The long term objectives of this proposal are to understand the cellular mechanisms that underlie the capacity of the cerebral cortex to adapt to changes in patterns of input from the peripheral sense organs in adults. These mechanisms not only underlie the capacity of the cortex to make perceptive judgments about the external world but appear also to be fundamentally involved in the learning of skills and in relearning them after stroke and other forms of brain injury, as well as in the aberrant perceptions that accompany central and peripheral lesions of sensory pathways. The proposed studies to be carried out in adult macaque monkeys, involve four sets of experiments. All deal with the role of activity dependent changes in cells and their axonal distribution patterns at subcortical and cortical levels of the somatosensory pathways in influencing the representation of the body surface in the somatosensory cortex and seek to determine the relative contributions of these changes to representational plasticity occurring after lesions of peripheral nerves or of spinal cord pathways. The first set of experiments deals with the issue of whether central and peripheral forms of deafferentation result in the same or in fundamentally different transsynaptic changes in the brainstem and thalamus. The second set of experiments deals with the extent to which the two forms of deafferentation lead to withdrawal from the thalamus and from the cerebral cortex of axon terminations of cells subjected to transsynaptic changes, as a mechanism promoting expansion of representations with intact peripheral innervation. The third set of experiments deals with the influence of the two forms of deafferentation on two fundamentally different sets of cells in the thalamus that appear to be engaged in different aspects of thalamocortical integration. The fourth set of experiments deals with the capacity of central and peripheral forms of deafferentation to evoke increased gene expression of growth factors and their receptors, and with the possibility that withdrawal of axons of deprived cells may be accompanied with sprouting of axon terminations of cells with intact innervation in the thalamus and cerebral cortex. The methods to be used are a combination of physiological localization and anatomical tracing of the axons of individual nerve cells, coupled with immunocytochemistry to define cells populations and in situ hybridization histochemistry to define levels of mRNA expression.
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