The long range goal of work described in this proposal is the correction of handicaps, as found in Alzheimer's, Parkinson's and stroke patients, that result from the selective and partial loss of brain cells. It is suggested that a possible solution to these handicaps is to tap the brain's own potential for neuronal replacement. This potential is widely expressed in oscine songbirds, such as the canary and zebra finch. The work described here uses their song system, which is necessary for the acquisition and production of learned song. We will study the factors that regulate neuronal replacement in this system, including the role of experience, learning, hormones and trophic factors. An advantage of this system is that it allows us to test for possible relations between neuronal replacement and the acquisition and production of a learned behavior. Specific hypotheses that we will test are: 1) that experience affects the survival of new cells; 2) that experience affects the place of insertion of new cells; 3) that acquisition of long-term memory alters gene expression in a long-lasting, possibly irreversible manner, as occurs during tissue differentiation. Behavioral, anatomical, cellular and molecular tools will be used to test these hypotheses. Understanding the processes of neuronal turnover in adult songbirds may suggest approaches for making this happen, under controlled conditions, in the human brain when this seems clinically desirable.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH018343-30
Application #
6052794
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (06))
Project Start
1976-12-01
Project End
2004-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
30
Fiscal Year
2000
Total Cost
$367,195
Indirect Cost
Name
Rockefeller University
Department
Veterinary Sciences
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Nottebohm, F (1996) The King Solomon Lectures in Neuroethology. A white canary on Mount Acropolis. J Comp Physiol A 179:149-56
Kirn, J; O'Loughlin, B; Kasparian, S et al. (1994) Cell death and neuronal recruitment in the high vocal center of adult male canaries are temporally related to changes in song. Proc Natl Acad Sci U S A 91:7844-8
Nottebohm, F; O'Loughlin, B; Gould, K et al. (1994) The life span of new neurons in a song control nucleus of the adult canary brain depends on time of year when these cells are born. Proc Natl Acad Sci U S A 91:7849-53
Rasika, S; Nottebohm, F; Alvarez-Buylla, A (1994) Testosterone increases the recruitment and/or survival of new high vocal center neurons in adult female canaries. Proc Natl Acad Sci U S A 91:7854-8
Kirn, J R; Nottebohm, F (1993) Direct evidence for loss and replacement of projection neurons in adult canary brain. J Neurosci 13:1654-63
Schwabl, H (1993) Yolk is a source of maternal testosterone for developing birds. Proc Natl Acad Sci U S A 90:11446-50
Alvarez-Buylla, A; Ling, C Y; Nottebohm, F (1992) High vocal center growth and its relation to neurogenesis, neuronal replacement and song acquisition in juvenile canaries. J Neurobiol 23:396-406
Kirn, J R; Alvarez-Buylla, A; Nottebohm, F (1991) Production and survival of projection neurons in a forebrain vocal center of adult male canaries. J Neurosci 11:1756-62
Alvarez-Buylla, A; Theelen, M; Nottebohm, F (1990) Proliferation ""hot spots"" in adult avian ventricular zone reveal radial cell division. Neuron 5:101-9
Alvarez-Buylla, A; Kirn, J R; Nottebohm, F (1990) Birth of projection neurons in adult avian brain may be related to perceptual or motor learning. Science 249:1444-6

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