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Rapid changes in protein synthesis and cell size in the cochlear nucleus following eighth nerve activity blockade or
1Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle 98195.
Abstract:
Destruction of the cochlea causes secondary changes in the central auditory pathway through transynaptic regulation. These changes appear to be mediated by an activity-dependent process and can be detected in the avian auditory system as early as 30 minutes after deafferentation. We compared the early changes in cochlear nucleus neurons following deafferentation by cochlea ablation with those seen following activity deprivation by perilymphatic tetrodotoxin (TTX) exposure. Protein synthesis and size of large spherical cells in the anteroventral cochlear nucleus (AVCN) of 14-day-old gerbils were measured during the first 48 hours after the manipulations. Both cochlea ablation and TTX produced a reliable decrease in protein synthesis by AVCN neurons (30-40%) by 1 hour. The magnitude of change in tritiated leucine incorporation was similar at all survival times, in both experimental groups. In contrast to the rapid changes in protein synthesis, the decrease in cell size was first evident 18 hours after TTX exposure and 48 hours after cochlea ablation. There was no significant change in protein synthesis or cell size in control groups at any of the survival times. These findings are consistent with changes in the avian auditory system in response to deafferentation and TTX exposure. Cochlea ablation and TTX exposure induced similar transneuronal changes, supporting the hypotheses that activity of auditory afferents in young mammals plays a regulatory role in the metabolism and morphology of their target neurons in the central auditory pathway, and that early changes following destruction of the peripheral receptor are due to reduction of activity-dependent interactions of presynaptic and postsynaptic cells.
Insights
Cochlear ablation or activity deprivation rapidly reduces protein synthesis in auditory neurons. Cell size changes occur later, indicating activity-dependent regulation in the central auditory pathway.
Area of Science:
- Neuroscience
- Auditory System Research
- Cellular Biology
Background:
- Cochlear destruction triggers secondary changes in the central auditory pathway via transynaptic regulation.
- These activity-dependent changes are observable in avian auditory systems shortly after deafferentation.
Purpose of the Study:
- To compare early changes in cochlear nucleus neurons after cochlea ablation versus activity deprivation using tetrodotoxin (TTX).
- To investigate the role of auditory afferent activity in regulating metabolism and morphology of central auditory pathway neurons in young mammals.
Main Methods:
- Gerbils (14-day-old) underwent either cochlea ablation or perilymphatic TTX exposure to induce deafferentation or activity deprivation.
- Protein synthesis (tritiated leucine incorporation) and cell size of anteroventral cochlear nucleus (AVCN) neurons were measured at various survival times (up to 48 hours).
Main Results:
- Both cochlea ablation and TTX significantly decreased AVCN neuron protein synthesis by 30-40% within 1 hour.
- Cell size reduction was observed later: 18 hours post-TTX and 48 hours post-cochlea ablation.
- No significant changes in protein synthesis or cell size were found in control groups.
Conclusions:
- Auditory afferent activity plays a crucial regulatory role in the metabolism and morphology of target neurons in the central auditory pathway of young mammals.
- Early post-lesion changes in the central auditory pathway are primarily due to reduced activity-dependent interactions between pre- and postsynaptic cells.