Our studies aim to identify and analyze the changes in spinal neural circuits which occur following primary deafferentation, using injection of proteolytic enzymes (pronase) into a peripheral nerve to selectively kill the ganglion cells of that nerve. We have previously demonstrated in the adult rat an expansion of small diameter saphenous afferents within the substantia gelatinosa, using WGA-HRP, 4 months following pronase injection of the sciatic nerve. The expansion of labelling may be evidence of collateral sprouting by noninjured primary afferents. We now intend to: 1) examine the fate of large diameter afferents using beta-CT-HRP; this will provide information on systems which are important in mechano- and proprioreception; 2) develop a median/ ulnar model similar to our current sciatic/saphenous model; this will allow us to examine other areas of primary afferent termination, including the cuneate n., external cuneate n, and the N. of Clarke, all of which receive topographically organized projections from both the median and the ulnar nerves; 3) quantitatively compare the terminal number, type and synaptic contacts of labeled terminals on the control and experimental sides at each site in which expansion of terminal fields is observed; this will provide an indication of the type of replacement that occurs and whether reorganization differs at each site; 4) determine the early time course of the terminal field expansions, to understand the changes which occur ultrastructurally over the period of sprout development; and 5) examine the neurochemical identity of the sprouted terminals and of their targets, using the immunogold postembedding labelling method combined with the tracer labeling of the afferents. These experiments will test the hypotheses that all classes of primary afferents may exhibit sprouting and that the type of reorganization which occurs may be partially determined by the site and original organization of the target area.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS028876-01
Application #
3415562
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1990-09-01
Project End
1993-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520