Elsevier

Neuroscience

Volume 123, Issue 1, 2004, Pages 221-230
Neuroscience

Group i metabotropic glutamate receptors in spiral ganglion neurons contribute to excitatory neurotransmissions in the cochlea

https://doi.org/10.1016/j.neuroscience.2003.09.010Get rights and content

Abstract

Evidence has accumulated over the years supporting glutamate as the primary neurotransmitter used by hair cells in afferent cochlear neurotransmission. Besides acting on ionotropic glutamate receptors, glutamate also activates second messenger systems via G-protein-coupled metabotropic glutamate receptors (mGluRs) to modulate neuronal excitability. However, it is unclear whether mGluRs participate in cochlear neurotransmission. We present evidence directly supporting a functional role for group I metabotropic glutamate receptors (mGluRIs) in spiral ganglion (SG) neurons. The presence of mGluRI and downstream G-protein subunits was demonstrated by molecular biology and immunolabeling methods. Direct activation of mGluRIs in cultured SG neurons resulted in transient increases of intracellular Ca++ concentration and transient inward currents that gave rise to firings of multiple action potentials. These responses showed mGluRI pharmacological specificity and quickly desensitized. We next examined changes in cochlear function after noise exposure as a result of pharmacologically manipulating cochlear glutamate neurotransmission. These in vivo tests showed that blocking non-N-methyl-d-aspartic acid glutamate receptors was sufficient to eliminate compound action potentials of the auditory nerve, and pharmacologically inhibiting mGluRIs in the cochlea did not significantly affect the hearing threshold. In contrast, blocking mGluRIs lowered the amplitude of compound action potentials at louder sound levels and reduced the noise-induced temporary threshold shift. Our results suggest that although mGluRIs did not initiate fast excitatory cochlear neurotransmission, their activation contributed to the growth of excitatory responses of the cochlea. As a result, the cochlea was more resistant to noise-induced temporary hearing losses without the activation of mGluRIs in SG neurons.

Section snippets

Detection and relative quantification of mGluRIs and G-protein subunits in the cochlea by real-time reverse transcription (RT), polymerase chain reaction (PCR) amplification and cDNA-macroarray

After being anesthetized by ketamine (80 mg/kg; Phoenix Pharmaceutical Inc., St. Joseph, MO, USA) and xylazine (10 mg/kg; Lloyd Laboratories, Shenandoah, IA, USA), mice (strain CD-1) were killed by decapitation. The animal use protocol was approved by the institutional animal use and care committee (IACUC) of the House Ear Institute. All experiments conformed to the international guidelines on the ethical use of animals, and the IACUC ensured that the number of animals used and their suffering

Mgluris and multiple types of g-protein subunits were expressed in the cochlea. immunolabeling showed that a subset of sg neurons expressed mglur1

We first detected the presence of mGluRIs in the cochlea by RT-PCR amplifications. Starting with the same amount of cochlear RNA, mGluR1 and mGluR5 were amplified to a level above the noise floor after about 18 amplification cycles (Fig. 1A). The growth of mGluR5 amplicon lagged significantly behind that of mGluR1. Measured at their respective linear increasing phases on a semi-log scale, as indicated by a horizontal dashed line in Fig. 1, Fig. 4. 9 more PCR cycles were needed for mGluR5 to

Acknowledgements

This study was supported by grants from NIDCD (NIH RO1 04709 and R21 DC04492).

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