Neurons are normally overproduced and subsequently die in early development. We propose to investigate this overproduction and death in the mammalian retina, midbrain and visual cortex, to determine what factors contribute to a neuron's survival. In a midbrain structure, the superior colliculus, we will manipulate the amount of afference and determine both the range over which synaptic density may vary and the relationship of synaptic density to cell death. In the retain, we will determine if the day a neuron is generated can predict the likelihood and timing of its death, using thymidine autoradiography. For the visual cortex, we will determine if its cellular laminae respond to input and target deletions in the same way other neural structures have been shown to, with the goal of determining how local variations in morphology and cell number are imposed on the general neocortical plan. Finally, we will relate the timing of establishment of connections to and from these structures to the pattern of cell death. In all cases, we will be quantifying the amount of observable cellular degeneration in early brain development consequent to our manipulations. In sum, we propose to investigate the early control of a neuron's survival and also use the information about the patterns of early neuron death to inform us about the mechanisms of the establishment of orderly connections in the developing mammalian brain. This work will have direct relevance for our understanding of the nature of, and the reasons for, reorganization of the human brain following perinatal damage.
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