Journal
FRONTIERS IN NEUROSCIENCE
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2019.00620
Keywords
cochlea; ribbon synapses; noise-induced hearing loss; macrophages; fractalkine; C57BL/6 mice
Categories
Funding
- National Institutes of Health
- National Institute on Deafness and Other Communication Disorders [R03DC015320, R01DC006283]
- R03 grant
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Noise trauma causes loss of synaptic connections between cochlear inner hair cells (IHCs) and the spiral ganglion neurons (SGNs). Such synaptic loss can trigger slow and progressive degeneration of SGNs. Macrophage fractalkine signaling is critical for neuron survival in the injured cochlea, but its role in cochlear synaptopathy is unknown. Fractalkine, a chemokine, is constitutively expressed by SGNs and signals via its receptor CX(3)CR1 that is expressed on macrophages. The present study characterized the immune response and examined the function of fractalkine signaling in degeneration and repair of cochlear synapses following noise trauma. Adult mice wild type, heterozygous and knockout for CX(3)CR1 on a C57BL/6 background were exposed for 2 h to an octave band noise at 90 dB SPL. Noise exposure caused temporary shifts in hearing thresholds without any evident loss of hair cells in CX(3)CR1 heterozygous mice that have intact fractalkine signaling. Enhanced macrophage migration toward the IHC-synaptic region was observed immediately after exposure in all genotypes. Synaptic immunolabeling revealed a rapid loss of ribbon synapses throughout the basal turn of the cochlea of all genotypes. The damaged synapses spontaneously recovered in mice with intact CX(3)CR1. However, CX(3)CR1 knockout (KO) animals displayed enhanced synaptic degeneration that correlated with attenuated suprathreshold neural responses at higher frequencies. Exposed CX(3)CR1 KO mice also exhibited increased loss of IHCs and SGN cell bodies compared to exposed heterozygous mice. These results indicate that macrophages can promote repair of damaged synapses after moderate noise trauma and that repair requires fractalkine signaling.
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