Ultrastructural maturation of the endbulb of Held active zones comparing wild-type and otoferlin-deficient mice.

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 mice. During maturation, SV numbers at endbulb AZs increased in wild-type mice but were found to be reduced in mice. The SV population at a distance of 0-15 nm was most strongly affected. Finally, overall SV diameters decreased in animals during maturation.