The combined effects of trkB and trkC mutations on the innervation of the inner ear

Previous research has demonstrated that only the two neurotrophins and thei r cognate receptors are necessary for the support of the inner ear innervat ion. However, detailed analyses of patterns of innervation in various combi nations of neurotrophin receptor mutants are lacking. We provide here such an analysis of the distribution of afferent and efferent fibers to the ear in various combinations of neurotrophin receptor mutants using the lipophil ic tracer DiI. In the vestibular system, trkC(+/-) heterozygosity aggravate s the trkB(-/-) mutation effect and causes almost complete loss of vestibul ar neurons. In the cochlea innervation, various mutations are each characte rized by specific topological absence of spiral neurons in Rosenthal's cana l of the cochlea. ti trkC(-/-) mutation alone or in combination with trkB(/-) heterozygosity causes absence of all basal turn spiral neurons and affe rent fibers extend from the middle turn to the basal turn along inner hair cells with little or no contribution to outer hair cells. Both types of bas al turn spiral neurons appear to develop and project via radial fibers to i nner and, more sparingly, outer hair cells. Simple trkB(-/-) mutations show a-reduction of fibers to outer hair cells in the apex and, less obvious, i n the basal turn. Basal turn spiral neurons may be the only neurons present at birth in the cochlea of a trkB(-/-) mutant mouse combined with trkC(+/- ) heterozygosity. In addition, the trkB(-/-) mutation combined with trkC(+/ -) heterozygosity has a patchy and variable loss of middle turn spiral neur ons in mice of different litters. Comparisons of patterns of innervation of afferent and efferent fibers show a striking similarity of absence of fibe rs to topologically corresponding areas. For example, in trkC(-/-) mutants afferents reach the basal turn, spiraling along the cochlea, rather than th rough radial fibers and efferent fibers follow the same pathway rather than emanating from intraganglionic spiral fibers. The data presented suggest t hat there are regional specific effects with some bias towards a specific s piral ganglion type: trkC is essential for support of basal turn spiral neu rons whereas trkB appears to be more important for middle and apical turn s piral neurons. (C) 1998 ISDN. Published by Elsevier Science Ltd. All rights reserved.