The long-term objective of my research is to elucidate the relationship between the structure and function of individual neurons int he mammalian cortex. The current application is focused on examining the effects of neuronal activity ont the maturation of neuron structure. Neuronal activity, including sensory input, receptor activation and spontaneous firing patterns, is known to influence synaptic formation and axon maturation in the central nervous system. Very little is known, however, about the effects of neuronal activity on dendritic structure and function. Recently we showed that activation of one form of glutamate receptor, the NMDA receptor, may play a role in dendritic maturation in hippocampal granule neurons. Here we propose to further explore the effects of NMDA receptor activity on the maturation of granule neuron structure and function. The hippocampal formation is known to play a role in certain forms of learning and memory in rodents and humans, and it is important to understand how receptor activation during development affects this region. For example, if our experiments show that there is a critical period for dendritic development, this would suggest that experiences during infancy could have long-lasting effects on the learning capabilities of humans. Similarly, clinical trials of NMDA receptor antagonists are now underway; before such drugs are administered to children, it is important to establish their effects on early brain development.
Specific aim 1 is to test the hypothesis that activation of NMDA receptors affects the maturation of both the dendritic and axonal trees of the granule neurons. Although various forms of neuron activity has been shown to affect he morphologies of both dendrites and axons, the effects of receptor activity ont he dendritic and axonal arbors of the same neuron have not been investigated.
Specific aim 2 is to test the hypothesis that a decrease in NMDA receptor activity during development leads to changes in the electrotonic, or functional, properties of dendritic trees. Only recently has it become possible to assess the electrotonic structure of cortical neurons,a nd the effects of receptor activity on the maturation of electrotonic structure are not known.
Specific aim 3 is to test the hypothesis that there is a critical period for the effects of synaptic activity on dendritic morphology. Critical periods have been documented for the formation of synapses and connectivity patterns in the mammalian cortex, but it is not known if they exist for dendritic maturation.
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