The critical role of persistent sodium current in hippocampal gamma oscillations. (1st January 2020)

• Record Type: Journal Article
• Authors: Kang, Young-Jin; Clement, Ethan M.; Sumsky, Stefan L.; Xiang, Yangfei; Park, In-Hyun; Santaniello, Sabato; Greenfield, Lazar John; Garcia-Rill, Edgar; Smith, Bret N.; Lee, Sang-Hun
• Is Part Of: Neuropharmacology. Volume 162(2020)
• Publication Date: 2020-01-01
• Subjects: Optogenetics -- Pyramidal-interneuron network gamma (PING) -- Parvalbumin-expressing interneurons -- Antiepileptic drugs -- Cognitive impairment; ACSF artificial cerebrospinal fluid -- AMPA α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid -- AP action potential -- APV 2-Amino-5-phosphonopentanoic acid -- CaMKII-alpha Ca2+/calmodulin-dependent protein kinase II-alpha -- ChR2 channelrhodopsin2 -- CGP55845 (2S)-3-[[(1S)-1-(3, 4-Dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl)phosphinic acid hydrochloride -- DIC differential interference contrast -- DMSO dimethyl sulfoxide -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- INaP persistent sodium current -- ING interneuron network gamma -- NBQX 2, 3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F) quinoxaline -- LFP local field potential -- NMDA N-methyl-d-aspartate -- PING pyramidal-interneuron network gamma -- PVBC parvalbumin-positive basket cell -- SR95531 6-Imino-3-(4-methoxyphenyl)-1(6H)-pyridazinebutanoic acid hydrobromide -- SWRs sharp wave-ripples -- TTX tetrodotoxin; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.107787
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Gamma network oscillations in the brain are fast rhythmic network oscillations in the gamma frequency range (~30-100 Hz), playing key roles in the hippocampus for learning, memory, and spatial processing. There is evidence indicating that GABAergic interneurons, including parvalbumin-expressing basket cells (PVBCs), contribute to cortical gamma oscillations through synaptic interactions with excitatory cells. However, the molecular, cellular, and circuit underpinnings underlying generation and maintenance of cortical gamma oscillations are largely elusive. Recent studies demonstrated that intrinsic and synaptic properties of GABAergic interneurons and excitatory cells are regulated by a slowly inactivating or non-inactivating sodium current ( i.e., persistent sodium current, I NaP ), suggesting that I NaP is involved in gamma oscillations. Here, we tested whether I NaP plays a role in hippocampal gamma oscillations using pharmacological, optogenetic, and electrophysiological approaches. We found that I NaP blockers, phenytoin (40 μM and 100 μM) and riluzole (10 μM), reduced gamma oscillations induced by optogenetic stimulation of CaMKII-expressing cells in CA1 networks. Whole-cell patch-clamp recordings further demonstrated that phenytoin (100 μM) reduced I NaP and firing frequencies in both PVBCs and pyramidal cells without altering threshold and amplitude of action potentials, but increased rheobase in both cell types. These results suggest that I NaP in pyramidal cells and PVBCs is required for hippocampal gamma oscillations, supporting a pyramidal-interneuron network gamma model. Phenytoin-mediated modulation of hippocampal gamma oscillations may be a mechanism underlying its anticonvulsant efficacy, as well as its contribution to cognitive impairments in epilepsy patients. Highlights: Phenytoin and riluzole reduce hippocampal gamma oscillations in the CA1 subregion. Phenytoin blocks I NaP in parvalbumin-expressing basket cells (PVBCs). Phenytoin increases rheobase and reduces firing frequency of PVBCs. Phenytoin blocks I NaP in pyramidal cells. Phenytoin increases rheobase and reduces firing frequency of pyramidal cells.