A study of mechanisms for formation of thalamocortical projectic

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In the development of the brain axons stop growing and form branches upon reaching their targets.The thalamocortical connection is a suitable system for studying this issue, because sensory thalamic axons project primarily to layer 4 of the neocortex, which is well characterized by cytoarchitectonic structure.To date developmental studies have suggested that thalamic axons can recognize the target layer through lamina-specific cues in the cortex, but the molecular mechanism has almost remained unknown.We attempted to reveal characteristics of possible factors that are responsible for layer-specific termination and branching of thalamocortical axons.For that purpose, axonal extension from rat embryonic thalamus on postnatal neocortical slices which had been fixed chemically was used as an experimental model system.Under these conditions the role of membrane-bound components can be analyzed without contamination of soluble factors released from cortical tissues.Thalamic axons extended even on fixed cortex and exhibited farther growth in the deep layers (layers 5 and 6) than the upper layers (layers 1 through 4).Enzymatic treatment to cortical slices prior to culturing further demonstrated that the laminar difference in axonal outgrowth was primarily due to PI-PLC-sensitive components which are present in the upper layers.On the other hand, axonal branching occurred mostly in layer 4 of the fixed cortical slices.This laminar localization of branch formation was slightly weakened in neuraminidase-treated cortical slices with an increase in the number of branches.These findings suggest that GPI- anchored and sialic acid-containing molecules regulate layer-specific thalamic axon growth and branch formation, respectively, through inhibitory activity.