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+ .
|Number of pages||13|
|State||Published - Sep 1 2018|
Bibliographical noteFunding Information:
This work was supported by the College of Medicine , University of Arkansas for Medical Sciences to S-HL, Bogard Neurology Research and Stroke Prevention Fund to S-HL, and Core Facilities of the Center for Translational Neuroscience , Award P30 GM110702 from the IDeA program at NIGMS to EGR.
This work was supported by the College of Medicine, University of Arkansas for Medical Sciences to S-HL, Bogard Neurology Research and Stroke Prevention Fund to S-HL, and Core Facilities of the Center for Translational Neuroscience, Award P30 GM110702 from the IDeA program at NIGMS to EGR.
© 2018 Elsevier Ltd
- Metabotropic glutamate receptors
- Perithreshold membrane oscillations
- Somatostatin-expressing interneurons
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience