Neuroplastin expression is essential for hearing and hair cell PMCA expression

Lin X; Brunk MGK; Yuanxiang P; Curran AW; Zhang E; Stöber F; Goldschmidt J; Gundelfinger ED; Vollmer M; Happel MFK; Herrera-Molina, R


Hearing deficits are caused by particular mutations in the neuroplastin ( Nptn ) gene, which encodes a transmembrane recognition molecule of the immunoglobulin (Ig) superfamily. Using behavioral, electrophysiological, and in vivo imaging measurements, this study investigates whether the complete absence of neuroplastin or the loss of neuroplastin after normal development lead to hearing impairment in mice. Adult neuroplastin-deficient mice fail to behaviorally respond to white noise and show reduced baseline blood flow in the auditory cortex (AC) as revealed by singlephoton emission computed tomography (SPECT). In adult neuroplastin-deficient mice, tone evoked cortical activity was not detectable within the primary auditory field (A1) of the AC, although we observed non-persistent tone-like evoked activities in electrophysiological recordings of some young neuroplastin-deficient mice. Auditory brainstem recordings from adult neuroplastin-deficient mice confirm that these mice are deaf. Conditional ablation of neuroplastin in Nptn loxloxEmx1Cre mice reveals that behavioral responses to simple tones or white noise do not require neuroplastin expression by central glutamatergic neurons. The loss of neuronal neuroplastin in adult Nptn Δlox/loxPr CreERT mice after normal development does not fully compromise behavioral responses to sounds, however, hearing thresholds increase and effective prepulse inhibition (PPI) of the startle response can only be achieved using high prepulse intensities. Furthermore, we show that neuroplastin is required for expression of plasma membrane Calcium ATPases (PMCA) 1 and 2 in inner and outer hair cells, respectively, suggesting that altered Ca 2+ homeostasis underlies the observed hearing impairments. Our results demonstrate the importance of neuroplastin during development and for maintenance of the auditory system.

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Editorial: Springer
Fecha de publicación: 2021
Idioma: English