Optical Stimulation of Thalamic Spindle Circuitry Sustains Electroencephalogram Patterns of General Anesthesia but not Duration of Loss of Consciousness.

Autor: Mesbah-Oskui L; Department of Medicine, Queen's University, Kingston, Ontario K7L 3N6, Canada., Gurges P; Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A8, Canada., Liu WY; Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A8, Canada; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Department of Pharmacology, School of Basic Medical Science, Fudan University, Shanghai 200032, China., Horner RL; Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Electronic address: richard.horner@utoronto.ca.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2021 Aug 01; Vol. 468, pp. 110-122. Date of Electronic Publication: 2021 Jun 12.
DOI: 10.1016/j.neuroscience.2021.06.009
Abstrakt: Alterations in thalamic GABAergic signaling are implicated in mediating the rise in 12-30 Hz electroencephalogram (EEG) activity that signals anesthetic-induced loss-of-consciousness with GABA A receptor-targeting general anesthetics. A number of modeling studies have identified that anesthetic-induced alterations in thalamocortico-corticothalamic signaling in the same network that generates sleep spindles would be sufficient to elicit this key EEG signature of anesthetic hypnosis with general anesthetic agents. Accordingly, we hypothesize that targeted stimulation of this thalamic GABAergic circuitry into a sleep-spindle mode of activity would promote the general anesthetic effects of etomidate. We recorded EEG activity and loss-of-righting reflex in transgenic mice expressing channel rhodopsin-2 on GABAergic neurons (ChR2-VGAT, n = 8) and control, wild-type mice (C57BL/6J, n = 8). On two consecutive days mice were randomly assigned to receive spindle-rhythm stimulation via an optical probe targeting the left reticular thalamic nucleus or no stimulation. After an initial 30-minute recording, mice were administered etomidate (12 mg/kg, intraperitoneal) and recorded for 90 min with or without optical stimulation. Etomidate elicited an increase in 12-30 Hz EEG power in wild-type and ChR2-VGAT mice for 20 min following administration (p < 0.001). Optical spindle-rhythm stimulation prolonged the increase in 12-30 Hz activity in ChR2-VGAT mice only (p = 0.023). Spindle-rhythm stimulation also increased the incidence and duration of sleep spindle-like oscillations in ChR2-VGAT mice only (all p ≤ 0.001). Despite the maintained anesthetic-like changes in EEG activity, optical spindle-rhythm stimulation was not associated with changes in the time to and duration of the loss-of-righting reflex, a behavioral endpoint of etomidate-induced general anesthesia in rodents.
(Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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