Experiments are proposed to determine why thalampcortical axons do not respond to injury in a way that leads to regeneration of connections and return of cortical function. Four hypotheses will be tested in the somatic sensory thalamus and cortex of the BALB/c mouse to find an explanation for this inability to grow and reform these important connections. One possible explanation is that the thalamic neurons are unable to mount an axonal growth response because they die after a cortical lesion. A second hypothesis is that extrathalamic axons may out-compete the regeneration of the thalamic fibers, perhaps by preempting available synaptic space. Third, the thalamic axons may start to grow, but not find the substrate molecules in the immediate area to use for guidance. Finally, after the thalamic axons mature they may permanently lose the capacity to elongate and form new synapses. Thalamic fiber growth will be studied using a transplantation paradigm in which embryonic cortex is placed in a corresponding region of an adult brain. The design for the first three sets of experiments involves changing the age of the donor tissue at the time it is placed in an adult host, while the last experiment requires that the host age be progressively reduced from adult to newborn. The analyses are focused on labeling the thalamic axons for examination in the light and electorn microscope and then correlating the axon distribution with the location of immunocytochemically localized cell surface and matrix molecules in the transplants. These results may potentially lead to improved clinical techniques for restoring neural circuitry following injury to the brain and spinal cord.
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