Elevated auditory brainstem response thresholds in mice with Connexin36 gene ablation

Abstract

Conclusion: Expression of connexin36 (Cx36) and electrical synapses formed by Cx36-containing gap junctions contribute to normal auditory brainstem response thresholds in mice. Objectives: Electrical synaptic transmission mediated by gap junctions has not been intensively studied in the auditory system. This study used transgenic mice with knockout of the gene coding for the major protein that forms neuronal gap junctions in mammalian brain (Cx36) to evaluate the role of Cx36 in murine hearing. Methods: Auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAEs) were measured in 26 wild-type and 26 Cx36 knockout mice. ABR thresholds were used to assess auditory brainstem function at four frequencies. DPOAEs were delivered for seven frequency pairs to assess cochlear function. Results: The magnitudes of the 2f1–f2 distortion products were not different between Cx36 knockout and wild-type mice, suggesting similar cochlear function in the two groups. ABR thresholds were significantly elevated in the Cx36 knockout compared with the wild-type groups, suggesting impaired function in the auditory brainstem. The results suggest that electrical synapses formed by Cx36-containing gap junctions contribute to auditory sound processing and function at the level of the brainstem, not the cochlea. These findings may be important for understanding human auditory pathology.

Keywords:

• distortion product otoacoustic emissions
• electrical synapses
• gap junctions
• hearing deficiencies
• neurons

Acknowledgments

This work was supported by funds from the Department of Otolaryngology, University of Manitoba, and by Science Without Borders provided to BWB, and by grants from the Canadian Institutes of Health Research and the Natural Science and Engineering Council to JIN. We thank Dr B. D. Lynn for help with genotyping transgenic mice, and Dr D. Paul (Harvard University) for generously providing breeding pairs of Cx36 knockout and wild-type mice. Presented at the 2014 Annual meeting of The Collegium Oto-Rhino-Laryngologicum Amicitiae Sacrum (CORLAS) in Istanbul, Turkey, August 26, 2014.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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