METABOTROPIC GLUTAMATE-RECEPTOR ACTIVATION MODULATES SOUND LEVEL PROCESSING IN THE COCHLEAR NUCLEUS

The principal role of ionotropic glutamate receptors in the transmissi on and processing of information in the auditory pathway has been inve stigated extensively. In contrast, little is known about the functiona l contribution of the G-protein-coupled metabotropic glutamate recepto rs (mGluRs), although their anatomic location suggests that they exerc ise a significant influence on auditory processing. To investigate thi s issue, sound-evoked responses were obtained from single auditory neu rons in the cochlear nuclear complex of anesthetized cats and gerbils, and metabotropic ligands were administered locally through microionop horetic pipettes. In general, microionophoresis of the mGluR agonists, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S,1'S,2'S)-2-( carboxycyclopropyl) glycine, initially produced a gradual increase in spontaneous and sound-evoked discharge rates. However, activation and recovery times were significantly longer than those observed for ionot ropic agonists, such as N-methyl-D-aspartate or lpha-amino-3-hydroxy-5 -methyl-4-isoxazolepropionic acid, consistent with the recruitment of a second-messenger system. The efficacy of mGluR agonists was diminish ed after administration of the mGluR antagonist, (+)-alpha-methyl-4-ca rboxyphenylglycine, consistent with a selective action at metabotropic recognition sites. In contrast, two distinct changes were observed af ter the mGluR agonist had been discontinued for several minutes. Appro ximately 50% of neurons exhibited a chronic depression of sound-evoked discharge rate reminiscent of long-term depression, a cellular proper ty observed in other systems. Approximately 30% of neurons exhibited a longlasting enhancement of the sound-evoked response similar to the c ellular phenomenon of long-term potentiation. These findings suggest t hat mGluR activation has a profound influence on the gain of primary a fferent driven activity in the caudal cochlear nucleus.