It is generally assumed that the generation of neurons ceases before or soon after birth, and consequently, that neurons are not replaced in the brain of adult animals. According to this view, neurons are long-lived, such that their synaptic connections are able to encode information over long periods of time. Acquisition of information in learning and memory is thought to rely on the strengthening and weakening of pre-existing synaptic connections. In the last several years, however, this traditional view has been challenged by increasing numbers of reports of adult neurogenesis in the brains of birds, fish, mice, rats, and primates, including humans. Furthermore, newly generated neurons have been observed to functionally integrate into existing neuronal circuits in adult animals. I am interested in manipulating the birth, death, and function of newly generated neurons by genetic methods in the adult animal to gain a better understanding of their concerted roles in memory storage. These experiments will allow us to probe the mechanisms and behavioral consequences of adult neurogenesis and its role in plasticity of the adult brain. For instance, why do adult animals require the addition of neurons to their brains? Do neurons acquired in adult life participate in a special form of memory storage that requires the replacement of old neurons? How do adult-generated neurons integrate in a functioning brain circuit?
-Neurogenesis in the brain of songbirds
The most robust demonstration
of neurogenesis in the adult brain has been characterized in songbirds. In
many species of songbirds, the capacity to learn song varies during adult
life, and this variation is correlated to radical neuroanatomical changes
in brain nuclei controlling song, which include variations in neuronal size
and number. For instance, adult male canaries develop new songs seasonally.
In the winter before the spring breeding season, they develop a new song pattern
and add neurons to song control regions in the brain. During the summer, neurons
are discarded from these areas, song patterns degrade, and neuronal production
decreases. These observations have led to the hypothesis that song learning
in birds may involve irreversible changes in the molecular properties of the
relevant neurons, analogous to the terminal differentiation of some cell types.
According to this hypothesis, neurons that encode the memory traces for a
particular song cannot be used again to encode a different song; in other
words, song-related neurons are for single-use, or disposable. To address
these questions and others concerning the function of the newly generated
neurons in the brains of adult songbirds, I plan to apply the techniques of
molecular genetics to mark and manipulate the birth, death, and function of
adult-born neurons in the song-control centers of the adult songbird brain.
Selected Publications:
Lois, C. & Alvarez-Buylla, A. (1993) Proliferating subventricular zone cells in the adult mammalian brain. Proc. Natl. Acad. Sci. USA. 90, 2074-2077
Lois, C. & Alvarez-Buylla, A. (1994) Long-distance migration in the adult mammalian brain. Science 264, 1145-1148
Alvarez-Buylla, A. & Lois, C. (1995) Neuronal stem cells in the brain of adult vertebrates. Stem Cells 13:263-72.
Lois, C., Garcia-Verdugo, J-M., & Alvarez-Buylla, A (1996) Chain migration of neuronal precursors through glial tubes in the brain of adult rodents: a novel form of migration in the CNS. Science 271: 978-981.
Lois, C., Refaeli, Y., Qin, X.F., Van Parijs, L. (2001) Retroviruses as tools to study the immune system.Curr Opin Immunol. 13: 496-504.
Lois, C., Hong, E.J.,
Pease, S.S., Brown, E.J. and Baltimore, D. (2002) Germline transmission and
tissue-specific expression of transgenes delivered by lentiviral vectors.
Science 295:868
Assistant Professor of Neuroscience, Department of Brain and Cognitive Sciences
Carlos Lois received his
M.D. from the University of Valencia Medical School (Spain). He received his
Ph.D. in cellular neurobiology from the Rockefeller University. After a postdoctoral
fellowship at the California Institute of technology, he joined the Department
of Brain and Cognitive Sciences and the Picower center for Learning and Memory
in 2002. He holds the Poitras career Development Professorship at MIT.
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