RESUMO
During early postnatal development, afferent neurons of the cochlear (spiral) ganglion progressively refine their projections to auditory hair cells so that, by hearing onset, most cochlear nerve fibers innervate a single hearing receptor. One mechanism that might contribute to these changes in cochlear innervation is the programmed cell death (apoptosis) of developing neurons within the spiral ganglion. In the present study, we used the TUNEL method and morphological criteria to identify apoptotic cells within the spiral ganglion of the Mongolian gerbil during the first week of postnatal life when afferent projections to the cochlea are actively refined in this species. The locations of individual apoptotic spiral ganglion cells were mapped onto three-dimensional reconstructions of the entire ganglion for an age-graded series of gerbils to produce the first high-resolution, spatiotemporal maps of apoptotic ganglion cell death for the postnatal cochlea. We observed a significant increase in apoptosis in the spiral ganglion from postnatal day (P) 4 through P6. During this time, the most intense apoptotic activity occurred in regions of the spiral ganglion providing innervation to the lower middle and apical turns of the cochlea. The time course and regional variation of programmed cell death within the developing gerbil spiral ganglion are discussed in terms of the postnatal refinement of cochlear innervation and its possible functional significance for hearing in gerbils.
Assuntos
Apoptose/fisiologia , Diferenciação Celular/fisiologia , Cóclea/crescimento & desenvolvimento , Neurônios Aferentes/fisiologia , Gânglio Espiral da Cóclea/crescimento & desenvolvimento , Fatores Etários , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos , Mapeamento Encefálico , Contagem de Células , Cóclea/citologia , Gerbillinae , Células Ciliadas Auditivas/fisiologia , Marcação In Situ das Extremidades Cortadas , Vias Neurais/citologia , Vias Neurais/crescimento & desenvolvimento , Neurônios Aferentes/citologia , Gânglio Espiral da Cóclea/citologia , Fatores de TempoRESUMO
The auditory receptor epithelium of mammals receives efferent innervation from neurons within and surrounding the superior olivary complex of the brainstem (Warr [1975] J. Comp. Neurol. 161:159-181). Disruption of this pathway during early postnatal life, when olivocochlear axons are forming their final connections with auditory hair cells and nerve fibers, can lead to profound and permanent hearing impairments (Walsh et al. [1998] J. Neurosci. 18:3859-3869). Identification of the possible causes for this deterioration in auditory function requires a better understanding of the normal developmental interactions that occur between efferent axons and their target cells within the cochlea. To provide such information, we labeled developing efferent fibers at a constant location within the gerbil cochlea by using the fluorescent carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine perchlorate (DiI). The terminal arbors of these neurons were then reconstructed by using digital confocal microscopy. By postnatal day (P) 2, the efferent arbors associated with inner hair cells (IHCs) and outer hair cells (OHCs) displayed distinctly different morphologies closely resembling those described for adult animals (Brown [1987] J. Comp. Neurol. 260:605-619). Unlike their mature counterparts, however, P2 efferent axons frequently branched to contact both types of auditory hair cells. Unexpectedly, between P4 and P6, both IHC and OHC efferent axons produced additional branches that crossed the tunnel of Corti to invade the OHC zone. By P8, all of these supernumerary connections were eliminated, yielding completely segregated efferent pathways to IHCs and OHCs.