Developmental segregation in the afferent projections to mammalian auditory hair cells.

Abstract

The ammalian ear contains two types of auditory receptors, inner and outer hair cells, that lie in dose proximity to each other within the sensory epithelium of the cochlea. In adult mammals, these two classes of auditory hair cells are innervated by separate populations ofafferent neurons that differ strikingly in their cellular morphology and their pattern of arborization within the cochlea. At present, it Is unclear when or how these disinctive patterns of cochlear innervation emerge and become segregated during development. In the present study, an in vitro horseradish peroxidase labeling method was used to examine the formation of individual auditory neuron arbors at the same location within the apex of the developing gerbil cochlea. At birth, most cochlear neurons displayed peripheral arbors that embraced both inner and outer hair cell receptors. During the next 6 days, however, the arbors of individual cochlear afferents become confined to either the inner or outer hair cell zone, and thus there is a complete segregation of afferent innervation. This neural segregation occurs principally through the withdrawal of inappropriate connectimns to the outer hair cell ystem and is completed well before hearing commences.A central goal of neurobiology is to determine how developing neurons choose their specific synaptic partners. An excellent system for examining this issue is the mammalian auditory endorgan, the cochlea, since its pattern of innervation is among the most precise of any sensory or motor system. The adult cochlea contains two types of auditory receptors, termed inner (IHCs) and outer (OHCs) hair cells, which receive separate and highly distinctive patterns of afferent innervation. Ninety percent of all cochlear afferents project to individual IHCs via thick unbranched radial afferents, each of which terminates in a single synapse. The OHCs, on the other hand, receive a more diffuse innervation from a relatively few thin spiral afferents, each of which projects for hundreds of micrometers along the length of cochlea before branching to contact from 5 to 50 receptorsUltrastructural studies have provided evidence for substantial ontogenic changes in the form, number, and spatial arrangement of synapses between mammalian auditory receptors and cochlear nerve fibers (9-16). To understand the process by which these synaptic patterns are adjusted during development, however, it is necessary to examine the early morphological changes that occur in the formation of indi- In the present investigation, I have employed an in vitro horseradish peroxidase (HRP) method that permits labeling of small populations of auditory nerve fibers at any location within the developing cochlea. The Mongolian gerbil was selected for study since this species displays a prolonged period of postnatal cochlear maturation. In addition, the gerbil cochlea, like that of the mouse (26), lengthens <10% after birth, from an average of 10.8 mm in the newborn (unpublished data) to 12.1 mm in the adult (27), which greatly reduces ...

Relationship between the Development of Outer Hair Cell Electromotility and Efferent Innervation: A Study in Cultured Organ of Corti of Neonatal Gerbils

“…4 D). Similar observations at the apex of newborn gerbils (Echteler, 1992) and a newborn cat (Perkins and Morest, 1975) were reported previously. One might notice the low density of spiral ganglion cells and radial fibers in the culture.…”

“…The gerbil offers several important advantages for the study of development and interaction between nerve fibers and hair cells. As in other altricial rodents such as rat, mouse, and hamster (Echteler, 1992), the onset of hearing in gerbil does not occur until at least 10 d after birth (Woolf and Ryan, 1984). Therefore, important periods of development in the auditory periphery that precede the onset of hearing are more amenable to direct observation in this animal than in precocial mammals (primates, cats, and guinea pigs) whose hearing begins prenatally or at birth (Rubel, 1978;Horner et al, 1987).…”

“…However, ultrastructural studies in developing gerbils show that in the first two postnatal days OHCs are exclusively innervated by afferents. During the next few days, efferent fibers approach OHCs (Pujol et al, 1978;Echteler, 1992) as the inappropriate connections of afferents to the OHC system withdraw. Labeling experiments in mouse and hamster indicate that efferent fibers contact OHCs ϳ4 -8 d after birth (Simmons et al, 1990;Sobkowicz, 1992).…”

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

“…Founded on the observation that type II afferents fail to face strong type I axon competition in the OHC region, EphA4 À type II afferents could not compete against multiple and dense type I connections at IHCs and prefer to project to OHCs. Such an explanation is not far from the idea that type I afferents may reach the OC earlier and occupy the available membrane surface on IHCs, thus leaving free synaptic space only on OHCs for type II fibers 37 . To precisely address this competition hypothesis, a mouse line devoid of type I SGNs should be created in order to observe whether, in the absence of competition, some type II SGNs connect the IHCs.…”

“…Perinatally, during HC innervation process, although type I fibres are specifically refined to basolateral regions of IHCs, some collateral branches (CBs) establish temporary synaptic contacts with OHCs that are pruned at later stages 5,37,38 . Importantly, numerous type I SGNs have both a main fibre refining to IHC and a CB forming a transient synapse with OHCs.…”