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.
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