Lack of brain-derived neurotrophic factor hampers inner hair cell synapse physiology, but protects against noise-induced hearing loss.
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.
Department of Otolaryngology, Head and Neck Surgery, Hearing Research Centre Tübingen, Molecular Physiology of Hearing, University of Tübingen, 72076 Tübingen, Germany.
Annalisa
A
Zuccotti
Stephanie
S
Kuhn
Stuart L
SL
Johnson
Christoph
C
Franz
Wibke
W
Singer
Dietmar
D
Hecker
Hyun-Soon
HS
Geisler
Iris
I
Köpschall
Karin
K
Rohbock
Katja
K
Gutsche
Julia
J
Dlugaiczyk
Bernhard
B
Schick
Walter
W
Marcotti
Lukas
L
Rüttiger
Thomas
T
Schimmang
Marlies
M
Knipper
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D002452:Cell Count; D003051:Cochlea / Q000254:growth & development / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005089:Exocytosis / Q000235:genetics / Q000502:physiology; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D006317:Hearing Loss, Noise-Induced / Q000235:genetics*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009622:Noise / Q000009:adverse effects; D017084:Otoacoustic Emissions, Spontaneous; D051762:PAX2 Transcription Factor / Q000235:genetics; D013569:Synapses / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D001616:beta-Galactosidase