Group I metabotropic glutamate receptors in spiral ganglion neurons contribute to excitatory neurotransmissions in the cochlea.
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.[1]References
- Group I metabotropic glutamate receptors in spiral ganglion neurons contribute to excitatory neurotransmissions in the cochlea. Peng, B.G., Li, Q.X., Ren, T.Y., Ahmad, S., Chen, S.P., Chen, P., Lin, X. Neuroscience (2004) [Pubmed]
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