activity in small ensembles of neurons while the animals are alert and performing a trained behavior. Neural activity is also being recorded with optical methods, allowing the simultaneous detection of activity in large populations of neurons. Powerful microprocessors permit the application of more sophisticated stimulus presentations and data analyses in real time. With the addition of the new Brain Imaging Center in 2001, noninvasive imaging such as MRI has been added to the methods used to understand the functional organization of the brain. The pace of discovery has quickened in systems neuroscience, and questions can now be asked about the relation between neural activity and mental events in a more meaningful way.
The academic environment in the Department is enhanced by two weekly seminar series. A formal seminar series is devoted primarily to distinguished speakers from outside the Department, usually outside the University. The other, more informal series is devoted to presentations by predoctoral students and postdoctoral fellows. Additional special events include the Brooks Lecture, which brings a neuroscientist from abroad to the Department for a period of 3 to4 days, and the Kuffler lecture in honor of the founding Chair of the Department. An annual, day-long symposium named for Edward R. and Anne G. Lefler is focused on neurodegenerative disorders. The Department also holds an annual retreat at which faculty present their most recent research results. A variety of journal clubs exist, depending on current interests. Groups that meet weekly to discuss the literature of synaptic physiology, developmental neurobiology, and vision are currently in operation.
The Department emphasizes fundamental research, but much of our work has a direct bearing on diseases of the central and peripheral nervous systems. We now have a greater appreciation for how neurotransmitters and ion channels contribute to the actions of medicines that alter mood, motivation, and cognition. This knowledge holds the promise for more effective and safer drugs. The benefits for the treatment of depression, anxiety, addiction, and memory disorders will be realized in the near future. We also have a much clearer view of how nerve cells die during development, how they degenerate in the mature brain following stroke or trauma, and how they fail during normal and pathological aging. Alzheimer's disease, other forms of dementia, and other types of chronic neural degeneration fall into the latter category. A few examples from our recent studies must suffice:
The mechanism of the action of known trophic factors has been elucidated and a new family of trophic factors has been discovered. They have important roles in the birth of neurons and glia, and in their survival and differentiation. Studies of ß amyloid protein and other proteins that co-aggregate with it have a direct bearing on Alzheimer's disease. An important insight about the cause of Charcot Marie Tooth Disease, the most common form of inherited peripheral neuropathy, was obtained from basic experiments on gap junction proteins (connexins). Molecular and biophysical characterization of hair-cell adaptation in the cochlea led to the isolation of an unusual myosin, which is the culprit in Usher's Syndrome, the most common form of congenital deafness and blindness. An important hypothesis regarding dyslexia has been formulated, based on measurements of the rate of information flow from the retina to the visual cortex. Discoveries of the mechanisms and molecules associated with brain wiring during development will help formulate treatments for children with learning disorders. Knowledge of the molecular control of circadian rhythms will lead to therapies for the treatment of sleep disorders.
The Department at the Quadrangle occupies about 60,000 square feet in the Isabelle and Leonard Goldenson Building and in the contiguous Warren Alpert Building. The Goldenson Building, named for the family who donated funds toward its realization, was dedicated October 3, 1994. The inscription etched in the marble on the building's entrance reads "To explore the universe of the brain for the benefit of people everywhere".
In addition to the research labs, the Department contains superb common facilities, including seminar/conference rooms, a neuroscience library, a machine shop, equipment rooms, confocal microscopy, and an electron microscopy facility (shared with the Department of Cell Biology). A new Brain Imaging Center in the Goldenson Building, equipped with a 4.7T magnet for MRI studies, is operated in collaboration with the Brigham and Women's Hospital, and an expanded confocal microscopy facility equipped with two-photon and deconvolution microscopes is operated in collaboration with the Harvard Center for Neurodegeneration and Repair.