The long term goal of this research has been to characterize the neuronal circuitry involved in the presynaptic control of the synaptic effectiveness of primary afferents in the mammalian spinal cord and to disclose the role played by presynaptic inhibition in sensory-motor integration. Most of the effort made during the next grant period will be addressed to document, in the anesthetized or decerebrated cat, the selectivity of the control exerted by segmental and supraspinal inputs on the pathways mediating primary afferent depolarization (PAD) of muscle and cutaneous afferents. The working hypothesis is that the intraspinal branches of afferent fibers are not obliged routes for information transmission but represent potential routes that can be used to direct the information flow to different sets of neurons according to the function to be performed. To this end, the effects of sensory and descending inputs on the pathways leading to PAD of two collaterals of individual Ia, Ib or cutaneous fibers, one collateral ending within the intermediate nucleus or dorsal horn at the L6 segmental level, and the other collateral ascending to Clarke s columns at the L3 level or to the dorsal column nuclei, respectively, will be compared. PAD will be inferred from changes in the intraspinal threshold of each collateral. Differences in the magnitude of the effects will be attributed to selectivity in the action exerted by the stimulated pathways on both collaterals. The effects of reversible spinalization on the resting PAD and on the PAD evoked by sensory and descending stimuli in segmental (L6) and ascending (L3) collaterals of the same muscle or cutaneous afferent will also be examined, as well as the inhibition of the resting and evoked PAD in Ia fibers following conditioning stimulation of cutaneous and joint nerves. Previous investigations have indicated that stimulation of the reticular formation produces PAD in a substantial number of afferent fibers reconnected with muscle spindles 1-3 months after a peripheral nerve crush. These effects have been attributed to a reorganization of the spinal pathways mediating PAD of the damaged fibers. Experiments proposed here are designed to examine i) if the PAD produced in afferents reconnected with muscle spindles is associated with presynaptic inhibition ii) the GABAergic nature of the PAD and of the presynaptic inhibition produced in the reconnected afferents iii) the extent to which the PAD produced by stimulation of the bulbar reticular formation is restricted to the damaged afferents and iv) possible changes in the effects produced by other descending inputs (cerebral cortex, raphe nuclei and red nucleus). A third project aims to examine the functional relationship between populations of dorsal horn neurons and intermediate nucleus interneurons mediating non-reciprocal postsynaptic inhibition (class I) or PAD (class II). Computational techniques will be used to disclose a) the spinal potentials which appear in synchrony with the spontaneous activity of class I or class II interneurons, b) the instraspinal location of the corresponding cord potentials, c) the changes produced when the extracellular field potentials and interneuronal activity evoked by stimulation of muscle and cutaneous afferents and by descending (reticulo-spinal and cortico-spinal) inputs is preceded by cord potentials associated with the activity of class I or class II interneurons. These issues are relevant for the understanding of the functional relationships between defined sets of spinal interneurons and their possible role in the modulation of information conveyed by afferent fibers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS009196-25
Application #
2504327
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Baughman, Robert W
Project Start
1990-12-01
Project End
2000-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
25
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Polytechnic Institute
Department
Type
DUNS #
City
Mexico
State
Country
Mexico
Zip Code