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The Journal of Neuroscience, March 21, 2007, 27(12):3163-3173; doi:10.1523/JNEUROSCI.3974-06.2007

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Cellular/Molecular
Maturation of Ribbon Synapses in Hair Cells Is Driven by Thyroid Hormone

Gaston Sendin,¹ Anna V. Bulankina,¹ Dietmar Riedel,² and Tobias Moser¹

¹InnerEarLab, Department of Otolaryngology and Center for Molecular Physiology of the Brain, Göttingen University Medical School, 37075 Göttingen, Germany, and ²Electron Microscopy Group, Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany

Correspondence should be addressed to Tobias Moser, InnerEarLab, Department of Otolaryngology, University of Göttingen, Center for Molecular Physiology of the Brain, Bernstein Center for Computational Neuroscience, 37099 Göttingen, Germany. Email: tmoser{at}gwdg.de

Ribbon synapses of inner hair cells (IHCs) undergo developmental maturation until after the onset of hearing. Here, we studied whether IHC synaptogenesis is regulated by thyroid hormone (TH). We performed perforated patch-clamp recordings of Ca²⁺ currents and exocytic membrane capacitance changes in IHCs of athyroid and TH-substituted Pax8^–/– mice during postnatal development. Ca²⁺ 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 Ca²⁺ 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 N-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 Pax8^–/– mice maintained the normally temporary efferent innervation. Moreover, they lacked large-conductance Ca²⁺-activated K⁺ channels and KCNQ4 channels. This together with the persistently increased Ca²⁺ 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.

Key words: thyroid hormone; ion channel; ribbon synapse; exocytosis; hair cell; capacitance; Pax8

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Received Sept. 12, 2006; revised Jan. 19, 2007; accepted Jan. 19, 2007.

Correspondence should be addressed to Tobias Moser, InnerEarLab, Department of Otolaryngology, University of Göttingen, Center for Molecular Physiology of the Brain, Bernstein Center for Computational Neuroscience, 37099 Göttingen, Germany. Email: tmoser{at}gwdg.de

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