After damage to afferents from the hand as they course in the dorsal columns of the spinal cord, deprived portions of the brainstem cuneate nucleus, somatosensory thalamus, and somatosensory cortex become unresponsive to tactile stimuli and hand use is impaired. However, within 1 - 2 months, cortex can be reactivated by a few surviving dorsal column afferents, and hand use improves. We will evaluate the relationships between (1) the recovery of hand use, (2) the time course of the reactivation of cortex, (3) the recovery of response properties of cortical neurons, (4) the sprouting and growth of surviving dorsal column afferents in the cuneate nucleus of the lower brainstem to contact more neurons, and (5) the cellular and histochemical consequences in the cuneate nucleus of partial deafferentation. In addition, we will evaluate the effectiveness of two treatments, (6) chondroitinase ABC and (7) anti-Nogo-A, on sprouting new growth of surviving dorsal column afferents in the cuneate nucleus. The research is designed to provide an understanding of the major mechanisms of recovery of somatosensory system function after a sensory loss in humans, and to help develop favorable therapeutic approaches for humans with sensory loss after spinal cord injury.

Public Health Relevance

The proposed research seeks to evaluate the hypothesis that a few preserved sensory afferents in the dorsal columns of the spinal cord injury can mediate the recovery of hand use by sprouting to activate a large population of neurons in the brainstem and thereby, the cortex. The proposed research will also evaluate two treatments that are likely to promote the growth of the preserved sensory afferents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS016446-33
Application #
8512797
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Gnadt, James W
Project Start
1980-07-01
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
33
Fiscal Year
2013
Total Cost
$412,592
Indirect Cost
$148,110
Name
Vanderbilt University Medical Center
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Liao, Chia-Chi; Reed, Jamie L; Qi, Hui-Xin et al. (2018) Second-order spinal cord pathway contributes to cortical responses after long recoveries from dorsal column injury in squirrel monkeys. Proc Natl Acad Sci U S A 115:4258-4263
Cerkevich, Christina M; Kaas, Jon H (2018) Corticocortical projections to area 1 in squirrel monkeys (Saimiri sciureus). Eur J Neurosci :
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Qi, Hui-Xin; Reed, Jamie L; Franca, Joao G et al. (2016) Chronic recordings reveal tactile stimuli can suppress spontaneous activity of neurons in somatosensory cortex of awake and anesthetized primates. J Neurophysiol 115:2105-23

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