Activity influences on neuronal connectivity within the auditory pathway

Hypothesis: Sensorineural hearing loss may be associated with altered patte rns of neuronal connections within the central auditory pathway. Study Desi gn: The cat auditory system was used to address the relative importance of impulse traffic within the auditory nerve in maintaining central nervous sy stem connections, Methods: Acute, unilateral deafness was induced by tetrod otoxin intoxication of cochlear hair cells, Analysis focused on the structu ral patterns of contact between auditory nerve endings called end bulbs of Held and their target neurons, Specifically, end bulb morphology and target cell size within the cochlear nucleus were examined. Highly specialized sy naptic contacts at this junction provide a powerful site for study. Results : The principal finding was that abolished activity in the auditory nerve c aused nerve endings to assume a different shape, typified by more branching and smaller terminal swellings. The new shape is one typically associated with only a subpopulation of fibers in normal-hearing cats-those exhibiting a high-threshold, low-spontaneous activity profile. This result implies th at abolished activity alters patterns of nerve fiber contact with second-or der neurons, Tetrodotoxin produced differential effects on subpopulations o f target neurons within the brainstem and is interpretable on the basis of "weighing" synaptic inputs. Second-order neurons that receive large axosoma tic inputs from their parent fiber were significantly smaller than neurons that receive small, axodendritic terminals. Thus, attenuated auditory activ ity may produce differential effects across the auditory pathway, thereby d isrupting the normal balance of inputs into synaptic stations. Conclusions: Impulse traffic is a critical factor in the interaction between the ear an d central auditory stations and appears necessary for the maintenance of ke y synapses. As hearing disorders with impaired comprehension may be modeled by studies of auditory deafferentation, these observations extend the poss ibility that changes in central neuronal connections underlie reduced capab ilities for processing restored auditory input.