The central projections of intracellularly labeled auditory nerve fibers in cats: an analysis of terminal morphology.

The axons of physiologically characterized spiral ganglion neurons (type I) were stained throughout their arborizations in the cochlear nucleus by the intracellular injection of horseradish peroxidase (HRP). The tips of the axonal branches were marked by distinct swellings, ranging in size and shape from small boutons to large perisomatic ramifications. Electron microscopic analysis of such swellings revealed ultrastructural features characteristic of primary auditory synapses, consistent with the hypothesis that terminal swellings identifiable in the light microscope represent presynaptic endings. On the basis of light microscopic differences in size, these endings were organized into three categories. Endings of relatively small size (terminal boutons, free endings, boutons with filopodia, string endings, and small complex endings) composed 94% of all terminal endings. Within this category of small endings, there were predictable variations in relative size and regional distribution that related to the spontaneous discharge rate (SR) of the fiber. The endings of low and medium SR fibers (SR less than or equal to 18 spikes/second) were smaller on average than those of high SR fibers (SR greater than 18 spikes/second). Furthermore, there were more endings arising from the ascending branch than from the descending branch when comparing fibers of the low and medium SR group with those of the high SR group. There were not, however, obvious morphological features of this ending category that correlated with the characteristic frequency (CF, the pure tone frequency to which the neuron is most sensitive). A second category contained medium-sized complex endings, most of which formed axosomatic contacts. This category composed 4% of the population and was found in close proximity to the perikarya of globular, octopus, and spherical cells. The endings from low and medium SR fibers were smaller on average than those from high SR fibers. These endings did not vary in their parent branch distribution with respect to fiber SR, nor did they exhibit morphological features that correlated with fiber CF. The third category contained large complex endings (endbulbs of Held) and composed 2% of the ending population. Within the anteroventral cochlear nucleus, these large, complex endings made axosomatic contact with spherical cells in the anterior division and with globular cells in the posterior division. There were no systematic variations in ending size or branch distribution that correlated with fiber SR. There was, however, a relationship between ending size and fiber CF such that fibers having CFs below 4 kHz gave rise to the largest endbulbs.

The potentiation of ototoxicity when aminooxyacetic acid and kanamycin are co-administered.

Aminooxyacetic acid (AOAA) has been shown to confer protection against noise-induced cochlear trauma [3]. We, therefore, decided to study the possible protective effect of AOAA against kanamycin (KM) ototoxicity and found, instead, that AOAA potentiated the toxicity. To produce ototoxicity in guinea pigs, KM is usually given in 10-14 daily doses of 400 mg/kg s.c. However, when combined with a single dose of AOAA (8, 11, 15, or 25 mg/kg) a single 400 mg/kg dose of KM is sufficient to cause cochlear damage. Such animals show a negative Preyer's reflex between 1 to 3 days post injection. 21 days later hearing thresholds as detected electrocochleographically at 2, 4, 8, 12 and 16 kHz have changed drastically sometimes to the point of being undetectable. The damage seen histologically at this time is destruction of both inner and outer hair cells. A pharmacokinetic analysis of this potentiation revealed a slight prolongation of KM's sojourn in the inner ear. The possible mechanisms of this unexpected, marked potentiation are discussed but remain unknown.