Rapid changes in cochlear nucleus cell size following blockade of auditory nerve electrical activity in gerbils

Publisher Website
Google Scholar
Abstract
Large spherical cells of the mammalian anteroventral cochlear nucleus (AVCN) receive direct excitatory input from auditory nerve axons. Trans‐synaptic regulation of neuronal cell size and cell number after cochlear ablation has been previously demonstrated in neonates of several vertebrate species, including the gerbil. Such changes may be related to loss of spontaneous or evoked auditory nerve electrical activity or to loss of activity‐independent factors. We have developed a method to chronically, yet reversibly, block auditory nerve electrical activity without violating the integrity of the inner ear. Tetrodotoxin (TTX) was embedded in an ethylene‐vinyl acetate copolymer resin (Elvax). A small piece of Elvax containing TTX was placed next to the round window membrane, which allowed TTX to diffuse into the inner ear. As a measure of the effectiveness of manipulation, the onset, duration, and magnitude of the auditory threshold shift were measured by the auditory brainstem response. The sound‐evoked response was abolished within 10 minutes of placement of TTX on the round window membrane. The duration of threshold shift was dose‐dependent and lasted 24–46 hours. Implants of Elvax without TTX did not produce a significant threshold shift. TTX, which blocks voltage‐gated sodium channels, did not abolish the potassium‐based cochlear microphonic response. The consequence of blocking afferent electrical activity on gerbil AVCN large spherical cells was examined by measuring their cross‐sectional area after each of four manipulations: unilateral auditory nerve action potential blockade with TTX; unilateral surgical cochlear ablation; ipsilateral TTX exposure/contralateral cochlear ablation; and unilateral sham operation (Elvax without TTX). Large spherical cells ipsilateral to cochlea TTX exposure were 21% smaller than contralateral large spherical cells. Cells ipsilateral to cochlear ablation were 25% smaller than contralateral cells. There was not a significant difference between the effect of cochlear ablation and TTX exposure on AVCN cell size and there was not a reliable effect of sham operation. These findings are consistent with previous work in the avian auditory system and support the hypothesis that electrical activity or the sequelae of electrical activity is a major factor in transneuronal regulation of cell size.