MECHANISMS OF RECOVERY FROM SENSORY DISORDERS
Principal Investigator: SHERRE FLORENCE
Abstract: Topographic order of sensory representations in the brain seem essential for accurate sensory perception, but we know little about how such order is created and maintained. A way of investigating this is to introduce topographic disorder in the primary inputs, and determine the circumstances and mechanisms that recreate order centrally. We have shown in macaque monkeys that nerve cut, repair and regeneration results in profoundly abnormal patterns of peripheral nerve inputs, regardless of the age at which the nerve is cut. However, the peripheral sensory disorders are corrected at higher levels of the somatosensory pathway if the nerve cut and regeneration occurs early in life. Conversely, the peripheral disorders are not corrected after nerve cut in adults. Four studies, using neuroanatomical tracing techniques and multiunit mapping procedures, have been proposed to reveal the mechanism(s) responsible for the central recovery after early nerve cut and generation. The first three will assess whether changes occur that might contribute to correction. Tactual deprivation will be produced by prenatal median nerve cut, repair and regeneration, and after months of sensory experience we will look for evidence of reorganization by assessing (1) receptive field organization int he ventroposterior nucleus of the thalamus, (2) the pattern of thalamocortical projections and (3) the distribution of intrinsic connections of cortical area 3b. The superior recovery after early deprivation indicates that widespread and unrefined connections in the immature somatosensory system allow for integration of synaptic inputs from large regions of the sensory surface. Some of these immature connections may be preserved, and perhaps expanded, after the early injury. The final study will determine whether (4) use-dependent processes underlie the topographic recovery. Much of the research on experience dependent plasticity indicates that inputs activated by the same skin region will produce synaptically coincident patterns of activation, and will reinforce one another in a Hebbian-like fashion. Thus, patterns of activity presumably create topographic order despite peripheral regeneration error. If sensory experience is limited, there should be little or no recovery of topographic order. We will test this in monkeys with prenatal median nerve cut by mapping area 3b soon after regeneration is complete, so that use-dependent processes will have little or no impact on cortical organization. The research findings will have important implications for clinical treatments of peripheral sensory disorders in humans.
Funding Period: 1997-05-01 - 2002-04-30
more information: NIH RePORT