title: Distinct modes of modulation of GABAergic transmission by Group I metabotropic glutamate receptors in rat entorhinal cortex.
abstract: Activation of metabotropic glutamate receptors (mGluRs) modulates synaptic transmission, whereas the roles of mGluRs in GABAergic transmission in the entorhinal cortex (EC) are elusive. Here, we examined the effects of mGluRs on GABAergic transmission onto the principal neurons in the superficial layers of the EC. Bath application of DHPG, a selective Group I mGluR agonist, increased the frequency and amplitude of spontaneous IPSCs (sIPSCs) whereas application of DCG-IV, an agonist for Group II mGluRs or L-AP4, an agonist for Group III mGluRs failed to change significantly sIPSC frequency and amplitude. Bath application of DHPG failed to change significantly the frequency and amplitude of miniature IPSCs (mIPSCs) recorded in the presence of tetradotoxin but significantly reduced the amplitude of IPSCs evoked by extracellular field stimulation or in synaptically connected interneuron-pyramidal neuron pairs in layer III of the EC. DHPG increased the frequency but reduced the amplitude of APs recorded from entorhinal interneurons. Bath application of DHPG generated membrane depolarization and increased the input resistance of GABAergic interneurons. DHPG-mediated depolarization of GABAergic interneurons was mediated by inhibition of background K(+) channels which are insensitive to extracellular Cs(+), TEA, 4-AP, and Ba(2+). DHPG-induced facilitation of sIPSCs was mediated by mGluR(5) and required the function of Galphaq but was independent of phospholipase C activity. Elevation of synaptic glutamate concentration by bath application of glutamate transporter inhibitors significantly increased sIPSC frequency and amplitude demonstrating a physiological role of mGluRs in GABAergic transmission. Our results provide a cellular and molecular mechanism to explain the physiological and pathological roles of mGluRs in the EC.
authors.affiliation: Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota 58203, USA.
authors.forename: Pan-Yue
authors.initials: PY
authors.lastname: Deng
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Xiao
authors.forename: Saobo
authors.initials: S
authors.lastname: Lei
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D018728:Entorhinal Cortex / Q000166:cytology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000145:classification / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010648:Phenylacetates / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C107349:2-chloro-5-hydroxyphenylglycine; D000927:Anticonvulsants; D001565:Benzoates; D002316:Cardiotonic Agents; D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; D010648:Phenylacetates; D026902:Potassium Channel Blockers; D011743:Pyrimidines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C082246:ICI D2788; C079694:alpha-methyl-4-carboxyphenylglycine; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D008734:Methoxyhydroxyphenylglycol; D005680:gamma-Aminobutyric Acid; D019789:Tetraethylammonium; C079693:4-carboxyphenylglycine; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol