title: Hyperexcitability of rat thalamocortical networks after exposure to general anesthesia during brain development.
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.
authors: Department of Anesthesiology, Neuroscience Graduate Program.
authors: Michael R
authors: MR
authors: DiGruccio
authors: Department of Anesthesiology, Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors: Srdjan
authors: S
authors: Joksimovic
authors: Department of Anesthesiology.
authors: Pavle M
authors: PM
authors: Joksovic
authors: Department of Anesthesiology.
authors: Nadia
authors: N
authors: Lunardi
authors: Department of Anesthesiology.
authors: Reza
authors: R
authors: Salajegheh
authors: Department of Anesthesiology, Neuroscience Graduate Program, Neuroscience.
authors: Vesna
authors: V
authors: Jevtovic-Todorovic
authors: Neuroscience Graduate Program, Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, and.
authors: Mark P
authors: MP
authors: Beenhakker
authors: Neuroscience Graduate Program, Departments of Neurology, Neuroscience, Pediatrics, and.
authors: Howard P
authors: http://orcid.org/0000-0003-0528-4949
authors: HP
authors: Goodkin
authors: Department of Anesthesiology, Neuroscience Graduate Program, Neuroscience, st9d@virginia.edu.
authors: Slobodan M
authors: SM
authors: Todorovic
mesh_terms: D015107:4-Butyrolactone / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000768:Anesthesia, General; D000818:Animals; D000831:Animals, Newborn; D001549:Benzamides / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development
chemical_list: C570743:3,5-dichloro-N-(1-(2,2-dimethyltetrahydropyran-4-ylmethyl)-4-fluoropiperidin-4-ylmethyl)benzamide; D001549:Benzamides; D002121:Calcium Channel Blockers; D010880:Piperidines; D015107:4-Butyrolactone
keywords: GABAA receptor; T-channels; anesthesia; glutamate; low-voltage-activated; thalamus
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