This project will characterize the appearance of gap junction coupling in developing visual cortex in ferrets and evaluate its role in the establishment of columnar organization. Local cell assemblies display coherent changes in intracellular [Ca] measured with fura-2 due to gap junction communication. In the first specific aim, Fura-2 imaging as well as injection of low molecular weight dyes that cross gap junctions will be used to characterize the timing of the appearance of these """"""""neuronal domains"""""""" in ferret visual cortex during early development when functional cortical inputs, architecture, and response organization are becoming established. The cortical layers involved and orientation of domains will be characterized, and time lapse measurements of fura will show the dynamics of formation and dissipation of domains. In the second specific aim, the persistence of domains through early cortical development will be followed by studying slices from late embryonic, neonatal, and postnatal animals up to two months old. The third specific aim focuses on the initiation and propagation of domains. High speed video methods will be used to determine the speed of activation of domains, and this, along with whole cell patch recording of electrical activity of cells within domains and pharmacological blockade of sodium spikes, calcium spikes, and transmitter receptors, will be used to determine the mechanisms for propagation of Ca waves between cells. The influence of neurotransmitters on domains will be studied to determine the likely effects of synaptic inputs as they are established. Finally, in the last specific aim, chronic blocking of gap junction coupling using osmotic minipumps to deliver octanol, halothane, and 16-doxyl stearic acid will be used to test the hypothesis that electrical coupling within domains plays a role in the establishment of the functional columnar organization of cortex and its physiological responses to visual stimuli.
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