Abstract
Early cochlear development is marked by an exuberant outgrowth of neurites that innervate multiple targets. The establishment of mature cochlear neural circuits is, however, dependent on the pruning of inappropriate axons and synaptic connections. Such refinement also occurs in the central nervous system (CNS), and recently, genes ordinarily associated with immune and inflammatory processes have been shown to play roles in synaptic pruning in the brain. These molecules include the major histocompatibility complex class I (MHCI) genes, H2-Kb and H2-Db, and the complement cascade gene, C1qa. Since the mechanisms involved in synaptic refinement in the cochlea are not well understood, we investigated whether these immune system genes may be involved in this process and whether they are required for normal hearing function. Here we report that these genes are not necessary for normal synapse formation and refinement in the mouse cochlea. We further demonstrate that C1qa expression is not necessary for normal hearing in mice but the lack of expression of H2-Kb and H2-Db causes hearing impairment. These data underscore the importance of the highly polymorphic family of MHCI genes in hearing in mice and also suggest that factors and mechanisms regulating synaptic refinement in the cochlea may be distinct from those in the CNS.
Highlights
In the sensory epithelium of organ of Corti, information about the timing, frequency and intensity of sounds is transmitted from and to the hair cells via highly organized synapses
The mature organ of Corti contains two types of sensory cells known as inner (IHC) and outer hair cells (OHCs) that are innervated by the spiral ganglion neurons (SGNs)
The age of onset of hearing in mice is around postnatal day 12 (P12), with synaptic refinement and functional maturation occurring during the first two postnatal weeks
Summary
In the sensory epithelium of organ of Corti, information about the timing, frequency and intensity of sounds is transmitted from and to the hair cells via highly organized synapses. The mature organ of Corti contains two types of sensory cells known as inner (IHC) and outer hair cells (OHCs) that are innervated by the spiral ganglion neurons (SGNs). SGI project branched neurites that innervate several targets including IHCs and OHCs. OHCs are mainly innervated with afferent fibers at birth. Several growth factors and guidance cues such as neurotrophins and ephrins are involved in spiral ganglion outgrowth, attraction, and repulsion. These factors have been identified, the specific molecular cues necessary for afferent/efferent cochlear fiber refinement remain poorly understood and warrant further investigation
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