Newly Published
Perioperative Medicine  |   September 2017
Disruption of Hippocampal Multisynaptic Networks by General Anesthetics
Author Notes
  • From the Department of Physiology and Pharmacology (M.-C.K.) and the Department of Physiology and Pharmacology and Program in Neuroscience (L.S.L.), The University of Western Ontario, London, Ontario, Canada.
  • Submitted for publication March 1, 2017. Accepted for publication August 1, 2017.
    Submitted for publication March 1, 2017. Accepted for publication August 1, 2017.×
  • Research Support: This research was supported by the Canadian Institutes of Health Research (grant No. MOP-15685), Ottawa, Ontario, Canada, and the Natural Sciences and Engineering Research Council (grant No. 1037–2008), Ottawa, Ontario, Canada.
    Research Support: This research was supported by the Canadian Institutes of Health Research (grant No. MOP-15685), Ottawa, Ontario, Canada, and the Natural Sciences and Engineering Research Council (grant No. 1037–2008), Ottawa, Ontario, Canada.×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Leung: Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario N6A5C1, Canada. sleung@uwo.ca. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Central and Peripheral Nervous Systems / Pharmacology
Perioperative Medicine   |   September 2017
Disruption of Hippocampal Multisynaptic Networks by General Anesthetics
Anesthesiology Newly Published on September 14, 2017. doi:10.1097/ALN.0000000000001861
Anesthesiology Newly Published on September 14, 2017. doi:10.1097/ALN.0000000000001861
Abstract

Background: Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function.

Methods: Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Spontaneous local field potentials and evoked field potentials were recorded in freely behaving rats before (baseline) and after various doses of isoflurane (0.25 to 1.5%) and sodium pentobarbital (10 mg/kg intraperitoneal).

Results: Monosynaptic population excitatory postsynaptic potentials at the basal and apical dendrites of CA1 were significantly decreased at greater than or equal to 0.25% (n = 4) and greater than or equal to 1.0% (n = 6) isoflurane, respectively. The perforant path evoked multisynaptic response at CA1 was decreased by ~50% at greater than or equal to 0.25% isoflurane (n = 5). A decreased population excitatory postsynaptic potential was accompanied by increased paired-pulse facilitation. Population spike amplitude in relation to apical dendritic population excitatory postsynaptic potential was not significantly altered by isoflurane. Spontaneous hippocampal local field potential at 0.8 to 300 Hz was dose-dependently suppressed by isoflurane (n = 6), with local field potential power in the 50- to 150-Hz band showing the highest decrease with isoflurane dose, commensurate with the decrease in trisynaptic CA1 response. Low-dose pentobarbital (n = 7) administration decreased the perforant path evoked trisynaptic CA1 response and hippocampal local field potentials at 78 to 125 Hz.

Conclusions: Hippocampal networks are sensitive to low doses of isoflurane and pentobarbital, possibly through both glutamatergic and γ-aminobutyric acid–mediated transmission. Network disruption could help explain the impairment of hippocampal-dependent cognitive functions with low-dose anesthetic.