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Cortical control over area-specific thalamic input

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PROJECT SUMMARY/ABSTRACT Sensory thalamic nuclei relay information from sensory surfaces such as the retina and the vibrissae on rodent's face to the cerebral cortex, connecting the cortex with the outside world. In turn primary sensory areas of neocortex project to sequentially connected higher order neocortical areas that mediate such functions as perception, memory and movement control. Knowing the mechanisms that direct thalamocortical axons to the correct neocortical target is therefore important for understanding the development of brain function, and aspects of abnormal development underlying human brain disorders. Although an abundance of studies has uncovered many cellular and molecular signals that control the growth of thalamic axons through subcortical structures, as well as how axons are precisely sorted along their route, little attention has been paid to guidance signals inside the cortex itself. Yet substantial evidence indicates that intra-cortical cues exist. The proposed work will utilize a mouse line in which axons from sensory thalamic nuclei have been genetically labeled with fluorescence. This creates a visible map of sensory areas on the surface of the brain. The neocortical area map will be altered in these mice by manipulating the neocortical morphogen Fibroblast Growth Factor 8 (FGF8), which will shift and duplicate sensory areas. Axonal tracers will be placed in different parts of the altered area map, using the fluorescent map to identify the desired targets. After the tracer has had time to travel from cortex to thalamus, the brain will be fixed and sectioned. The trajectories of labeled thalamocortical axons will be viewed and reconstructed in 3D using a confocal microscope. These trajectories will shift dramatically at points of normal thalamic guidance in the cortex because the cortical map itself has been disrupted. The study will test the hypothesis that positional cues for thalamic axons are present in the cortical subplate and in layer 4, the major recipient of thalamic input, and will be a preface to investigating the molecular identity of such cues.

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