mGluRs modulate gustatory inputs 1 Group III Metabotropic Glutamate Receptors (mGluRs) Modulate Transmission of Gustatory Inputs in the Brainstem

Glutamate is the principal neurotransmitter at the primary sensory afferent synapse in the medulla for the taste system. At this synapse, glutamate activates NMDA and nonNMDA (AMPA and Kainate) ionotropic receptors to effect a response in the secondorder neurons. The current experiment is the first to examine the role of metabotropic glutamate receptors (mGluR) in the transmission of taste information. In an in vitro slice preparation of the primary vagal gustatory nucleus in goldfish, primary gustatory afferent fibers were stimulated electrically, while evoked dendritic field potentials were recorded in the sensory layers. Recordings were made before, during, and after bath application of mGluR agonists for various mGluR groups and subtypes. Whereas a group III agonist (L-2-amino-4-phosphonobutanoate; L-AP4) reduced the field potential, group I and II agonists had no effect. Furthermore, the selective mGluR4 agonist (3RS, 4RS)-1aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-III) and mGluR8 agonist, (RS)-4phosphonophenylglycine (PPG), were effective at reducing the field potential, while agonists selective for mGluR6 and 7 were not. A group III mGluR antagonist ((S)-2Amino-2-methyl-4-phosphonobutanoic acid; MAP4) attenuated frequency-dependent depression, indicating that endogenous glutamate binds to presynaptic mGluRs under normal conditions. Furthermore, PCR showed that mRNA for mGluR4 and 8 are expressed in the vagal ganglia, a prerequisite if those receptors are expressed presynaptically in the vagal lobe. Collectively, these experiments indicate that mGluR4 and 8 are presynaptic at the primary gustatory afferent synapse and that their activation inhibits glutamatergic release.