This application is designed to a) examine the sprouting response of undamaged and damaged trigeminal primary afferent neurons following neonatal peripheral nerve lesions and b) to study some of the mechanisms which may be important in the generation of lesion-induced central terminal arbor abnormalities. To accomplish these goals we propose the following three experiments: 1) The potential of undamaged trigeminal primary afferents to alter their central projections via sprouting, arbor expansion or arbor displacement will be examined by cauterizing all vibrissa follicles of the mystical pad with the exception of those in row C or D. Using intraaxonal and intracellular labeling techniques, we will determine the response of primary afferents with undisturbed peripheral terminations to partial denervation of their central target. 2) We will utilize quantitative electron microscopic techniques to investigate the impact of neonatal infraorbital (IO) nerve transection on the central terminal populations of two subsets of small diameter primary afferent neurons (substance P-like immunoreactive and fluoride resistant acid phosphatase- positive). By examining animals at sequenced intervals after the nerve injury we will determine if the number of terminals per unit area of the substantia gelatinosa and magnocellular region of subnucleus caudalis is maintained, decrease or increased (indicative of sprouting). 3) To determine the importance of patterned primary afferent activity in the development and maintenance of trigeminal primary afferent central terminal arbors, we will expose the IO nerve to tetrodotoxin beginning on the day of birth. This will inhibit primary afferent activity without transecting the nerve, thus causing no apparent disruption in the transport of any trophic substances important to information regarding the response of damaged and undamaged neurons to lesion-induced deafferentation of a portion of the trigeminal system. This knowledge has important clinical benefits in addition to its value as a contribution to our understanding of somatosensory development.
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