The long-term aims of the proposed research are: (1) to uncover mechanisms governing the development of structure and function in central trigeminal (V) structures, (2) to assess the central structural and functional consequences of peripheral V nerve injury, and (3) to elucidate mechanisms responsible for injury-induced functional reorganization in the V neuraxis. Rat trigeminal (V) second-order neurons will serve as the model system because much is known of their normal development, structure, function and presynaptic inputs, as well as their responses to V nerve injury. Since these cells are important for oro-facial pain processing and behavior, clinically meaningful data will result. Four groups of experiments are proposed: (1) Quantitative electron microscopic method will be used to assess the extent and time course of degeneration and reactive synaptogenesis at birth. Parallel studies will examine the extent, distribution and likely sources of higher-order synapses in these 2 regions using anterograde labeling of V primary afferent terminals and immunohistochemical staining of higher-order aminergic and GABAergic terminals. (2) Retrograde tracing, extra- and intracellular recording and HRP labeling techniques will be used to study the effects of tetrodotoxin application to the morphology and receptive fields. These data permit a test of the hypothesis that neonata nerve injury effects are mediated by changes in the patterning of presynaptic activity. (3) To assess the extent to which the structure and function of neonatally deafferented brainstem cells are shaped by residual inputs in development, newborn rats will sustain injury to selected whisker follicles. Cytochrome oxidase, Golgi, retrograde labeling, and intracellular recording and HRP labeling techniques will then be used to compare V second-order cells receiving spared or regenerate infraorbital inputs. (4) To determine whether injury-induced changes in cell structure reflect the maintenance of a transient development state, V brainstem cells will be visualized at varying postnatal intervals by Golgi impregnation or intracellular HRP in a slice preparation. Taken together, these 4 studies test the general hypothesis that V primary afferent inputs determine V second-order survival, structure, function and higher-order inputs. Interpretation of these data, however, requires parallel analysis of injury sequelae at other levels of the V neuraxis. These experiments constitute Projects 1-3 and 5-7 of this Program Project.