Superior olivary contributions to auditory system plasticity: medial but not lateral olivocochlear neurons are the source of cochleotomy-induced GAP-43 expression in the ventral cochlear nucleus.

Abstract

A unilateral cochlear lesion induces expression of the growth and plasticity-associated protein 43 (GAP-43) in fibers and their varicosities on specific types of postsynaptic profiles in the ventral cochlear nucleus (VCN), suggesting the induction of synaptic remodeling. One candidate population from which GAP-43 might emerge was neurons of the lateral olivocochlear (LOC) system residing in the lateral superior olive (LSO). Upon cochleotomy, these neurons express GAP-43 mRNA and GAP-43 protein. However, retrograde axonal tracing with Fast Blue or biotinylated dextran amine from VCN revealed that the number of 6.8 +/- 1.3 neurons in the whole ipsilateral LSO labeled in normal adult rats was distinctly small and did not rise after cochleotomy. Concluding that LOC neurons cannot be the source of GAP-43 in the VCN, we reinvestigated the pattern of GAP-43 in situ hybridization and found that, after cochleotomy, shell neurons in the regions surrounding the LSO and medial olivocochlear (MOC) neurons in the ventral nucleus of the trapezoid body up-regulated GAP-43 mRNA. We then lesioned these regions by means of stereotaxic injections of kainic acid. Destruction of shell neurons preceding an ipsilateral cochleotomy did not change the emergence of GAP-43 immunoreactivity in the VCN. However, if the contralateral MOC system was lesioned, the rise of GAP-43 immunoreactivity in VCN on the side of the cochleotomy was significantly reduced. We conclude that, after cochlear dysfunction, MOC neurons are the major (if not exclusive) source of synaptic reorganization in the VCN that could possibly entail compensatory activation of the affected ascending auditory pathway.