This proposal intends to use the trigeminal system of felines to study the central effects of partial deafferentation (lesions to the trigeminal/V nerve) in the immature and the mature systems and relate these events to reorganization, remodeling, and plasticity in the system. Light (LM) and electron microscopic (EM) methods will be used to analyze synaptic plasticity as demonstrated by immunocytochemical localization of selected primary afferent and intrinsic neurotransmitters, nerve growth factor receptor, and a growth-associated protein. Although the entire brainstem trigeminal system will be studied, emphasis will be directed toward superficial laminae of the caudal subnucleus caudalis as this is a major pain relay and integration region. Two ages of feline will be used, 3 days and 12-18 months of age. The lesion will be a partial rhizotomy in order to study the involvement of the """"""""spared"""""""" primary afferents in the central reorganization. The principle primary afferent peptide to be studied will be calcitonin-gene-related peptide (CGRP), and the intrinsic will be gamma amino butyric acid (GABA/GAD). Antibodies to nerve growth factor receptor (NGFR) and a growth-associated protein (GAP-43) will be used to label and study """"""""growth processes"""""""" that may be involved in the deafferentation- induced remodeling. Qualitative data will be supplemented by quantitative analyses in selected cases of LM material. The main hypothesis is that CNS and synaptic responses to partial deafferentation will be time-dependent and will differ with the maturity of the system. The studies will provide here to for unavailable information as to transmitter-related, synaptic remodeling, possible evidence for """"""""sprouting"""""""" and reinnervation and the relationship to age and postinjury survival. This proposal is clearly inter-related with those of M. Bothwell, M.S. Grady and T. Reh each of whom are studying either growth factors in neural injury models or growth processes during development of in vitro systems. Thus the significant overlap of these four projects afford the unique possibility of cross- fertilization and a high potential for direct correlation of findings.
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