Development of primary axosomatic endings in the anteroventral cochlear nucleus of mice.

The endbulb of Held is a large synaptic ending that arises from the myelinated auditory nerve fibers. Endbulbs exhibit an elaborate pattern of terminal branching and produce extensive contact with the postsynaptic cell body. These structural features appear to underlie the tight coupling between presynaptic activity and postsynaptic spike discharges. As a first step toward understanding the relationship between environmental sounds and the development of these neural elements, we examined the age-related changes in the morphology of endbulbs of Held in CBA/J mice, a strain known to retain good hearing throughout life. Neurobiotin was injected into the modiolus of the cochlea in CBA/J mice ranging in age from postnatal day 1 to 7 months. Light microscopic analyses suggest that endbulbs of the CBA/J mice develop from small bouton endings at birth into large, highly branched structures in adults. This increase in structural complexity occurs mostly during the second through eighth postnatal weeks, and general stages of development can be defined. In addition, we compared endbulb structure between adult CBA/J mice and adult shaker-2 mice (Myo15sh2/sh2) and heterozygous littermates (Myo15+/sh2). The shaker-2 mouse carries a mutated myosin 15 gene that results in congenital deafness, presumably due to abnormally short stereocilia in hair cell receptors. Neurobiotin was injected into the modiolus of adult CBA/J, Myo15sh2/sh2, and Myo15+/sh2 mice. Endbulbs of deaf adult Myo15sh2/sh2 mice exhibited a striking reduction in terminal branching compared with those of CBA/J and Myo15+/sh2 mice. Notably, the abnormal endbulbs of Myo15sh2/sh2 mice do not resemble immature endbulbs of normal-hearing mice, suggesting that deafness does not simply arrest development.