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We performed perforated patch-clamp recordings of Ca<jats:sup>2+<\/jats:sup>currents and exocytic membrane capacitance changes in IHCs of athyroid and TH-substituted<jats:italic>Pax8<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice during postnatal development. Ca<jats:sup>2+<\/jats:sup>currents remained elevated in athyroid IHCs at the end of the second postnatal week, when it had developmentally declined in wild-type and TH-rescued mutant IHCs. The efficiency of Ca<jats:sup>2+<\/jats:sup>influx in triggering exocytosis of the readily releasable vesicle pool was reduced in athyroid IHCs. Ribbon synapses were formed despite the TH deficiency. However, different from wild type, in which synapse elimination takes place at approximately the onset of hearing, the number of ribbon synapses remained elevated in 2-week-old athyroid IHCs. Moreover, the ultrastructure of these synapses appeared immature. Using quantitative reverse transcription-PCR, we found a TH-dependent developmental upregulation of the mRNAs for the neuronal SNARE (soluble<jats:italic>N<\/jats:italic>-ethylmaleimide-sensitive factor attachment protein receptor) proteins, SNAP25 (synaptosomal-associated protein of 25 kDa) and synaptobrevin 1, in the organ of Corti. These molecular changes probably contribute to the improvement of exocytosis efficiency in mature IHCs. IHCs of 2-week-old athyroid<jats:italic>Pax8<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice maintained the normally temporary efferent innervation. Moreover, they lacked large-conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>channels and KCNQ4 channels. This together with the persistently increased Ca<jats:sup>2+<\/jats:sup>influx permitted continued action potential generation. We conclude that TH regulates IHC differentiation and is essential for morphological and functional maturation of their ribbon synapses. We suggest that presynaptic dysfunction of IHCs is a mechanism in congenital hypothyroid deafness.<\/jats:p>","DOI":"10.1523\/jneurosci.3974-06.2007","type":"journal-article","created":{"date-parts":[[2007,3,21]],"date-time":"2007-03-21T18:24:47Z","timestamp":1174501487000},"page":"3163-3173","source":"Crossref","is-referenced-by-count":76,"title":["Maturation of Ribbon Synapses in Hair Cells Is Driven by Thyroid Hormone"],"prefix":"10.1523","volume":"27","author":[{"given":"Gaston","family":"Sendin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna 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