The long-term objective of this research is to determine the mechanisms that underlie recovery and alteration of function following partial denervation of the adult mammalian central nervous system. Previous work on this project has led to new hypotheses to explain the immediate and long term physiological changes observed in spinal cord dorsal horn cells following interruption of descending pathways. It is proposed that the immediate decline in responsiveness to peripheral stimuli (""""""""spinal shock"""""""") is due to a loss of descending inhibition acting on interneurons that mediate presynaptic inhibition of afferent activity. It is postulated that the long term recovery of responsiveness to peripheral inputs and eventual return of spontaneous activity to normal levels are due to the development of denervation supersensitivity. The proposed experiments are designed to test these hypotheses and the alternative, more conventional hypotheses that spinal shock is due to mechanisms related to acute injury per se, and that long-term increases in responsiveness to peripheral stimuli are due to release of descending inhibition. To test whether spinal shock is due to injury per se, the applicant plans to measure dorsal horn cell responsiveness to peripheral stimuli following acute dorsolateral funiculus lesions and compare this with responsiveness under acute blockade of the DLF by lidocaine microinjection. To test whether dorsal horn cells are under tonic descending postsynaptic inhibition, intracellular methods will be used to measure their membrane potentials before and after lidocaine blockade of the DLF. To test whether primary afferent fibers are under tonic presynaptic inhibition, dorsal root potentials and microstimulation thresholds of primary afferent terminals will be measured before and after lidocaine blockade. To test for the development of denervation supersensitivity. The effects of microinjecting serotonin and peptide neurotransmitters on the response properties of dorsal horn neurons will be evaluated in normal and DLF lesion animals at survival times from < 1 to 60 days. These studies are relevant to our understanding of the physiological consequences of central nervous system injury, and of the ability of the nervous system to adapt to such injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS019523-07
Application #
3399602
Study Section
Neurology A Study Section (NEUA)
Project Start
1982-09-01
Project End
1991-08-31
Budget Start
1988-09-25
Budget End
1989-08-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Good Samaritan Hosp & Medical Center(Prtlnd,OR)
Department
Type
DUNS #
City
Portland
State
OR
Country
United States
Zip Code
97210
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Bernau, N A; Dawson, S D; Kane, L A et al. (1993) Changes in substance P and 5-HT binding in the spinal cord dorsal horn and lamina 10 after dorsolateral funiculus lesions. Brain Res 613:106-14
Pubols, L M; Bernau, N A; Kane, L A et al. (1992) Distribution of 5-HT1 binding sites in cat spinal cord. Neurosci Lett 142:111-4
Millecchia, R J; Pubols, L M; Sonty, R V et al. (1991) Influence of map scale on primary afferent terminal field geometry in cat dorsal horn. J Neurophysiol 66:696-704
Pubols, L M; Simone, D A; Bernau, N A et al. (1991) Anesthetic blockade of the dorsolateral funiculus enhances evoked activity of spinal cord dorsal horn neurons. J Neurophysiol 66:140-52
Pubols, L M (1990) Characteristics of dorsal horn neurons expressing subliminal responses to sural nerve stimulation. Somatosens Mot Res 7:137-51
Pubols, L M; Bowen, D C (1988) Lack of central sprouting of primary afferent fibers after ricin deafferentation. J Comp Neurol 275:282-7
Pubols, L M; Foglesong, M E (1988) Acute and chronic effects of the neurolytic agent ricin on dorsal root ganglia, spinal cord, and nerves. J Comp Neurol 275:271-81
Pubols, L M; Hirata, H; Brown, P B (1988) Temporally dependent changes in response properties of dorsal horn neurons after dorsolateral funiculus lesions. J Neurophysiol 60:1253-67
Pubols, L M; Foglesong, M E; Vahle-Hinz, C (1986) Electrical stimulation reveals relatively ineffective sural nerve projections to dorsal horn neurons in the cat. Brain Res 371:109-22