The Presynaptic Function of Mouse Cochlear Inner Hair Cells during Development of Hearing

Abstract

Before mice start to hear at approximately postnatal day 10, their cochlear inner hair cells (IHCs) spontaneously generate Ca²⁺ action potentials. Therefore, immature IHCs could stimulate the auditory pathway, provided that they were already competent for transmitter release. Here, we combined patch-clamp capacitance measurements and fluorimetric [Ca²⁺]_i recordings to study the presynaptic function of IHCs during cochlear maturation. Ca²⁺-dependent exocytosis and subsequent endocytic membrane retrieval were already observed near the date of birth. Ca²⁺ action potentials triggered exocytosis in immature IHCs, which probably activates the auditory pathway before it becomes responsive to sound. IHCs underwent profound changes in Ca²⁺-channel expression and secretion during their postnatal development. Ca²⁺-channel expression increased toward the end of the first week, providing for large secretory responses during this period and thereafter declined to reach mature levels. The efficacy whereby Ca²⁺ influx triggers exocytosis increased toward maturation, such that vesicle fusion caused by a given Ca²⁺ current occurred faster in mature IHCs. The observed changes in Ca²⁺-channel expression and synaptic efficacy probably reflected the ongoing synaptogenesis in IHCs that had been described previously in morphological studies.