The death of neurons during the development of the central nervous system is a normal sequela of the overproduction of neurons. The proposed experiments will test the hypothesis that naturally occurring neuronal death contributes to pattern formation within the central nervous system. The subject of these experiments will be the rat trigeminal/somatosensory system because of the high topographic organization which is evident at all levels of this hierarchical system. Dying neurons will be identified immunohistochemically using a monoclonal antibody, Alz-50. This antibody is directed against a protein that has been purified from the brains of alzheimer's patients. These experiments will extend our previous studied on the generation, migration, and death of neurons in the principal sensory nucleus of the trigeminal nerve (PSN). The distribution, ultrastructure, and protein synthesis of the Alz-50- immunoreactive neurons will be examined. The studies on protein synthesis will examine transcription and translation using autoradiographic localization of [3H]uracil and [3H]leucine, respectively, in immunoreactive neurons. The second segment of this grant addresses the role of neuronal death in sculpting the pattern of neurons and connections within the trigeminal/somatosensory system. The time of origin of dying neurons in the PSN will be determined whether early-generated neurons die before late- generated neurons. Subsequently, our examination of Alz-50- immunoreactivity will be extended to the developing ventrobasal thalamus and somatosensory cortex to determine if neuronal death, like neuronal generation, follows a hierarchical order. Most PSN neurons project axons to the thalamus and these neurons are arranged in a barreloid pattern. The proposed experiments will assess whether neuronal death within and outside the barreloids is similar by examining the distribution of Alz-50- immunoreactive neurons and the pattern of retrogradely labeled trigeminothalamic projection neurons and/or of cytochrome oxidase histochemical staining. the last experiment, the effect of afferentation on neuronal survival will be examined by ablating the trigeminal ganglia or by maintaining the population of overproduced neurons in the trigeminal ganglia with administrations of nerve growth factor. These studies will examine the role of neuronal death in the development of the nervous system and provide a basis for our understanding of the pathology associated with congenital craniofacial malformations.
Showing the most recent 10 out of 178 publications
