Neuron production, migration, and differentiation are mostly restricted to early development in warm-blooded vertebrates; however, neurogenesis also persists into adulthood in a broad range of species, among them songbirds, who incorporate new neurons into a brain region (HVC) that controls song production. Increases in spontaneous neuronal replacement in HVC correlate with song changes and with cell death. Therefore, songbirds are an excellent model for studies on functional significance of spontaneous adult neuronal replacement and adult brain repair. Most new HVC neurons become projection neurons in the motor pathway that controls the production of learned song. A second type of HVC neuron is not produced in adulthood. The factors governing the recruitment of one cell type but not the other are not known. In experiments to address this question, we recently demonstrated that targeted photolytic neuronal death of the projection neuron type that normally turns over results in compensatory replacement of the same type. Induced death of the normally not replaced type did not stimulate their replacement. In juveniles, death of the latter type increased recruitment of the replaceable kind. This suggests that neuronal death regulates the recruitment of neurons but only of the replaceable kind. After elimination of replaceable neurons, song deteriorated in some birds; behavioral deficits were transient and followed by variable degrees of recovery, raising the possibility that induced neuronal replacement can restore a learned behavior. In this application we propose to further investigate the relationship between the experimentally induced brain injury, the ensuing brain repair and song behavior. Specifically, we will determine how induced neuronal death causes song deterioration and how subsequent recovery occurs. We will address (1) What variables govern the type and severity of song deterioration and what is the time course of deterioration? (2) Does behavioral recovery depend on the same neural substrates that guide vocal learning during development? (3) Does behavioral recovery after induction of neuronal death depend on neuronal replacement?
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