Lack of Brain-Derived Neurotrophic Factor Hampers Inner Hair Cell Synapse Physiology, But Protects against Noise-Induced Hearing Loss

• DOI: 10.1523/jneurosci.1247-12.2012
• Publication Date: 2012-08-01T18:04:20Z
• Authors: A. Zuccotti; S. Kuhn; S. L. Johnson; C. Franz; W. Singer; D. Hecker; H.-S. Geisler; I. Kopschall; K. Rohbock; K. Gutsche; J. Dlugaiczyk; B. Schick; W. Marcotti; L. Ruttiger; T. Schimmang; M. Knipper
• Keywords: Mice, Knockout; 0301 basic medicine; Hair Cells, Auditory, Inner; Brain-Derived Neurotrophic Factor; Blotting, Western; Otoacoustic Emissions, Spontaneous; PAX2 Transcription Factor; Cell Count; Blotting, Northern; beta-Galactosidase; Immunohistochemistry; Exocytosis; Cochlea; Mice; 03 medical and health sciences; Hearing Loss, Noise-Induced; Synapses; Evoked Potentials, Auditory, Brain Stem; Animals; Noise

The precision of sound information transmitted to the brain depends on the transfer characteristics of the inner hair cell (IHC) ribbon synapse and its multiple contacting auditory fibers. We found that brain derived neurotrophic factor (BDNF) differentially influences IHC characteristics in the intact and injured cochlea. Using conditional knock-out mice (BDNF(Pax2) KO) we found that resting membrane potentials, membrane capacitance and resting linear leak conductance of adult BDNF(Pax2) KO IHCs showed a normal maturation. Likewise, in BDNF(Pax2) KO membrane capacitance (ΔC(m)) as a function of inward calcium current (I(Ca)) follows the linear relationship typical for normal adult IHCs. In contrast the maximal ΔC(m), but not the maximal size of the calcium current, was significantly reduced by 45% in basal but not in apical cochlear turns in BDNF(Pax2) KO IHCs. Maximal ΔC(m) correlated with a loss of IHC ribbons in these cochlear turns and a reduced activity of the auditory nerve (auditory brainstem response wave I). Remarkably, a noise-induced loss of IHC ribbons, followed by reduced activity of the auditory nerve and reduced centrally generated wave II and III observed in control mice, was prevented in equally noise-exposed BDNF(Pax2) KO mice. Data suggest that BDNF expressed in the cochlea is essential for maintenance of adult IHC transmitter release sites and that BDNF upholds opposing afferents in high-frequency turns and scales them down following noise exposure.