Ultrastructural maturation of the endbulb of Held active zones comparing wild-type and otoferlin-deficient mice
Anika Hintze,
Mehmet Gültas,
Esther A. Semmelhack,
Carolin Wichmann
Affiliations
Anika Hintze
Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience, InnerEarLab and Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, 37075 Göttingen, Germany; Collaborative Research Center 1286, University of Göttingen, Göttingen, Germany; Göttingen Graduate School for Neurosciences, Biophysics and Molecular Biosciences, University of Göttingen, Göttingen, Germany
Mehmet Gültas
Breeding Informatics Group, Department of Animal Sciences, Georg-August-University Göttingen, Göttingen, Germany
Esther A. Semmelhack
Developmental, Neural, and Behavioral Biology MSc/PhD Program, University of Göttingen, Göttingen, Germany
Carolin Wichmann
Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience, InnerEarLab and Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, 37075 Göttingen, Germany; Collaborative Research Center 1286, University of Göttingen, Göttingen, Germany; Corresponding author
Summary: Endbulbs of Held are located in the anteroventral cochlear nucleus and present the first central synapses of the auditory pathway. During development, endbulbs mature functionally to enable rapid and powerful synaptic transmission with high temporal precision. This process is accompanied by morphological changes of endbulb terminals. Loss of the hair cell-specific protein otoferlin (Otof) abolishes neurotransmission in the cochlea and results in the smaller endbulb of Held terminals. Thus, peripheral hearing impairment likely also leads to alterations in the morphological synaptic vesicle (SV) pool size at individual endbulb of Held active zones (AZs). Here, we investigated endbulb AZs in pre-hearing, young, and adult wild-type and Otof−/− mice. During maturation, SV numbers at endbulb AZs increased in wild-type mice but were found to be reduced in Otof−/− mice. The SV population at a distance of 0–15 nm was most strongly affected. Finally, overall SV diameters decreased in Otof−/− animals during maturation.
