The Rockefeller University
Hypothesis to be tested: some aspects of functional aging result from reduced replacement in the adult CNS.
New neurons continue to be added to the brain of juvenile and adult vertebrates and this phenomenon has been studied in
considerable detail in the high vocal center (HVC) of male zebra finches (Taeniopygia guttata). It is not clear why some HVC neurons
– but not others - are replaced and what might be the functional benefits of replacement, though it is known that the rate of
replacement diminishes with age. The hypothesis to be tested is that whereas periodic replacement of some neuronal types promotes
a “young” functional profile, failure to replace in older adults restricts learning potential and thus leads to an undesirable aspect of
aging. The P.I. will search for changes in gene statement that occur in replaceable HVC neurons of male zebra finches during or after
episodes of learning or during or after the execution of a learned task, compared to controls in which learning of this task has not
occurred. The same comparisons will be made for survivorship of new neurons. To meet the former of these goals the P.I.’s
laboratory will produce a library of zebra finch brain genes and microarrays that can be used to test selective gene statement in cells
of known age and circuit position. The eventual goal is to understand the mechanisms and benefits of neuronal replacement and to be
able to manipulate this phenomenon and see if it affects the acquisition and maintenance of learned song. The avian material under
study may become a model for brain rejuvenation in general.