Complexin-I is required for high-fidelity transmission at the endbulb of Held auditory synapse.
Complexins (CPXs I-IV) presumably act as regulators of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex, but their function in the intact mammalian nervous system is not well established. Here, we explored the role of CPXs in the mouse auditory system. Hearing was impaired in CPX I knock-out mice but normal in knock-out mice for CPXs II, III, IV, and III/IV as measured by auditory brainstem responses. Complexins were not detectable in cochlear hair cells but CPX I was expressed in spiral ganglion neurons (SGNs) that give rise to the auditory nerve. Ca(2+)-dependent exocytosis of inner hair cells and sound encoding by SGNs were unaffected in CPX I knock-out mice. In the absence of CPX I, the resting release probability in the endbulb of Held synapses of the auditory nerve fibers with bushy cells in the cochlear nucleus was reduced. As predicted by computational modeling, bushy cells had decreased spike rates at sound onset as well as longer and more variable first spike latencies explaining the abnormal auditory brainstem responses. In addition, we found synaptic transmission to outlast the stimulus at many endbulb of Held synapses in vitro and in vivo, suggesting impaired synchronization of release to stimulus offset. Although sound encoding in the cochlea proceeds in the absence of complexins, CPX I is required for faithful processing of sound onset and offset in the cochlear nucleus.
Strenzke
Nicola
N
InnerEarLab, Department of Otolaryngology, Göttingen University Medical School, D-37099 Göttingen, Germany.
Chanda
Soham
S
Kopp-Scheinpflug
Cornelia
C
Khimich
Darina
D
Reim
Kerstin
K
Bulankina
Anna V
AV
Neef
Andreas
A
Wolf
Fred
F
Brose
Nils
N
Xu-Friedman
Matthew A
MA
Moser
Tobias
T
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001306:Auditory Pathways / Q000502:physiology*; D003056:Cochlear Nerve / Q000502:physiology; D017626:Cochlear Nucleus / Q000378:metabolism*; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism; D006309:Hearing / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; C095992:complexin I; C095993:complexin II