Cell death in the avian brain with emphasis on the development and plasticity of the song control system

Programmed cell death is a fundamental feature of brain development, homeostasis, and adult plasticity. One model system, in which the role of cell death in establishment, maintenance and plasticity of neural tissues is evident throughout both early development and in the adult, is the neural circuitry underlying the learning and production of singing behavior in songbirds. The dramatic sexual dimorphism and natural, cyclical growth and regression of the song control system provides a useful environment for studying programmed cell death. Especially valuable and unique to songbirds, the occurrence of cell death in the song control system is correlated to quantifiable changes in a biologically relevant and learned sensorimotor behavior-that is singing. Within this review I explore the topic of cell death in the avian brain primarily within the context of the song circuits. I first establish why songbirds are a useful model for studying cell death and provide a brief overview of the organization of the circuitry underlying song learning and production. I then discuss the processes and mechanisms of cell death during early development and sexual differentiation of the song control system. I present the classic and recent work exploring cell death in the adult avian brain by covering topics of homeostasis and neuronal turnover, seasonal plasticity, and neural injury and insult. Finally, I propose several outstanding questions in the field of cell death biology in the avian brain, which when addressed have great potential to provide unique insight into the role of cell death in the organization and maintenance of neural tissues, the plasticity of developmentally organized neural circuits in the adult, and the mechanisms underlying functional recovery from both natural and injury-induced neurodegeneration.