Group I metabotropic glutamate receptors generate two types of intrinsic membrane oscillations in hippocampal oriens/alveus interneurons

Gubbi Govindaiah, Young Jin Kang, Hannah Elisabeth Smashey Lewis, Leeyup Chung, Ethan M. Clement, Lazar John Greenfield, Edgar Garcia-Rill, Sang Hun Lee

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

GABAergic interneurons in the hippocampus are critically involved in almost all hippocampal circuit functions including coordinated network activity. Somatostatin-expressing oriens-lacunosum moleculare (O-LM) interneurons are a major subtype of dendritically projecting interneurons in hippocampal subregions (e.g., CA1), and express group I metabotropic glutamate receptors (mGluRs), specifically mGluR 1 and mGluR 5 . Group I mGluRs are thought to regulate hippocampal circuit functions partially through GABAergic interneurons. Previous studies suggest that a group I/II mGluR agonist produces slow supra-threshold membrane oscillations (<0.1 Hz), which are associated with high-frequency action potential (AP) discharges in O-LM interneurons. However, the properties and underlying mechanisms of these slow oscillations remain largely unknown. We performed whole-cell patch-clamp recordings from mouse interneurons in the stratum oriens/alveus (O/A interneurons) including CA1 O-LM interneurons. Our study revealed that the selective mGluR 1/5 agonist (S)-3,5-dihydroxyphenylglycine (DHPG) induced slow membrane oscillations (<0.1 Hz), which were associated with gamma frequency APs followed by AP-free perithreshold gamma oscillations. The selective mGluR 1 antagonist (S)-(+)-α-Amino-4-carboxy-2-methylbenzeneacetic acid (LY367385) reduced the slow oscillations, and the selective mGluR 5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) partially blocked them. Blockade of nonselective cation-conducting transient receptor potential channels, L-type Ca 2+ channels, or ryanodine receptors all abolished the slow oscillations, suggesting the involvement of multiple mechanisms. Our findings suggest that group I mGluR activation in O/A interneurons may play an important role in coordinated network activity, and O/A interneuron vulnerability to excitotoxicity, in disease states like seizures, is at least in part due to an excessive rise in intracellular Ca 2+ .

Original languageEnglish
Pages (from-to)150-162
Number of pages13
JournalNeuropharmacology
Volume139
DOIs
StatePublished - Sep 1 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Ltd

Keywords

  • Excitotoxicity
  • Metabotropic glutamate receptors
  • Perithreshold membrane oscillations
  • Seizures
  • Somatostatin-expressing interneurons

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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