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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS036469-01
Application #
2039178
Study Section
Sensory Disorders and Language Study Section (CMS)
Program Officer
Baughman, Robert W
Project Start
1997-05-01
Project End
2001-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Florence, S L; Boydston, L A; Hackett, T A et al. (2001) Sensory enrichment after peripheral nerve injury restores cortical, not thalamic, receptive field organization. Eur J Neurosci 13:1755-66
Florence, S L; Hackett, T A; Strata, F (2000) Thalamic and cortical contributions to neural plasticity after limb amputation. J Neurophysiol 83:3154-9
Jain, N; Florence, S L; Qi, H X et al. (2000) Growth of new brainstem connections in adult monkeys with massive sensory loss. Proc Natl Acad Sci U S A 97:5546-50
Florence, S L; Taub, H B; Kaas, J H (1998) Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys. Science 282:1117-21