Brevican immunoreactivity in the mouse cochlea during development and following noise-induced hearing loss

Abstract Perineuronal nets (PNNs) regulate synaptic stabilization and neural circuit development in the central nervous system. Although BCAN-associated extracellular matrix specializations have been described in the cochlea, their developmental organization and response to acoustic injury remain poorly understood. Here we characterized BCAN-associated extracellular matrix in the developing and adult mouse cochlea and examined changes following noise-induced hearing loss (NIHL). HAPLN1 and neurocan were broadly detected around inner hair cells from postnatal day 7 (P7), whereas BCAN immunoreactivity was not detected at P7 but was detectable around the inner hair cell (IhC) region at P14. RNA in situ hybridization and exploratory analysis of published single-cell transcriptomic datasets characterized developmental patterns of BCAN mRNA signals in spiral ganglion-associated cell populations. Three-dimensional cochlear clearing and light-sheet imaging qualitatively revealed BCAN immunoreactivity surrounding a subset of cell bodies in the auditory nerve transitional region of adult cochleae. Following permanent-threshold-shift–inducing noise exposure, BCAN immunoreactivity was markedly reduced in the IhC region and appeared less prominent around cell bodies in the auditory nerve transitional region. These findings further characterize BCAN-associated extracellular matrix patterns in the mouse cochlea and describe developmental changes in BCAN immunoreactivity and its reduction following severe NIHL.