title: Early Exposure to General Anesthesia with Isoflurane Downregulates Inhibitory Synaptic Neurotransmission in the Rat Thalamus.
abstract: Recent evidence supports the idea that common general anesthetics (GAs) such as isoflurane (Iso) and nitrous oxide (N2O; laughing gas) are neurotoxic and may harm the developing mammalian brain, including the thalamus; however, to date very little is known about how developmental exposure to GAs may affect synaptic transmission in the thalamus which, in turn, controls the function of thalamocortical circuitry. To address this issue we used in vitro patch-clamp recordings of evoked inhibitory postsynaptic currents (eIPSCs) from intact neurons of the nucleus reticularis thalami (nRT) in brain slices from rat pups (postnatal age P10-P18) exposed at age of P7 to clinically relevant GA combinations of Iso and N2O. We found that rats exposed to a combination of 0.75 % Iso and 75 % N2O display lasting reduction in the amplitude and faster decays of eIPSCs. Exposure to sub-anesthetic concentrations of 75 % N2O alone or 0.75 % Iso alone at P7 did not affect the amplitude of eIPSCs; however, Iso alone, but not N2O, significantly accelerated decay of eIPSCs. Anesthesia with 1.5 % Iso alone decreased amplitudes, caused faster decay and decreased the paired-pulse ratio of eIPSCs. We conclude that anesthesia at P7 with Iso alone or in combination with N2O causes plasticity of eIPSCs in nRT neurons by both presynaptic and postsynaptic mechanisms. We hypothesize that changes in inhibitory synaptic transmission in the thalamus induced by GAs may contribute to altered neuronal excitability and consequently abnormal thalamocortical oscillations later in life.
authors.affiliation: Department of Anesthesiology, University of Virginia School of Medicine, PO 800710, Charlottesville, VA, 22908-0710, USA.
authors.forename: Pavle M
authors.initials: PM
authors.lastname: Joksovic
authors.forename: Nadia
authors.initials: N
authors.lastname: Lunardi
authors.forename: Vesna
authors.initials: V
authors.lastname: Jevtovic-Todorovic
authors.forename: Slobodan M
authors.initials: SM
authors.lastname: Todorovic
mesh_terms: D000769:Anesthesia, Inhalation / Q000009:adverse effects*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D004357:Drug Synergism; D004558:Electric Stimulation; D005260:Female; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D007530:Isoflurane / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron; D008874:Midazolam / Q000008:administration & dosage / Q000633:toxicity; D009410:Nerve Degeneration / Q000139:chemically induced; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009609:Nitrous Oxide / Q000008:administration & dosage / Q000633:toxicity; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000648:ultrastructure; D020651:Ventral Thalamic Nuclei / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D009609:Nitrous Oxide; D008874:Midazolam