Heads of Laboratories
Fernando Nottebohm, Ph.D.
Dorothea L. Leonhardt Professor
Laboratory of Animal Behavior
Huntington’s disease is a neurodegenerative disorder of late onset. The Nottebohm laboratory has developed transgenic zebra finches that express the human mutant gene that causes the disorder and uses song learning and song production to track the modus operandi of the mutant gene. Dr. Nottebohm is also interested in how our view of ourselves and of the universe came to be.
The Nottebohm laboratory has worked on the neurobiology of vocal learning in songbirds, work that uncovered the circuits for the acquisition and production of learned vocalizations and revealed that some of the song nuclei were sexually dimorphic and changed volume seasonally. A closer inspection of this phenomenon in a particular song nucleus led to the discovery that new neurons were continually produced in adulthood and that survival of the new neurons was affected by use and disuse. These neurons were born by division of radial glia in the ventricular zone of the lateral ventricle and from there migrated through the adult telencephalon to their final destination. In canaries, which learn new songs every year, the production of new neurons was accompanied by the replacement of older neurons of the same kind that had died. This replacement peaked at times of song change. In zebra finches, which learn their song only once, the new neurons born in adulthood did not replace others, but led to a net gain in their numbers; as this happened, song became more stereotyped and resistant to deafening. These findings challenged existing ideas that held that all the plasticity required for learning was vested in the number and status of synapses. In parts of the songbird forebrain not related to song, neurons are replaced in adulthood at times of peak novel stimulation.
Ongoing work in the Nottebohm laboratory, led by senior research associate Wan-Chun Liu, is focused on understanding neurodegenerative disorders. In an effort to understand how Huntington’s disease develops, Dr. Nottebohm and Dr. Liu have inserted into the early embryo of zebra finches the mutant human Huntingtin gene that is responsible for Huntington’s disease. The mutant human gene has 145 CAG repeats and is passed down from one generation to the next. These transgenic birds show difficulty copying the song of an adult model, and once they reach adulthood the song starts to deteriorate. The researchers are interested in understanding whether the difficulties with song learning and the time of onset and extent of song deterioration are related to the number of CAG repeats and, if so, in what manner. Only four CAG repeats normally occur in zebra finches.
Dr. Nottebohm has also turned his attention to a project in which he has had a long-standing interest: the history of key events in human evolution and in the evolution of human culture. He is interested in describing this progression as a biological phenomenon, using the standards of evidence and disbelief normally
applied to science.
Born in Buenos Aires, Dr. Nottebohm earned his undergraduate degree in 1962 and his Ph.D. in 1966 at the University of California, Berkeley. He spent a year at the University of Cambridge as part of his doctoral training before joining Rockefeller in 1967 as assistant professor. He became associate professor in 1971 and professor in 1976.
Dr. Nottebohm’s many awards and honors include The Mortimer D. Sackler, M.D. Prize for Distinguished Achievement in Developmental Psychobiology in 2011, the 2006 Benjamin Franklin Medal in Life Science, the 2005 Karl Spencer Lashley Award of the American Philosophical Society, the 2004 Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Science, the 1999 Ipsen Foundation Prize in Neuronal Plasticity, the 1997 McKnight Foundation Senior Investigator Award in neuroscience and the Charles A. Dana Award for Pioneering Achievement in Health Sciences in 1992. He was elected to the National Academy of Sciences in 1988.
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