title: Activation of GIRK channels by muscarinic receptors and group II metabotropic glutamate receptors suppresses Golgi cell activity in the cochlear nucleus of mice.
abstract: Granule cells and parallel fiber circuits in the dorsal cochlear nucleus (DCN) play a role in integration of multimodal sensory with auditory inputs. The activity of granule cells is regulated through inhibitory connections made by Golgi cells. Golgi cells in turn probably receive parallel fiber inputs and regulate activity of the DCN. We have investigated the electrophysiological properties of Golgi cells using the whole cell patch-clamp method in slices made from transgenic mice that express green fluorescent protein driven by the promotor of metabotropic glutamate receptor subtype 2. Stimulation of auditory nerve fibers (ANFs) and of parallel fibers evoked glutamatergic excitatory postsynaptic currents (EPSC) through AMPA receptors. The strengths and latencies of these inputs differed, however. ANF stimulation evoked EPSCs after 4.7 +/- 0.4 ms, whereas parallel fiber stimulation evoked EPSCs after 1.4 +/- 0.2 ms that were on average 2.5 times as large. The multiple peaks and prolonged activity suggest the presence of polysynaptic connections between ANFs and Golgi cells. Agonists for group II metabotropic glutamate receptors (mGluRs) and for muscarinic receptors induced membrane hyperpolarization and suppressed the firing of Golgi cells by activating G-protein-coupled inward rectifier K(+) (GIRK) channels. These results strongly suggest that Golgi cells were regulated through the combined activities of glutamatergic and cholinergic synapses, which presumably regulated the temporal firing patterns of granule cells and through them the activity of principal cells of the DCN.
authors.affiliation: Department of Physiology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Irie
authors.forename: Iwao
authors.initials: I
authors.lastname: Fukui
authors.forename: Harunori
authors.initials: H
authors.lastname: Ohmori
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology; D017626:Cochlear Nucleus / Q000166:cytology* / Q000502:physiology*; D025802:Electric Capacitance; D017097:Electric Impedance; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000502:physiology; D009415:Nerve Net / Q000502:physiology*; D018408:Patch-Clamp Techniques; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000235:genetics / Q000502:physiology*; D050494:Vesicular Acetylcholine Transport Proteins / Q000502:physiology
chemical_list: D018679:Cholinergic Agonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D053645:Interleukin-2 Receptor alpha Subunit; D018094:Receptors, Metabotropic Glutamate; D011976:Receptors, Muscarinic; D050494:Vesicular Acetylcholine Transport Proteins; C108822:metabotropic glutamate receptor 2; D049452:Green Fluorescent Proteins