Activity influences on neuronal connectivity within the auditory pathway

Hypothesis: Sensorineural hearing loss may be associated with altered patterns of neuronal connections within the central auditory pathway. Study Design: The cat auditory system was used to address the relative importance of impulse traffic within the auditory nerve in maintaining central nervous system connections. Methods: Acute, unilateral deafness was induced by tetrodotoxin intoxication of cochlear hair cells. Analysis focused on the structural 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 synaptic contacts at this junction provide a powerful site for study. Results: The principal finding was that abolished activity in the auditory nerve caused 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 that abolished activity alters patterns of nerve fiber contact with second-order neurons. Tetrodotoxin produced differential effects on subpopulations of target neurons within the brainstem and is interpretable on the basis of 'weighing' synaptic inputs. Second-order neurons that receive large axosomatic inputs from their parent fiber were significantly smaller than neurons that receive small, axodendritic terminals. Thus, attenuated auditory activity may produce differential effects across the auditory pathway, thereby disrupting the normal balance of inputs into synaptic stations. Conclusions: Impulse traffic is a critical factor in the interaction between the ear and central auditory stations and appears necessary for the maintenance of key synapses. As hearing disorders with impaired comprehension may be modeled by studies of auditory deafferentation, these observations extend the possibility that changes in central neuronal connections underlie reduced capabilities for processing restored auditory input.