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Articles, Cellular/Molecular

Hyperexcitability of Rat Thalamocortical Networks after Exposure to General Anesthesia during Brain Development

Michael R. DiGruccio, Srdjan Joksimovic, Pavle M. Joksovic, Nadia Lunardi, Reza Salajegheh, Vesna Jevtovic-Todorovic, Mark P. Beenhakker, Howard P. Goodkin and Slobodan M. Todorovic
Journal of Neuroscience 28 January 2015, 35 (4) 1481-1492; DOI: https://doi.org/10.1523/JNEUROSCI.4883-13.2015
Michael R. DiGruccio
1Department of Anesthesiology,
2Neuroscience Graduate Program,
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Srdjan Joksimovic
1Department of Anesthesiology,
7Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
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Pavle M. Joksovic
1Department of Anesthesiology,
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Nadia Lunardi
1Department of Anesthesiology,
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Reza Salajegheh
1Department of Anesthesiology,
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Vesna Jevtovic-Todorovic
1Department of Anesthesiology,
2Neuroscience Graduate Program,
4Neuroscience,
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Mark P. Beenhakker
2Neuroscience Graduate Program,
6Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, and
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Howard P. Goodkin
2Neuroscience Graduate Program,
3Departments of Neurology,
4Neuroscience,
5Pediatrics, and
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Slobodan M. Todorovic
1Department of Anesthesiology,
2Neuroscience Graduate Program,
4Neuroscience,
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Abstract

Prevailing literature supports the idea that common general anesthetics (GAs) cause long-term cognitive changes and neurodegeneration in the developing mammalian brain, especially in the thalamus. However, the possible role of GAs in modifying ion channels that control neuronal excitability has not been taken into consideration. Here we show that rats exposed to GAs at postnatal day 7 display a lasting reduction in inhibitory synaptic transmission, an increase in excitatory synaptic transmission, and concomitant increase in the amplitude of T-type calcium currents (T-currents) in neurons of the nucleus reticularis thalami (nRT). Collectively, this plasticity of ionic currents leads to increased action potential firing in vitro and increased strength of pharmacologically induced spike and wave discharges in vivo. Selective blockade of T-currents reversed neuronal hyperexcitability in vitro and in vivo. We conclude that drugs that regulate thalamic excitability may improve the safety of GAs used during early brain development.

  • anesthesia
  • GABAA receptor
  • glutamate
  • low-voltage-activated
  • T-channels
  • thalamus
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The Journal of Neuroscience: 35 (4)
Journal of Neuroscience
Vol. 35, Issue 4
28 Jan 2015
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Hyperexcitability of Rat Thalamocortical Networks after Exposure to General Anesthesia during Brain Development
Michael R. DiGruccio, Srdjan Joksimovic, Pavle M. Joksovic, Nadia Lunardi, Reza Salajegheh, Vesna Jevtovic-Todorovic, Mark P. Beenhakker, Howard P. Goodkin, Slobodan M. Todorovic
Journal of Neuroscience 28 January 2015, 35 (4) 1481-1492; DOI: 10.1523/JNEUROSCI.4883-13.2015

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Hyperexcitability of Rat Thalamocortical Networks after Exposure to General Anesthesia during Brain Development
Michael R. DiGruccio, Srdjan Joksimovic, Pavle M. Joksovic, Nadia Lunardi, Reza Salajegheh, Vesna Jevtovic-Todorovic, Mark P. Beenhakker, Howard P. Goodkin, Slobodan M. Todorovic
Journal of Neuroscience 28 January 2015, 35 (4) 1481-1492; DOI: 10.1523/JNEUROSCI.4883-13.2015
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Keywords

  • anesthesia
  • GABAA receptor
  • glutamate
  • low-voltage-activated
  • T-channels
  • thalamus

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