Metabotropic glutamate receptors modulate glutamatergic and GABAergic synaptic transmission in the central nucleus of the inferior colliculus

Abstract

Fast glutamatergic and GABAergic transmission in the central nucleus of the inferior colliculus (ICC), a major auditory midbrain structure, is mediated respectively by alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid (AMPA) and γ-aminobutyric acid (GABA) A receptors. In this study, we used whole-cell patch clamp recordings in brain slices to investigate the effects of activation of metabotropic glutamate receptors (mGluRs) on synaptic responses mediated by AMPA and GABA A receptors in ICC neurons of young rats. Excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) mediated respectively by AMPA and GABA A receptors were elicited by stimulation of the lateral lemniscus, the major afferent pathway to the ICC. The agonists for groups I and II mGluRs, (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD), and for group III mGluRs, l-2-amino-3-hydroxypropanoic acid 3-phosphate ( l-SOP), did not affect intrinsic membrane properties of the ICC neurons. The agonist for group II mGluRs, (1 R,4 R,5 S,6 R)-4-amino-2-oxabicyclo[3.1.0] hexane-4,6-dicarboxylic acid (LY379268), significantly reduced the AMPA receptor-mediated EPSCs and GABA A receptor-mediated IPSCs. The effects were reversed by the group II mGluR antagonist, (2 S)-2-amino-2-[(1 S,2 S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495). The agonists for groups I and III, ( RS)-3,5-dihydroxyphenylglycine (DHPG) and l-SOP, respectively, did not affect AMPA or GABA A receptor-mediated responses. The reduction of the synaptic responses by LY379268 was accompanied by a substantial increase in a ratio of the second to the first AMPA receptor-mediated EPSCs and GABA A receptor-mediated IPSCs to paired-pulse stimulation. The results suggest that group II mGluRs regulate both fast glutamatergic and GABAergic synaptic transmission in the ICC, probably through a presynaptic mechanism due to reduction of transmitter release.