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Mechanisms &Substrates of Somatosensory Plasticity

$198,450R01FY2002HDNIH

University Of Toledo Health Sci Campus, Toledo OH

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Abstract

DESCRIPTION: (provided by applicant) Each year millions of Americans suffer from tactile and related sensory dysfunctions that result from injuries and diseases of the peripheral nervous system. These dysfunctions are difficult to rehabilitate, largely because the underlying central changes are poorly understood and, thus, not open to therapeutic control. Unmasking -- i.e., rapid expression of central connections that normally remain functionally hidden --contributes to initial changes; however, the mechanisms and substrates for unmasking are conjectural. The aim of this research is to evaluate how synaptic inhibition mechanisms, and local, ascending, and descending somatosensory substrates, contributes to subcortical and cortical unmasking of tactile inputs after hand injuries. Neurophysiological mapping, transganglionic labeling of sensory afferents, and pharmacological and surgical blockades of specific brainstem and cortical substrates will be used to test four hypotheses about how unmasking occurs in the cuneate nucleus in the brainstem, and in area 3b somatosensory cortex. This work re-examines major tenets of current plasticity theories from the standpoint of unmasking; in addition, it explores a novel view that inhibition mechanisms may provide cortex with initial protection from abnormal inputs that result from subcortical unmasking. This view is provocative in suggesting that the brain has normal protective mechanisms that might be used therapeutically to control cortical changes that underlie sensory dysfunctions. The long-term objective of the research is to identify subcortical and cortical mechanisms that cause tactile and related sensory dysfunctions after nerve or root injury, limb amputation, and peripheral neuropathies, with the idea that these mechanisms may be exploited as rehabilitative intervention points.

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