Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses

L. Klotz, O. Wendler, R. Frischknecht, R. Shigemoto, H. Schulze, R. Enz, FASEB Journal 33 (2019) 13734–13746.

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Journal Article | Published | English
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Abstract
Glutamate is the major excitatory neurotransmitter in the CNS binding to a variety of glutamate receptors. Metabotropic glutamate receptors (mGluR1 to mGluR8) can act excitatory or inhibitory, depending on associated signal cascades. Expression and localization of inhibitory acting mGluRs at inner hair cells (IHCs) in the cochlea are largely unknown. Here, we analyzed expression of mGluR2, mGluR3, mGluR4, mGluR6, mGluR7, and mGluR8 and investigated their localization with respect to the presynaptic ribbon of IHC synapses. We detected transcripts for mGluR2, mGluR3, and mGluR4 as well as for mGluR7a, mGluR7b, mGluR8a, and mGluR8b splice variants. Using receptor-specific antibodies in cochlear wholemounts, we found expression of mGluR2, mGluR4, and mGluR8b close to presynaptic ribbons. Super resolution and confocal microscopy in combination with 3-dimensional reconstructions indicated a postsynaptic localization of mGluR2 that overlaps with postsynaptic density protein 95 on dendrites of afferent type I spiral ganglion neurons. In contrast, mGluR4 and mGluR8b were expressed at the presynapse close to IHC ribbons. In summary, we localized in detail 3 mGluR types at IHC ribbon synapses, providing a fundament for new therapeutical strategies that could protect the cochlea against noxious stimuli and excitotoxicity.
Publishing Year
Date Published
2019-12-01
Journal Title
FASEB journal
Volume
33
Issue
12
Page
13734-13746
eISSN
IST-REx-ID

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Klotz L, Wendler O, Frischknecht R, Shigemoto R, Schulze H, Enz R. Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses. FASEB journal. 2019;33(12):13734-13746. doi:10.1096/fj.201901543R
Klotz, L., Wendler, O., Frischknecht, R., Shigemoto, R., Schulze, H., & Enz, R. (2019). Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses. FASEB Journal, 33(12), 13734–13746. https://doi.org/10.1096/fj.201901543R
Klotz, Lisa, Olaf Wendler, Renato Frischknecht, Ryuichi Shigemoto, Holger Schulze, and Ralf Enz. “Localization of Group II and III Metabotropic Glutamate Receptors at Pre- and Postsynaptic Sites of Inner Hair Cell Ribbon Synapses.” FASEB Journal 33, no. 12 (2019): 13734–46. https://doi.org/10.1096/fj.201901543R.
L. Klotz, O. Wendler, R. Frischknecht, R. Shigemoto, H. Schulze, and R. Enz, “Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses,” FASEB journal, vol. 33, no. 12, pp. 13734–13746, 2019.
Klotz L, Wendler O, Frischknecht R, Shigemoto R, Schulze H, Enz R. 2019. Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses. FASEB journal. 33(12), 13734–13746.
Klotz, Lisa, et al. “Localization of Group II and III Metabotropic Glutamate Receptors at Pre- and Postsynaptic Sites of Inner Hair Cell Ribbon Synapses.” FASEB Journal, vol. 33, no. 12, FASEB, 2019, pp. 13734–46, doi:10.1096/fj.201901543R.

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