The research proposed will define the peripheral and central sequelae of trigeminal nerve damage and, in addition, determine whether these consequences can be altered by treatment with neuronal growth promoters such a bovine brain gangliosides. The application is composed of six projects, each of which will examine on aspect of the reorganization which follows transection of the infraorbital nerve in either adult or neonatal rats. PROJECT 1 will employ electron microscopic, multiple retrograde tracing and electrophysiological methods to address issues of ganglion cell survival and reorganization of peripheral connectivity. PROJECT 2 will use tranganglionic tracing and injection of individual, functionally characterized primary afferents with horseradish peroxidase (HRP) to determine the extent to which nerve damage or inactivation alters the primary afferent innervation of the trigeminal brainstem complex and whether changes in the central arbors of individual axons can be correlated with alterations in their peripheral connectivity. PROJECT 3 will concentrate upon potential changes in the brainstem organization. In these experiments, novel morphometric techniques will be employed to delineate the effects of both deafferentation and removal of targets upon the survival of trigeminal brainstem neurons. PROJECT 4 will employ retrograde tracing, electrophysiological and HRP injection techniques to delineate the effects of nerve damage or inactivation upon the morphology, response properties and projections of second order trigeminal neurons. PROJECT 5, like 4 and 3, will examine damage induced changes in the organization of the trigeminal brainstem complex. In these experiments, however, the emphasis will be upon monaminergic pathways which are well known to influence the responses of trigeminal neurons. PROJECT 6 will have as its focus studies concerned with the effects of treatment with bovine brain gangliosides upon neuronal survival and the events which surround and may influence axonal regeneration by surviving neurons. A parallel series of experiments will also examine the effects of gangliosides upon trigeminal ganglion cell survival and neuritogenesis in vitro.
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