The long-term objective of this research is to elucidate the relationship between neuronal structure and function. Experiments proposed here are designed to test our working hypotheses that 1) synaptic activity is required for regressive events as well as neuronal growth during nearly neuron development; and, 2) that dendritic regression in the hippocampal formation is critical for function in the nature animal. The first specific aim is to test the hypothesis that synaptic activity is necessary for the regression of immature features on the dendritic stress of hippocampal granule neurons during early neuron development. The second specific aim is to test the hypothesis that growth in these same neurons also requires synaptic activity. We will test both hypotheses by reducing synaptic activity onto these granule-cells during early development, and then quantifying the regression of immature features on the dendrites, as well as dendritic growth and the appearance of spines. The third specific aim is to test the hypothesis that dendritic regression in hippocampal granule neurons during maturation is critical for adult performance on tasks mediated by this region. To test this hypothesis, dendritic regression in granule neurons will be blocked during late postnatal development. Performance of mature animals in the Morris water maze and on trace eyeblink conditioning, tasks known to be mediated by the hippocampal formation will be assayed. Lack of environmental stimuli reduces synaptic activity, and the effects of such deprivations on the developing hippocampal formation, a region that is critical for learning and memory skills, are not yet known. In addition, the actions of neuroprotective agents, such as N-methyl-D-aspartate receptor antagonists are mediated through a reduction in synaptic activity; such agents are now being used in the clinical setting. Before they are administered to children, it is important that we understand how a reduction in synaptic activity affects early brain development.
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