| Neuronal connections in developing animals are determined by genetic factors and refined by electrical activity. Before the onset of hearing, patterned spontaneous activity originating in the cochlea activates groups of adjacent hair cells which then excite neurons throughout the auditory pathway. To understand the consequences of minimal spontaneous activity and absence of acoustically driven activity on connections between auditory nerve fibers and their bushy cell targets in the cochlear nucleus, I examined a mouse mutant in which otoferlin, the putative calcium sensor in hair cells, has a point mutation in one of its calcium binding domains. This mutation results in no immunoreactivity for otoferlin and little or no calcium induced exocytosis from inner hair cells after P3. Cochlear function is normal but the mice are profoundly deaf.;The cochlear nuclei of mutant mice have normal organization but the ventral cochlear nucleus is small. Auditory nerve fibers terminate on bushy cells in the ventral cochlear nucleus with end bulbs of Held that are smaller and wispier in deaf animals. Hearing controls receive an average of 2 auditory nerve fibers per bushy cell, while mutants receive input from about 2.5 auditory nerve fibers. Each of those auditory nerve fibers delivers more current in deaf mutants relative to hearing controls, about 4.8 nA rather than 3.4 nA. The maximal currents delivered by end bulbs are almost twice as large in mutant mice as in hearing controls, 13 nA compared with 7 nA, but depress more when auditory nerve fibers are stimulated repetitively. Intrinsic properties of bushy cells in deaf mutant mice were similar to those of hearing controls except that bushy cells from mutant mice could be driven to fire action potentials with less steep depolarizations.;I also examined a mutant mouse that hears but whose neuronal circuits are disorganized. The auditory nerve fibers of mice that lack natriuretic peptide receptor 2, fail to bifurcate normally in the nerve root of the ventral cochlear nucleus. In these mice the tonotopic organization of auditory nerve fiber projections and a of second order projection from the dorsal to the ventral cochlear nuclei are disorganized. |
